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  Session Start Time
Presentation Time
Location 		Pres #
& Type		 Poster Board # Authors & Institutions Abstract Title
Session # & Title
Sat 11/15 1:00 PM
1:00 PM - 2:00 PM

Washington Convention Center: Hall A-C 		27.5
Poster 		C3 *C. HILARIO-GOMEZ, A. NEWBY-KEW, A. RAISSI, S. PARADIS; Biol., Brandeis Univ., Waltham, MA The role of class 4 semaphorins in synapse formation

27.Synapse Dynamics and Molecular Signaling
Sat 11/15 1:00 PM
2:00 PM - 3:00 PM

Washington Convention Center: Hall A-C 		37.6
Poster 		H3 A. VEGA1,2, S. J. BIRREN2, *M. A. MORALES1; 1Dept Cell Biol & Physiol, Inst. Invest Biomedicas UNAM, Mexico, Mexico; 2Biol., Brandeis Univ., Waltham, MA Differential routing of VAChT and VMAT/NPY to separate projections of rat neonatal sympathetic neurons co-cultures with myocytes

37.Synaptic Transmission: Modulatory Mechanisms
Sat 11/15 1:00 PM
4:00 PM - 5:00 PM

Washington Convention Center: Hall A-C 		54.4
Poster 		Z29 *Y. C. ZHANG, J. LISMAN; Biol, Brandeis Univ., Waltham, MA A mechanism by which NMDA hypofunction, as may occur in schizophrenia, can produce thalamocortical dysrhythmia

54.Schizophrenia: Human Studies I
Sat 11/15 1:00 PM
2:00 PM - 3:00 PM

Washington Convention Center: Hall A-C 		64.6
Poster 		GG34 *D. NARAYANAN, S. NESELILER, D. KATZ, S. BIRREN; Neurosci., Brandeis Univ., Waltham, MA Role of cholinergic activity in taste learning in p75 knockout mice

64.Taste I
Sat 11/15 1:00 PM
4:00 PM - 5:00 PM

Washington Convention Center: Hall A-C 		64.8
Poster 		HH2 *B. F. SADACCA1, D. B. KATZ2; 1Biol., 2Psychology, Brandeis Univ., Waltham, MA Distributed processing of taste concentration

64.Taste I
Sat 11/15 1:00 PM
4:00 PM - 5:00 PM

Washington Convention Center: Hall A-C 		64.16
Poster 		HH10 *J. LV1, D. KATZ2, P. MILLER3; 1Dept. of Physics, 2Dept. of Psychology, 3Biol. and Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA Noise, oscillations and state sequences in a simple model of cortical sensory processing

64.Taste I
Sat 11/15 1:00 PM
1:00 PM - 2:00 PM

Washington Convention Center: Hall A-C 		64.17
Poster 		HH11 *T. YOSHIDA1, D. B. KATZ1,2; 1Dept Psychol, 2Volen Natl. Ctr. for Complex Systems, Brandeis Univ., Waltham, MA Neural activity during a taste discrimination task in rat gustatory cortex

64.Taste I
Sat 11/15 1:00 PM
4:00 PM - 5:00 PM

Washington Convention Center: Hall A-C 		91.8
Poster 		SS71 *M. BOURJAILY, P. MILLER; Brandeis Univ, Volen CCS, Waltham, MA Specificity versus associativity in associative based learning

91.Eye Blink Conditioning
Sun 11/16 8:00 AM
9:00 AM - 10:00 AM

Washington Convention Center: Hall A-C 		162.10
Poster 		GG1 *Y. FORTIS-SANTIAGO1, B. RODWIN1, D. B. KATZ2; 1Dept. of Biol., 2Psychology Dept., Brandeis Univ., Waltham, MA Olfactory learning requires the taste system

162.Multisensory Processing I
Sun 11/16 1:00 PM
3:30 PM - 3:45 PM

Washington Convention Center: Room 201 		218.11
Slide 		  *J. PEELLE1, V. TROIANI1, A. WINGFIELD2, M. GROSSMAN1; 1Dept. of Neurol., Univ. of Pennsylvania, Philadelphia, PA; 2Volen Natl. Ctr. for Complex Systems, Brandeis Univ., Waltham, MA Making up for lost sound: Hearing acuity modulates neural recruitment for speech comprehension in older adults

218.Human Aging
Sun 11/16 1:00 PM
1:30 PM - 1:45 PM

Washington Convention Center: Room 147B 		220.3
Slide 		  *H. M. FATHALLAH-SHAYKH1,2, J. BONA2, M. ROSBASH3, S. KADENER3; 1Dept Neurol Sci., Rush Univ. Med. Ctr., Chicago, IL; 2Mathematics, Univ. of Illinois at Chicago, Chicago, IL; 3Biol., Brandeis Univ., Waltham, MA New mathematical model of the drosophila circadian clock explains the paradoxical effects of clockwork orange mutation

220.Computation, Modeling, and Simulation I
Sun 11/16 1:00 PM
2:00 PM - 3:00 PM

Washington Convention Center: Hall A-C 		237.18
Poster 		D43 *T. M. SZABO1, T. BROOKINGS1, D. S. FABER2, T. PREUSS2; 1Biol Dept, Brandeis Univ., Waltham, MA; 2Domick P Purpura Dept of Neurosci., Albert Einstein Col. of Med., New York, NY Neurophysiological mechanisms underlying thermal acclimation in a neuron of the vertebrate central nervous system

237.Synaptic Integration II
Sun 11/16 1:00 PM
2:00 PM - 3:00 PM

Washington Convention Center: Hall A-C 		240.18
Poster 		E40 *M. N. MILLER, S. B. NELSON; Biol., Brandeis Univ., Waltham, MA Cell-type specific maintenance of neocortical firing type by network activity

240.Intrinsic Membrane Properties: Modulation of Neuronal Firing Properties by Inputs and Activity
Sun 11/16 1:00 PM
2:00 PM - 3:00 PM

Washington Convention Center: Hall A-C 		240.22
Poster 		F4 *M. E. LAMBO1, A. MAFFEI2, G. G. TURRIGIANO1; 1Biol., Brandeis Univ., Waltham, MA; 2Dept. of Neurobio. and Behavior, SUNY Stony Brook, Stony Brook, NY Monocular deprivation reduces the intrinsic excitability of layer 4 pyramidal neurons in binocular cortex

240.Intrinsic Membrane Properties: Modulation of Neuronal Firing Properties by Inputs and Activity
Sun 11/16 1:00 PM
3:00 PM - 4:00 PM

Washington Convention Center: Hall A-C 		240.23
Poster 		F5 *K. NATARAJ, G. TURRIGIANO; Dept Biol, Brandeis Univ., Waltham, MA Metaplasticity of intrinsic excitability of cortical layer 5 pyramidal neurons induced by visual deprivation

240.Intrinsic Membrane Properties: Modulation of Neuronal Firing Properties by Inputs and Activity
Sun 11/16 1:30 PM
2:35 PM - 2:55 PM

Washington Convention Center: Room 202B 		204.5
Minisymposium 		  D. Katz; Dept of Psychology, Brandeis Univ, Waltham, MA. Dynamics of Taste Responses

204.New Directions in Chemical Senses
Mon 11/17 8:00 AM
8:00 AM - 9:00 AM

Washington Convention Center: Hall A-C 		367.9
Poster 		JJ9 *P. A. DIZIO1,2, J. VENTURA1, J. KAPLAN1, I. SCHLEIFER1, M. LEHMANN1,3, J. R. LACKNER1,2; 1Ashton Graybiel Spatial Orientation Lab., 2Volen Ctr. for Complex Systems, 3Dept of Psychology, Brandeis Univ., Waltham, MA A method for parametric evaluation of angular path integration and dynamic spatial orientation

367.Vestibular System: Reflexes, Motor Control, and Perception
Mon 11/17 8:00 AM
9:00 AM - 10:00 AM

Washington Convention Center: Hall A-C 		379.14
Poster 		QQ50 *D. PIOVESAN1, A. PIEROBON1, P. DIZIO1,2, J. R. LACKNER1,2; 1Ashton Graybiel Lab., 2Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA Arm inertia matrix measured using impulse response

379.Control and Learning of Arm Movement I
Mon 11/17 8:00 AM
11:00 AM - 12:00 PM

Washington Convention Center: Hall A-C 		379.24
Poster 		QQ60 *A. M. TORRES1,2, P. DIZIO1,2, J. R. LACKNER1,2; 1Ashton Graybiel Lab., 2Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA Development of context-specific motor adaptation of object and limb dynamics in young children

379.Control and Learning of Arm Movement I
Mon 11/17 1:00 PM
2:45 PM - 3:00 PM

Washington Convention Center: Room 209A 		417.8
Slide 		  *Y. SHANG1, M. ROSBASH2; 1Dept Biol., Brandeis Univ., Waltham, MA; 2Dept Biol., Brandeis Univ/HHMI, Waltham, MA A function for the large PDF cells in Drosophila Arousal

417.Sleep: Systems and Behavior I
Mon 11/17 1:00 PM
4:00 PM - 5:00 PM

Washington Convention Center: Hall A-C 		422.12
Poster 		B38 B. W. OKATY, M. N. MILLER, K. SUGINO, C. M. HEMPEL, *S. B. NELSON; Dept Biol MS#008, Brandeis Univ., Waltham, MA Physiological and transcriptional maturation of a subtype of cortical GABAergic interneuron

422.Neuronal Differentiation: Activity-Dependent and Other Mechanisms
Mon 11/17 1:00 PM
1:00 PM - 2:00 PM

Washington Convention Center: Hall A-C 		447.5
Poster 		Y5 *V. S. DANI, S. B. NELSON; Biol. Dept., Brandeis Univ., Waltham, MA Synaptic dysfunction in Rett syndrome: studies in a mouse model

447.Rett Syndrome
Mon 11/17 1:00 PM
1:00 PM - 2:00 PM

Washington Convention Center: Hall A-C 		459.1
Poster 		FF2 *J. FISER1, M. CUI2, C. CHIU3, M. WELIKY4; 1Dept Psychol, Brandeis Univ., Waltham, MA; 2Psychology, Program in Cognitive Neurosci., Brandeis Universiy, MA; 3Neurosci., Albert Einstein Col. of Med., Bronx, NY; 4Brain and Cognitive Sci., Univ. of Rochester, Rochester, NY Characterizing internal dynamic states and their emergence in the primary visual cortex of the awake ferret

459.Neural Coding in the Visual System I
Mon 11/17 1:00 PM
4:00 PM - 5:00 PM

Washington Convention Center: Hall A-C 		459.12
Poster 		FF13 *B. L. WHITE, J. FISER; Brandeis Univ., Waltham, MA The relationship between awake and anesthetized neural responses in the primary visual cortex of the rat

459.Neural Coding in the Visual System I
Mon 11/17 5:15 PM
5:15 PM - 6:15 PM

Washington Convention Center: Hall D 		Presidential Special Lecture   L. C. GRIFFITH; Dept Biol MS008, Brandeis Univ., Waltham, MA Sleep: Studying a Human Behavior in an Insect

405.Sleep: Studying a Human Behavior in an Insect
Tue 11/18 8:00 AM
8:00 AM - 9:00 AM

Washington Convention Center: Hall A-C 		525.8
Poster 		B21 *C. E. TAFT, G. G. TURRIGIANO; Biol., Brandeis Univ., Waltham, MA GFP-CaMKII dynamics and phosphorylation in synaptic remodeling

525.Molecular Signaling at Synapses
Tue 11/18 8:00 AM
11:00 AM - 12:00 PM

Washington Convention Center: Hall A-C 		529.16
Poster 		C46 *B. K. BRACKEN, G. G. TURRIGIANO; Biol., Brandeis Univ., Waltham, MA Developmental and activity dependent regulation of TrkB receptor isoforms

529.Neurotrophins: Intracellular Signaling Cascades
Tue 11/18 8:00 AM
11:00 AM - 12:00 PM

Washington Convention Center: Hall A-C 		540.8
Poster 		L2 *M. A. GAINEY, J. R. HURVITZ-WOLFF, M. E. LAMBO, G. G. TURRIGIANO; Biol., Brandeis Univ., Waltham, MA Synaptic scaling requires the GluR2 subunit of the AMPA receptor

540.Homeostatic Synaptic Plasticity I
Tue 11/18 8:00 AM
10:00 AM - 11:00 AM

Washington Convention Center: Hall A-C 		540.15
Poster 		L9 *C. C. STEINMETZ1, G. G. TURRIGIANO2; 1Turrigiano Lab., 2Biol. Dept/Turrigiano Lab., Brandeis Univ., Waltham, MA TNFalpha is required for the maintenance but not induction of Synaptic Scaling

540.Homeostatic Synaptic Plasticity I
Tue 11/18 8:00 AM
9:00 AM - 10:00 AM

Washington Convention Center: Hall A-C 		574.14
Poster 		OO13 *R. GRASHOW, A.-E. TOBIN, E. MARDER; Biol. Dept, Brandeis Univ., Waltham, MA Serotonin alters the intrinsic membrane properties of gastric mill neurons in the crab C. borealis

574.Rhythmic Motor: Neuromodulation I
Tue 11/18 8:00 AM
10:00 AM - 11:00 AM

Washington Convention Center: Hall A-C 		574.15
Poster 		OO14 *M. FISEK1, L. S. TANG2, E. MARDER2; 1Biol., 2Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA Temperature-dependent cholinergic modulation of a small neural network

574.Rhythmic Motor: Neuromodulation I
Tue 11/18 1:00 PM
2:00 PM - 3:00 PM

Washington Convention Center: Hall A-C 		634.18
Poster 		E31 *J. A. LUTHER, S. BIRREN; Dept Biol, Brandeis Univ., Waltham, MA BDNF regulates neuron to neuron synaptic transmission in rat sympathetic neurons co-cultured with cardiac myocytes

634.Synaptic Modulation
Tue 11/18 1:00 PM
1:00 PM - 2:00 PM

Washington Convention Center: Hall A-C 		680.1
Poster 		RR30 B. C. WITTMANN1, G. TAN1, J. E. LISMAN2, R. J. DOLAN1, *E. DUZEL3; 1Wellcome Trust Ctr. for Neuroimaging, Univ. Col. London, London, United Kingdom; 2Brandeis Univ., Waltham, MA; 3Inst. Cognitive Neurosci., London, United Kingdom Striatal BOLD response and memory enhancement for cues predicting monetary wins and losses

680.Human Conditioning and Reward Learning
Wed 11/19 8:00 AM
8:00 AM - 9:00 AM

Washington Convention Center: Hall A-C 		760.1
Poster 		EE19 E. YU1, S. CHOI1, J. LISMAN2, *R. R. LLINAS1; 1Dept Physiol & Neurosci, New York Univ. Sch. Med., New York, NY; 2Dept Biol, Brandeis Univ., Waltham, MA NMDA-receptor block induced low frequency oscillations in the thalamocortical circuit: An in vitro voltage sensitive dye imaging study

760.Schizophrenia: Biochemical Studies
Wed 11/19 8:00 AM
11:00 AM - 12:00 PM

Washington Convention Center: Hall A-C 		760.24
Poster 		FF14 *Y. SERULLE1, F. J. URBANO2, J. E. LISMAN3, R. R. LLINAS1; 1Physiol. and Neurosci., NYU Sch. of Med., New York, NY; 2Inst. de Fisiología y Biología Mol. y Neurociencias (IFIBYNE), Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina; 3Dept. of Biol. and Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA Increase of oscillatory inhibitory synaptic events in thalamic relay neurons after inhibition of NMDA-mediated transmission

760.Schizophrenia: Biochemical Studies
Wed 11/19 8:00 AM
9:00 AM - 10:00 AM

Washington Convention Center: Hall A-C 		792.6
Poster 		TT54 *J. B. SLAWSON, E. A. KUKLIN, L. OSTROVSKY, L. C. GRIFFITH; Biol., Brandeis Univ., Waltham, MA Loss of dCASK produces a novel locomotor phenotype in Drosophila melanogaster

792.Learning and Memory: Insects
Wed 11/19 8:00 AM
8:00 AM - 9:00 AM

Washington Convention Center: Hall A-C 		793.13
Poster 		TT80 *S. M. WASSERMAN, D. BIRON, P. SENGUPTA; Brandeis Univ., Waltham, MA Communication among neurons in a thermosensory circuit in C. elegans

793.Learning and Memory: Invertebrates other than Insects and Aplysia
Wed 11/19 1:00 PM
2:30 PM - 2:45 PM

Washington Convention Center: Room 209A 		815.7
Slide 		  *T. PIQUADO, D. ISAACOWITZ, A. WINGFIELD; Brandeis Univ., Waltham, MA Effects of memory load, syntactic complexity and age on cognitive effort: a pupillometry study

815.Aging: Memory
Wed 11/19 1:00 PM
3:00 PM - 4:00 PM

Washington Convention Center: Hall A-C 		860.11
Poster 		JJ2 *P. PIGEON1, J. R. LACKNER1,2, P. DIZIO1,2; 1Ashton Graybiel Lab., 2Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA Immediate compensation for variations in self-generated Coriolis forces related to body dynamics and carried objects

860.Voluntary Movement: Cortical Planning and Execution VII
Wed 11/19 1:00 PM
3:00 PM - 4:00 PM

Washington Convention Center: Hall A-C 		861.3
Poster 		JJ17 *A. PIEROBON1, D. PIOVESAN1, P. DIZIO1,2, J. R. LACKNER1,2; 1Ashton Graybiel Lab., 2Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA Moving objects in microgravity

861.Control and Learning of Arm Movement II
Wed 11/19 1:00 PM
1:00 PM - 2:00 PM

Washington Convention Center: Hall A-C 		878.13
Poster 		SS63 *H. O. GALPERIN, B. L. WHITE, J. FISER; Brandeis Univ., Waltham, MA Expectation of reward modulates responses in rat primary visual cortex

878.Associative, Nonassociative, and Skill Learning




27.5/C3. The role of class 4 semaphorins in synapse formation
*C. HILARIO-GOMEZ, A. NEWBY-KEW, A. RAISSI, S. PARADIS;
Biol., Brandeis Univ., Waltham, MA
A critical question in the field of synapse formation is how a neuron matches the correct postsynaptic neurotransmitter receptors to the appropriate glutamatergic or GABAergic presynaptic terminal. Accumulating evidence suggests that the final specification of the postsynaptic structure as either glutamatergic or GABAergic occurs as a later step in synapse development. To begin to address this and other unresolved issues in synapse formation, we established an RNA interference (RNAi)-based screen in order to identify genes, in an unbiased manner, required for the development of synapses in cultured hippocampal neurons. In our initial screen, we uncovered a previously unknown role for two class 4 Semaphorin family members, Sema4B and Sema4D, in regulating glutamatergic and/or GABAergic synapse formation. Specifically, RNAi-mediated knockdown of Sema4B results in a decrease in both glutamatergic and GABAergic synapse density while RNAi-mediated knockdown of Sema4D results in a decrease in GABAergic synapse density without an apparent effect on glutamatergic synapse density. Interestingly, we found that both Sema4B and Sema4D are preferentially required for the proper formation of the postsynaptic specialization or glutamatergic and/or GABAergic synapses. We are using two parallel approaches to understand the role of Sema4B and Sema4D in organizing the postsynaptic specialization of synapses. First, we are utilizing immunocytochemistry techniques in cultured hippocampal neurons in which Sema4B or Sema4D gene expression has been decreased in order to determine precisely which aspects of glutamatergic and GABAergic postsynaptic specializations are disrupted. Secondly, we are performing structure/function studies to uncover the signal transduction pathways that mediate Sema4B and Sema4D-dependent glutamatergic and/or GABAergic synapse formation.


37.6/H3. Differential routing of VAChT and VMAT/NPY to separate projections of rat neonatal sympathetic neurons co-cultures with myocytes
A. VEGA1,2, S. J. BIRREN2, *M. A. MORALES1;
1Dept Cell Biol & Physiol, Inst. Invest Biomedicas UNAM, Mexico, Mexico; 2Biol., Brandeis Univ., Waltham, MA
Sympathetic ganglionic neurons express the vesicular monoamine transporter (VMAT) in vivo, as well as co-transmitters such as neuropeptide Y (NPY). When co-cultured with cardiac myocyte targets these neonatal neurons maintain their adrenergic phenotype. Although treatment with BDNF promotes cholinergic co-transmission that can be observed as an activity-dependent decrease in the beat rate of connected myocytes, these neurons show very low expression of the cholinergic marker vesicular acetylcholine transporter (VAChT). On the other hand, VAChT expression is induced either by treatment with CNTF, or by culturing the neurons for a three week period, although neither treatment induces the cholinergic transmission between neurons and myocytes. This raises the question of whether the two classical transmitters that are synthesized following CNTF treatment or long culture periods are routed to the same projections, or segregated to different neuronal process; and whether the heterogeneous cellular distribution of VMAT- and VAChT-containing varicosities can account for the lack of cholinergic release onto myocytes. We therefore explored the localization of VAChT, VMAT and NPY in all varicosities of rat neonatal sympathetic neurons co-cultured with myocytes for three days under control or CNTF conditions or after 3 weeks of culture. The neurons showed two types of VMAT/NPY-containing varicosities after 3 days in control culture: i) scarce, large (1.5-3.0 µ) and proximal to clusters of neuronal cell bodies and ii) small (≤1.5 µ) abundant and neurite-associated. CNTF induced weak VAChT expression in the type I varicosities but only in a subset of type II varicosities that were in regions with high neurite density. Three weeks of culture induced an abundant expression of VAChT in type I and II varicosities, but also in a new population of large varicosities proximal to cell bodies, that do not co-express VMAT or NPY. These data suggest that cultured sympathetic neurons differentially route VAChT and VMAT/NPY to separate neuronal projections. This could explain why VAChT expressing CNTF-treated neurons do not show cholinergic transmission onto cardiac myocyte targets. It also suggests preferential release of acetylcholine from VAChT-containing varicosities onto neurons, rather than myocytes in 3 weeks cultures, possibly potentiating adrenergic function.
MAM spent a sabbatical year at Brandeis University supported by DGAPA, UNAM, Mexico


54.4/Z29. A mechanism by which NMDA hypofunction, as may occur in schizophrenia, can produce thalamocortical dysrhythmia
*Y. C. ZHANG, J. LISMAN;
Biol, Brandeis Univ., Waltham, MA
The thalamus normally has slow oscillations (delta/theta) during sleep, but not during wakefulness. In schizophrenia among, other dysrhythmias, MEG recordings (Llinas; PNAS 96:15222, 1999) and human single cell electrophysiology (Jeanmonod et al Thalamus 1: 245-254, 2001) have provided evidence that, due to membrane hyperpolarization, thalamic neurons demonstrate T channel deinactivation, (Llinas and Jahnsen, Nature 297:406-407, 1982), which resulting in slow sustained rhythmic thalamocortical activity. A reduction in the function of the NMDA channels (NMDA hypofunction) has been strongly implicated in schizophrenia and we have therefore examined the effect of NMDA antagonist on inhibitory neurons of the nucleus reticularis. Previous work has shown that ambient glutamate is sufficient to activate NMDA channels, but in most cell types this effect is small because the channels are blocked by magnesium at resting potential. However, reticularis neurons contain NR2C channels, which have low magnesium block. We found that in these cells application of NMDAR antagonist (50µM APV) causes a larger hyperpolarization (7-8 mV) than in cortical pyramidal cells (1-2 mV). This hyperpolarization is sufficient to deinactivate T-channels; we find that whereas depolarization normally induces tonic firing in reticularis neurons, in neurons treated with APV, depolarization causes bursting of the kind generated by T-channels. Such abnormal bursting of reticularis neurons would be expected to produce bursting of the thalamocortical system. This prediction has been tested and confirmed (see SFN abstracts by Serulle et al and Yu et al). Taken together, these results suggest that NMDA hypofunction is a potential molecular mechanism of thalamocortical dysrhythmia.


64.6/GG34. Role of cholinergic activity in taste learning in p75 knockout mice
*D. NARAYANAN, S. NESELILER, D. KATZ, S. BIRREN;
Neurosci., Brandeis Univ., Waltham, MA
A number of studies have implicated the cholinergic system in the mediation of plasticity and in particular taste learning. We used a transgenic mouse model lacking the low-affinity neurotrophin receptor p75, a mutation known to increase the number of basal forebrain cholinergic neurons, to further examine the role cholinergic activity plays in taste learning. In conditioned taste aversion (CTA), we found what appears to be an intrinsic difference in learning between the mutant and wild-type mice- learning in the p75 mice extinguished more slowly than that of wild-types. Immunohistochemical analysis using an antibody against choline acetyltranferase (ChAT) revealed a significant increase in cholinergic innervations in the gustatory cortex of knockout mice in comparison with their wild type counterparts. Together, our results show a strong correlation between increased cholinergic innervation of the gustatory cortex and taste learning.


64.8/HH2. Distributed processing of taste concentration
*B. F. SADACCA1, D. B. KATZ2;
1Biol., 2Psychology, Brandeis Univ., Waltham, MA
To regulate fluid and solute intake, animals must properly identify the chemical identity of solutions, the concentration of solutes in those solutions, and the solutions’ value relative to physiological needs. These are particularly significant issues for sodium taste, some concentrations of which are avidly accepted while others are swiftly rejected. Forebrain taste regions including primary gustatory cortex (GC), the central nucleus of the amygdala (CeA) and orbitofrontal cortex (OFC) are essential for the proper valuation of different concentration sodium solutions. To examine the nature of this processing, I presented awake, freely moving rats with intraoral infusions of a taste array while recording isolated single-unit responses simultaneously in GC, CeA, and OFC. The array consisted of six tastes and a water rinse separating each taste delivery. I administered four concentrations of NaCl, including reliably palatable (0.15M), relatively neutral (0.01M; 0.3M) and reliably unpalatable (1.0M) concentrations. I also delivered highly palatable sucrose (0.1 M) and bitter, unpalatable quinine (0.001M). Here, I show that evoked taste responses within each region robustly track taste quality and taste palatability. Concentration specific processing proves to be less robustly dissociable.


64.16/HH10. Noise, oscillations and state sequences in a simple model of cortical sensory processing
*J. LV1, D. KATZ2, P. MILLER3;
1Dept. of Physics, 2Dept. of Psychology, 3Biol. and Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA
Recent data suggest that cortical neuronal activity processes through stimulus-specific sequences of states, with strong trial-to-trial variability in the timing of transitions between those states [1]. In this work we adapt a simple model [2] with rich dynamical behavior that has been shown to progress through chaotic state sequences. Our adaptation includes addition of cross-excitation between cells and varying noise in the circuitry within levels appropriate for cortical activity. We find that noise can convert the chaotic sequences into more regular oscillations. We find that upon adding an input (stimulus-dependent) current, the network with noise can switch to a different mode of oscillation, with reduction in oscillatory amplitude and a shift in frequency (see Figure). Such behavior is similar to the cortical response during periods of inattention when 10-12hz rhythms dominate in the absence of stimulus. We show how differences in noise level in the network can reflect differences in attentiveness in vivo. We investigate how changes in network connectivity that could arise through conditioning can alter the stimulus response and describe how such an altered network response differs from that produced by a change in stimulus. Our results are primarily based on firing-rate models and include an analytic treatment of the relative stability of different oscillating modes to parameter modifications. We also implement versions of the network with spiking neurons to ensure that Hidden Markov analysis of model spike trains yields the same variability of state sequences as seen in vivo [1].
[1] Jones et al. PNAS 104:18772 (2007)
[2] Afraimovich et al. Chaos 14:1123 (2004)
Figure: Firing rate of six different cell groups as a function of time. Stimulus arrives at t=5s.


64.17/HH11. Neural activity during a taste discrimination task in rat gustatory cortex
*T. YOSHIDA1, D. B. KATZ1,2;
1Dept Psychol, 2Volen Natl. Ctr. for Complex Systems, Brandeis Univ., Waltham, MA
Neural activities are modulated not only by the features of stimuli but also by the context in which animals receive the stimuli. It is known that taste stimuli evoke prolonged activity in the gustatory cortex (GC) when animals are allowed to taste freely, or when tastants are passively delivered to anaesthetized animals, while transient responses are observed when the animal is licking. To further address the context-specific modulation of taste response, here we examined neural activity in rat GC during a taste discrimination task in which rats have to discriminate taste type and make a quick behavioral choice. Specifically, we trained rats on a two alternative choice paradigm. A taste solution delivered via intra-oral cannula after the rat entered a center nose poke was associated with one of two locations (right or left nose poke); the rats were rewarded for correct response with water. We recorded single unit activities from GC in well trained animals during the task. Many neurons showed event-related activity during delay periods proceeding of taste/reward presentation and during the periods after taste/reward delivery. Some neurons respond to both taste and reward in similar way, which may be reflecting somatosensory input on the tongue, while others produced taste specific responses. Notably, we frequently observed quick and transient activities with a peak of around 200 ms in many taste/reward responsive neurons, suggesting that GC activity can be adapted to the task that animals are engaged.


91.8/SS71. Specificity versus associativity in associative based learning
*M. BOURJAILY, P. MILLER;
Brandeis Univ, Volen CCS, Waltham, MA
Many cognitive tasks require association of two stimuli to produce a response that differs from the response to either stimulus alone. For example, in the first phase of an associative transitive inference task, rats are presented with containers identifiable by a single cue odor (A or X) then a choice of two containers with odors (B or Y). To obtain reward, rats must learn that A predicts B and X predicts Y. Thus neurons responsive to specific associations (eg A then B) must arise.
In this study we investigate the requirements on network structure and plasticity rules for the formation of such an associative response to A then B that differs from X then B or A then Y. We begin with an initially randomly connected network of spiking neurons with/without structured inputs, using a similar task [negative patterning] without memory. We find that spike-timing dependent plasticity (STDP) tends to “over-associate” so cells responding to a combination of inputs (A and B) become responsive to A alone after many trials. Long-term potentiation of inhibition (LTPi) solves this problem (see Figure), by generating cross-inhibition that is essential to produce and maintain specificity in the circuitry. In further work, we use STDP with LTPi to generate stimulus-selective pools with persistent activity. This allows stimulus A to remain active throughout the delay until it is co-active with stimulus B. In all cases homeostasis is necessary to maintain a stable firing rate (we use multiplicative synaptic scaling). We discuss how these different plasticity mechanisms can be distinguished in the development of neural activity patterns during training in vivo.
Figure: Final pooled connectivity and example voltage traces following unsupervised learning via STDP and LTPi in a random network with the inputs shown.


162.10/GG1. Olfactory learning requires the taste system
*Y. FORTIS-SANTIAGO1, B. RODWIN1, D. B. KATZ2;
1Dept. of Biol., 2Psychology Dept., Brandeis Univ., Waltham, MA
It has long been known that the olfactory system directly affects taste system function_food is bland and tastes are difficult to identify when you have a cold. Here, we reveal this interaction between taste and smell to be reciprocal, showing that olfactory information is poorly processed when the central taste system is compromised. First, we demonstrated that socially transmitted food preferences (STFP) are learned based on a purely odor-odor association (between the breath of the “demonstrator” and the smell of the demonstrated food carried on the demonstrator’s breath). When rats’ olfactory receptor cilia were temporarily ablated via intra-nasal infusions of mild detergent before acquisition or testing, the normally conditioned preference for the food smelled on a conspecific’s breath was impaired. These impairments persisted a week later, confirming that the olfactory input is necessary for acquisition. We then performed a parallel set of experiments in which we inactivated gustatory cortex (GC) before acquisition or testing sessions. This manipulation also caused profound learning and retrieval impairments. Our data therefore suggest that central taste pathways are necessary to process olfactory input during the acquisition and expression of STFP, a finding that accords well with data demonstrating olfactory responses in GC neurons.


218.11. Making up for lost sound: Hearing acuity modulates neural recruitment for speech comprehension in older adults
*J. PEELLE1, V. TROIANI1, A. WINGFIELD2, M. GROSSMAN1;
1Dept. of Neurol., Univ. of Pennsylvania, Philadelphia, PA; 2Volen Natl. Ctr. for Complex Systems, Brandeis Univ., Waltham, MA
Declines in hearing acuity are ubiquitous in healthy older adults, but the effects of these changes on higher level cognitive abilities are unclear. Speech comprehension requires the rapid decoding of a complex acoustic signal and several levels of linguistic analysis, all while new information continues to arrive, and thus may be particularly vulnerable to decreases in the quality of perceptual information. In the current study we assess whether age-associated declines in peripheral hearing acuity influence higher-level processing of spoken language. We presented 16 healthy older adults (aged 60-77 years) with a series of short spoken sentences and monitored neural activity using BOLD fMRI. Hearing acuity was measured using standard pure tone audiometry between 250-6000 Hz for both ears, measuring the softest level at which subjects could reliably detect a brief tone. Pure tone averages (for 1kHz, 2kHz, and 4kHz) in subject's better ears ranged from 10-33 db HL, covering a range of normal hearing to mild hearing loss. Subjects' accuracy on the sentence comprehension task did not differ from young adults. To investigate the influence of hearing acuity on auditory sentence processing, we conducted a correlation analysis. For each subject we used the linear contrast of parameter estimates to summarize neural activity in each voxel for the sentence comprehension task, which we regressed against each subject's pure tone average in their better ear. This analysis showed less activity in bilateral superior temporal gyri in listeners with poorer hearing acuity, but increased activation in middle frontal gyri and premotor regions. We hypothesize that decreased acoustic signal results in less temporal activation, and that frontal regions are required to compensate with increased executive resources. These results indicate that decreases in sensory acuity found in healthy aging exert significant influence at the level of neural processing.


220.3. New mathematical model of the drosophila circadian clock explains the paradoxical effects of clockwork orange mutation
*H. M. FATHALLAH-SHAYKH1,2, J. BONA2, M. ROSBASH3, S. KADENER3;
1Dept Neurol Sci., Rush Univ. Med. Ctr., Chicago, IL; 2Mathematics, Univ. of Illinois at Chicago, Chicago, IL; 3Biol., Brandeis Univ., Waltham, MA
In the Drosophila circadian clock, cwo negatively regulates the transcription of per, tim, vri, pdpd1 as well as its own transcription. As compared to wild type, cwo-mutant flies exhibit lower amplitudes of per, tim, pdp1, and vri and higher levels of cwo mRNAs. We introduce a new system of ordinary differential equations to model the dynamical behavior of molecular networks and apply it to the Drosophila circadian clock. The goal is to find a justification for the paradoxical levels of mRNAs measured in cwo-mutant flies. Simulations generate 24-hour rhythmic oscillations that replicate biological data and show entrainment in response to time shifts (i.e resetting the clock in response to time-zone changes). Furthermore, in silico mutations replicate the behavior of the circadian clock in cwo-mutant flies. In silico targeted deletions of the inhibitory effects of the CWO protein reveal that vri appears to mediate the low amplitudes of per, tim, vri, and pdp1 in cwo-mutants. On the other hand, the high level of cwo mRNA in cwo-mutant flies is mediated by the CWO protein repressing its own transcript. The model is also consistent with our previous findings that the cwo promoter has a differentially high sensitivity to negative regulation by CWO protein.


237.18/D43. Neurophysiological mechanisms underlying thermal acclimation in a neuron of the vertebrate central nervous system
*T. M. SZABO1, T. BROOKINGS1, D. S. FABER2, T. PREUSS2;
1Biol Dept, Brandeis Univ., Waltham, MA; 2Domick P Purpura Dept of Neurosci., Albert Einstein Col. of Med., New York, NY
An animal's ability to adapt and behave normally in the natural environment is crucial to its survival, and one important factor it must adjust to is temperature. To study the effect of temperature acclimation on intrinsic membrane properties and the integrated functioning of a neuron in the vertebrate central nervous system we used the Mauthner (M-) cell as a model. The M-cell can be studied both physiologically in the intact brain as well as in a behaving animal, since it triggers a startle response when it fires. Animals acclimated for at least one month to 5°, 15° or 25°C had escape kinetics consistent with the general effects of temperature: slower in cold, faster in warm. Probability of escape increased and directionality decreased at 25°C, results that were also seen when acclimated animals were tested at 15°C. To examine the neurophysiology underlying these behavioral changes, we recorded from the M-cell intracellularly in animals acclimated under the same conditions. Some cellular properties were directly impacted by temperature including input resistance and action potential kinetics, although not to the extent seen in acute temperature exposure (Preuss and Faber, 2003). No differences were seen in length constant or threshold between the three populations. At VIIIth nerve-M-cell mixed synapses there was a reduction in the slope of the input-output relationship over many stimulation strengths at both 5° and 25° compared to 15°C. Kinetic differences in the coupling potential, which reflects presynaptic (VIIIth nerve) action potential kinetics, were consistent with general temperature effects, while tau of the chemical PSP was lower at both 5° and 25°C. An examination of feedback inhibition demonstrated a significant increase in cold-acclimated animals and decrease in warm-acclimated animals, results that are consistent with an increased probability of escape in warm-acclimated animals. Together, these studies demonstrate that while various aspects of the M-cell circuit are directly impacted by temperature effects in a predictable manner even after a period of acclimation, the opposing mechanistic actions of various systems, for example inhibition vs. input resistance, act to help the cell and animal maintain stable levels of activity. In addition, it seems likely that any disturbance of the excitatory/inhibitory balance produces computational problems for directional escape.


240.18/E40. Cell-type specific maintenance of neocortical firing type by network activity
*M. N. MILLER, S. B. NELSON;
Biol., Brandeis Univ., Waltham, MA
The adult neocortical microcircuit is composed of multiple discrete cell-types that differ morphologically, physiologically, and transcriptionally, and these cell-type-specific properties permit distinct functional roles within the network. Maturation and maintenance of cell-type specificity is most likely regulated by a complex interaction between genetic and environmental factors, but the relative contributions of these have not been directly examined. We combined genetic and anatomical labeling of cortical cell-types with chronic local muscimol delivery in adult mice in vivo to ask whether cortical network activity is necessary for the maintenance of cell-type specificity. 48 hours of local network inactivation increased the excitability of fast-spiking interneurons (FS) and reduced the excitability of intratelencephalic corticostriatal pyramidal cells (IT), but had no effect on their respective characteristic firing types. In contrast, pyramidal-tract projecting pyramidal cells (PT), which under control conditions exhibit spike-frequency acceleration in response to current injection, either lost acceleration to become non-adapting or, in the majority of cases, exhibited spike-frequency adaptation accompanied by a dramatic increase in input resistance. The combination of spike-frequency adaptation and high input resistance is reminiscent of both IT pyramidal cells and immature PT pyramidal cells, suggesting that PT physiological properties quickly regress to an immature and less-differentiated state if not actively maintained by network activity. Furthermore, the effect of chronic activity blockade on PT but not IT or FS populations indicates that activity-dependent maintenance of neuronal phenotype is cell-type specific.


240.22/F4. Monocular deprivation reduces the intrinsic excitability of layer 4 pyramidal neurons in binocular cortex
*M. E. LAMBO1, A. MAFFEI2, G. G. TURRIGIANO1;
1Biol., Brandeis Univ., Waltham, MA; 2Dept. of Neurobio. and Behavior, SUNY Stony Brook, Stony Brook, NY
Visual deprivation induces profound changes in visual response properties, but the activity-dependent plasticity mechanisms underlying them are poorly understood. Monocular deprivation (MD) rapidly decreases responsiveness of the deprived eye to visual drive. Here we examine the changes in intrinsic and synaptic response properties in the binocular region of primary visual cortex following 2 days of MD. We sutured one eye at p18 for 2 days and used whole-cell and perforated patch clamp recordings of layer 4 pyramidal neurons. Recordings were obtained from hemispheres contralateral and ipsilateral to the deprived eye and in sham operated rats, with the majority of comparisons being made between contralateral and sham conditions. Recordings of spontaneous firing rates under conditions that preserved synaptic drive indicated that MD reduced spontaneous firing by a factor of three (sham: 0.15±0.04 Hz, n=34; contra: 0.05±0.02 Hz; n=23; p<0.05). These results show that MD decreases layer 4 excitability; a change that could be due to decreased excitatory or increased inhibitory synaptic strength, or decreased intrinsic excitability. To test changes in excitatory synaptic strength, miniature excitatory postsynaptic currents (mEPSCs) and paired recordings from pyramidal neurons were performed. MD did not affect mEPSC amplitude (sham: 12.15±0.36 pA, n=21; contra: 12.57±0.62 pA; n=21; p=0.56) or the strength of recurrent EPSCs (sham: 10.66±1.20 pA, n=7; contra: 14.00±2.32 pA; n=19; p=0.21). To examine intrinsic response properties FI curves were generated with depolarizing current injections at a range of intensities, with synaptic currents blocked. MD induced a significant reduction in excitability (number of spikes/second) at all current injections above 0.04 pA (sham n=14; contra n=14; p<0.043) and a reduction in input resistance (sham: 292.7±16.9 MΩ, n=14; contra: 188.5±23.2 MΩ, n=14; p<0.002). To assess whether this reduction in excitability requires an imbalance in drive from the two eyes, we generated FI curves from rats that underwent 2 days of binocular lid suture (BD). BD did not induce a reduction in excitability (sham n=14; BD n=16; p>0.22 for all current injections). Overall, the data indicate that MD suppresses spontaneous activity, at least in part through a reduction in intrinsic excitability. Further, the reduction in intrinsic excitability can be partially explained by a decrease in input resistance (but likely also involves voltage gated channels), and is a process which requires competitive input from both eyes. One locus of activity dependent plasticity in visual cortex is thus the intrinsic excitability of cortical pyramidal neurons.


240.23/F5. Metaplasticity of intrinsic excitability of cortical layer 5 pyramidal neurons induced by visual deprivation
*K. NATARAJ, G. TURRIGIANO;
Dept Biol, Brandeis Univ., Waltham, MA
Changes in visual experience dramatically alter the organization of visual cortical circuits, but the cellular plasticity mechanisms that drive these changes are poorly understood. Here we examined the role of long term potentiation of intrinsic excitability (LTP-IE) of layer-5 pyramidal neurons in the experience-dependent changes induced by monocular deprivation (MD). MD was achieved with eyelid suture for 48 hours, starting at P18, and whole-cell patch clamp recording were obtained from the monocular region of primary visual cortex (Vm1) from the deprived and control hemispheres. Neurons from the deprived hemisphere had lower spontaneous firing rates than control neurons, and exhibited a right-ward shift in their firing rate vs. current (FI) curves, indicating a reduction in intrinsic excitability. LTP-IE was induced in control and deprived neurons by making the neurons fire 15 spikes at 40 Hz every 4 seconds for 10 minutes, in the presence of synaptic blockers (50µM APV, 20 µM DNQX, and 20 µM Picrotoxin). The induction protocol caused a significant increase in intrinsic excitability in cells from both hemispheres. However, MD induced a far greater increase in the LTP-IE in the deprived hemisphere compared to the control hemisphere (control hemisphere: 142.72±2.14% of control, n = 7; deprived hemisphere: 200.21±24.13% of control, n = 10: p < 0.001). Further, LTP-IE caused a leftward shift of the FI curve, and reduced the current threshold in both hemispheres, but did not alter passive neuronal properties, suggesting the involvement of voltage dependent conductances. These data suggest that MD reduces the intrinsic excitability of L5 pyramidal neurons by reducing LTP-IE. Further, the increased magnitude of LTP-IE in deprived cortex suggests that LTP-IE could play a role in recovery from an insult or visual deprivation


204.5. Dynamics of Taste Responses
D. Katz;
Dept of Psychology, Brandeis Univ, Waltham, MA.
Jones L. M., Fontanini A., Sadacca B. F., Miller P., Katz, D. B. (2007). Natural stimuli evoke dynamic sequences of states in cortical ensembles. Proceedings of the National Academy of Sciences, 104, 18772-18777.


367.9/JJ9. A method for parametric evaluation of angular path integration and dynamic spatial orientation
*P. A. DIZIO1,2, J. VENTURA1, J. KAPLAN1, I. SCHLEIFER1, M. LEHMANN1,3, J. R. LACKNER1,2;
1Ashton Graybiel Spatial Orientation Lab., 2Volen Ctr. for Complex Systems, 3Dept of Psychology, Brandeis Univ., Waltham, MA
Blindfolded subjects attempting to point continuously at the subjective vertical with an indicator stick while being rotated about their recumbent yaw axis accurately counterrotate the stick in 1g but keep it aligned with their body midline in a 0g force background. The failure to rotate the stick in 0g could be due to absence of integration of semi-circular canal angular velocity signals, an unchanging subjective vertical produced by symmetrical otolith and somatic pressure cues, or a combination of the two. We have developed a method for indicating angular self-displacement which is independent of subjective vertical and have used it to evaluate angular self-displacement as a function of physical self-displacement in 1g.
Nine subjects were tested in a servo-motor controlled tilting bed and in an upright rotating chair. They were blindfolded, wore earplugs, and received masking noise through noise-cancelling earphones. The bed and chair produced brief, naturalistic turns which followed raised cosine velocity profiles, .8-4 sec duration, 30-90°/s peak velocity, 7.5-75° displacement. Immediately after each turn, subjects rotated a joystick mounted on an axis parallel to the bed or chair axis to replicate the perceived amplitude of the turn they had just undergone. During tilts in the bed, all subjects overestimated the amplitude of the smallest turns, showed an increased overestimation as turn amplitude increased to about 20°, and a progressive reduction in overestimation as turn amplitude increased further. The largest turns were either over- or underestimated by different subjects. The same general pattern of errors was present during rotations about a vertical axis in the chair, but all subjects in the chair made a larger range of errors than in the bed, and 7/9 subjects showed a stronger tendency to overestimate turn amplitude in the chair than for comparable stimuli in the bed. The results indicate that integrated semi-circular canal signals contribute to apparent angular self-displacement estimates during both vertical and horizontal axis rotations, and otolith and somatosensory tilt cues contribute during horizontal axis tilts. Our new technique of haptic replication enables resolution of whether force background affects angular path integration.


379.14/QQ50. Arm inertia matrix measured using impulse response
*D. PIOVESAN1, A. PIEROBON1, P. DIZIO1,2, J. R. LACKNER1,2;
1Ashton Graybiel Lab., 2Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA
The estimation of limb segment inertia is crucial for calculating joint torques and stiffness. Using a technique based on impulse response, this study measured the inertial properties of the human upper limb during forward reaching movements. Thirteen subjects (10 males, 3 females; ages 32±14 years), participated in the experiment performing a set of 180 horizontal movements along the sagittal plane. Sixty percent of the movements were perturbed with a force pulse produced by a Phantom robot, at 1/4, 1/2 and 3/4 of the full hand displacement, for a duration of either 20 or 50 ms. Force magnitude (3, 4, and 5 N) and direction in the horizontal plane (45º, 165º and 285º, with 0º in the lateral direction) were randomly chosen for each perturbed trial. A load cell between the robot and a rigid wrist cuff measured the force pulse, and hand trajectory perturbation was measured with a set of three single axis accelerometers positioned on the cuff to form a right handed frame. The attitudes of the hand and arm segments were monitored using an OPTOTRAK.
We used the theorem of conservation of momentum to estimate the inertial matrix of the hand in the Cartesian space. The matrix of inertia in joint space was then estimated using the Jacobean matrix calculated in the position where the impulse was applied. Representing the Cartesian space hand-inertia matrices as ellipses, the minor principal axis was partially clockwise rotated with respect to the direction of movement. Our method was compared to seven methods which employ regression equations to predict inertias from critical limb dimensions. There was substantial agreement across methods in the orientation, magnitude, and shape of the inertia ellipses. The impulse response technique provides a direct estimate of the inertia of a planar two degrees of freedom linkage, without assuming the distribution and local value of density, and it can easily be implemented in common types of reaching experiments.


379.24/QQ60. Development of context-specific motor adaptation of object and limb dynamics in young children
*A. M. TORRES1,2, P. DIZIO1,2, J. R. LACKNER1,2;
1Ashton Graybiel Lab., 2Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA
Adults who adapt to a dynamic force field produced by a robotic manipulandum later show aftereffects when manipulating the deactivated robot but move accurately with their free arm, indicating that self-calibration of limb dynamics and learning of robot dynamics can be acquired and recruited separately. We have performed a cross-sectional study of context-specific self/object adaptation in 43 children 3 to 14 years old (27 male, 16 female). They made reaching movements while grasping a handle attached to a Phantom haptic interface device, which could apply a velocity-dependent force orthogonal to movement direction, 4 N/m/s. Reaches were directed horizontally along body midline, between landmarks 20 cm apart. The apparatus and environment were continuously visible. All subjects learned within 32 movements to compensate for the lateral deviations initially caused by the force field. After adapting, each child made a single reach either grasping the deactivated robot or with his/her free hand, followed by 8 reaches with the robotic force field on, and finally a single reach in the free or grasping null field conditions. The order of the free and grasping null field movements was balanced within each age group. When the force was inactivated and adapted subjects continued to grasp the handle, all ages showed an aftereffect that mirrored the original error caused by the force field. When subjects released the handle and reached freely, the youngest subjects showed the same aftereffect as in the grasping condition but as age increased the aftereffect magnitude diminished and was absent by age 8. This shows that the ability to separately modify control of one’s own body and of external objects in a context-specific manner is a developmental achievement.
In a second experiment (n=21), the robot applied a supposedly familiar type of velocity-dependent force, anti-parallel to movement direction (damping), which initially retarded movement trajectories. After adaptation, reaches made while grasping the inactivated manipulandum showed negative aftereffects and free reaches showed no aftereffects, independent of age. This implicates a role of experience in the development of context-specific self/object motor adaptation.


417.8. A function for the large PDF cells in Drosophila Arousal
*Y. SHANG1, M. ROSBASH2;
1Dept Biol., Brandeis Univ., Waltham, MA; 2Dept Biol., Brandeis Univ/HHMI, Waltham, MA
Light regulates Drosophila activity as well as that of other diurnal animals, but the relevant arousal pathways within the adult fly brain remain largely unknown. Consistent with the notion that peptidergic neurons may be relevant to arousal , acute stimulation of a broad set of peptidergic neurons with the traditional Gal4-UAS/Gal80 system caused high levels of nighttime activity. The expression pattern of this Gal4 driver includes the 5 PDF-containing large ventral lateral neurons (l-LNvs) of the circadian system. These cells have recently been shown to be light-sensitive, but they have never been assigned a circadian or a behavioral function despite being among the first circadian neurons identified in flies. We first show that exciting the large LNvs is necessary for much of the early nighttime activity caused by abnormal firing of the broader peptidergic cell population at night. We then combined three expression systems: Gal4-UAS/Gal80, LexA-LexAop, and the FLP/FRT technique to develop a novel mosaic technique that achieves single or few neuron resolution, in this case specifically within the l-LNv population. The approach allowed us to alter the activity of a small subset of the l-LNvs and to simultaneously label only these cells. It showed that hyperexcited l-LNvs are sufficient to promote locomotor activity at night. We also showed that l-LNvs are necessary for light-induced phase shift. The data indicate that l-LNvs are the major sources of photic information not only for the diurnal activity mediated by the arousal-sleep circuit but also for the circadian clock.


422.12/B38. Physiological and transcriptional maturation of a subtype of cortical GABAergic interneuron
B. W. OKATY, M. N. MILLER, K. SUGINO, C. M. HEMPEL, *S. B. NELSON;
Dept Biol MS#008, Brandeis Univ., Waltham, MA
Cortical GABAergic interneurons can be segregated into distinct subtypes based on their electrophysiology, morphology, and gene expression. Recent evidence suggests that these subtypes arise from regionally distributed progenitors born at distinct times as a result of divergent transcriptional networks initiated in the embryo. However, a detailed description of their postnatal maturation is presently lacking. To this end, we screened mouse whole genome microarrays and performed whole-cell patch clamp recordings of genetically labeled parvalbumin positive fast-spiking (FS) basket cells over a range of time points from P7 to P40. Over the course of maturation, FS basket cells required more input to reach spike threshold, but developed the ability to fire repetitively over a wider range of inputs at progressively higher firing rates. Immature FS cells also displayed spike frequency adaptation, a feature that is subsequently lost by P10. The amplitude and frequency of excitatory postsynaptic currents was found to peak at p15 and then decrease, while a shift to faster decay kinetics for inhibitory postsynaptic currents was observed between p10 and p15. Consistent with these findings, the microarray screen revealed changes in the expression levels of several ion channel and receptor transcripts previously shown to contribute to the observed electrophysiological traits. Additionally, Gene Ontology (GO) overrepresentation analysis showed that genes related to ion channel activity, calcium binding, and cell growth were enriched among the set of developmentally regulated genes. Moreover, correspondence between phenotypic changes and the developmental trajectories of hundreds of differentially expressed transcripts suggests possible functions for previously uncharacterized genes.


447.5/Y5. Synaptic dysfunction in Rett syndrome: studies in a mouse model
*V. S. DANI, S. B. NELSON;
Biol. Dept., Brandeis Univ., Waltham, MA
Rett syndrome is a prevalent X-linked mental retardation disorder, which manifests itself postnatally, suggesting defects in postnatal maturation of neuronal circuits. Mecp2-null mice, an animal model of Rett Syndrome, recapitulate many features of the human disorder including deficits in learning and memory. Impaired plasticity mechanisms such as long-term potentiation (LTP) have also been observed at hippocampal and cortical excitatory synapses during symptomatic stages in these mice. Previously, we showed a decrease in spontaneous firing rates of Layer 5 cortical pyramidal neurons in slices from Mecp2-null mice, due to an imbalance between excitatory and inhibitory synaptic drives onto pyramidal neurons. In order to characterize the specific nature of the synaptic deficit, we performed quadruple whole cell recordings in acute cortical slices and studied the properties of monosynaptic connections between Layer 5 pyramidal neurons. The probability of finding connections was significantly reduced in Mecp2-null slices compared to Wild-type (WT) controls (Connection Probability::WT: 0.103; Mecp2-null: 0.041; P<0.05 Chi-squared Test). Among the connections found, we observed a decrease in the average EPSP amplitude in Mecp2 null mice. Using a spike timing dependent plasticity paradigm, induction of LTP was found to be equally effective in both Mecp2 null as well as WT slices from four week old animals. These results suggest that decreased excitation due to sparse connectivity between cortical excitatory neurons in Mecp2 null mice can be one of the primary deficit in local cortical microcircuits, preceding the impairments in learning and LTP found at advanced stages of the disorder.


459.1/FF2. Characterizing internal dynamic states and their emergence in the primary visual cortex of the awake ferret
*J. FISER1, M. CUI2, C. CHIU3, M. WELIKY4;
1Dept Psychol, Brandeis Univ., Waltham, MA; 2Psychology, Program in Cognitive Neurosci., Brandeis Universiy, MA; 3Neurosci., Albert Einstein Col. of Med., Bronx, NY; 4Brain and Cognitive Sci., Univ. of Rochester, Rochester, NY
According to recently emerging views on visual cortical processing, activity in the primary visual cortex is governed by dynamically changing internal states of the system modulated by the incoming information rather than being fully determined by the visual stimulus. We analyzed systematically the dynamical nature of these states and the conditions required for their emergence.
Multi-electrode recordings in the primary visual cortex of awake behaving ferrets (N=30) were analyzed after normal and visually deprived development at different ages spanning the range between postnatal day (P) 24 and P170. Visual deprivation has been achieved by bilateral lid suture up to the time of the visual tests. Multi-unit recordings were obtained in three different conditions: in the dark, while the animals watched random noise sequences, and while they saw a natural movie. 10-second segments of continuous recordings under these conditions were used to train two alternative state-dependent models, one based on Hidden Markov modeling that assumes internal dynamical dependencies among subsequent internal states and the other based on Independent Component Analysis which does not assume such dependencies. HMM significantly outperformed ICA (p<0.001) for both normal and lid sutured animals. In addition, HMM performance increased with age (p<0.001), more so than ICA did (p<0.001). We also assessed the similarity between different underlying states across different conditions (Movie, Noise and Dark), by computing the Kullback-Leibler distance between the probability distribution of the observed population activity generated by the underlying states. We found that, in general, similarity between underlying states across conditions strongly increased with age for normal animals, but this similarity remained significantly lower than that for lid sutured animals (p<0.0001). In addition, the number of transitions in the oldest age group was higher in normal animals compared to lid sutured ones (p<0.001).
The result suggests that positing dynamic underlying states that emerge with age and can capture the behavior of cell assemblies is critical in characterizing the neural activity in the primary visual cortex. However, both the behavior and the emergence of these states depend only partially on proper visual input, and it is determined to a large extent by internal processes.


459.12/FF13. The relationship between awake and anesthetized neural responses in the primary visual cortex of the rat
*B. L. WHITE, J. FISER;
Brandeis Univ., Waltham, MA
Much of what we know about visual processing in the brain is based on neural data collected in anesthetized animals assuming that the essential aspects of the computations are preserved under such conditions. However, recent findings support an alternative view that visual processing depends upon ongoing activity, which is significantly altered in anesthetized preparations. Therefore, it is critical to assess how well the characteristics of neural responses to various stimuli in the anesthetized animal can predict responses in the awake animal.
We collected multi-electrode recordings from the primary visual cortex of adult rats under different levels of anesthesia and while awake. Anesthesia was maintained by isoflourane concentrations between 0.6% to 2.0%, ranging from very lightly anesthetized to deeply anesthetized. Isolated unit and local field potential (LFP) activity were collected from sixteen electrodes. Responses were compared between conditions of darkness (the spontaneous condition), a natural scene movie, and full-field white-black modulation at frequencies of 1Hz, 2Hz, 4Hz, and 8Hz. There were significant, up to two-fold modulations of measurements of average firing rates, bursting rates, power spectral densities, population sparseness, and coherence between stimulus conditions in awake and anesthetized animals. However, there were strong interactions between the particular stimuli used and the condition of the animal, and due to these interactions responses in the awake condition could not be well predicted by the anesthetized responses. While, in general, coherence decreased with lower concentrations of isoflurane as suggested by previous findings, coherence in the theta band actually peaked at 4 Hz visual stimulus modulation while awake, and that coherence in the gamma and alpha bands reached a minimum at 1-2Hz stimulation while under anesthesia. We suggest that anesthesia selectively modulates the neural dynamics in the cortex, and thus the patterns of visually-evoked responses in the awake and anesthetized animal are not related to each other in a straightforward manner.


Sleep: Studying a Human Behavior in an Insect
L. C. GRIFFITH;
Dept Biol MS008, Brandeis Univ., Waltham, MA
Every day our brains cycle between waking and sleeping states. Both of these brain states are highly active, but the nature of the activity and the connection of the brain to the outside world in each state are distinct. How the brain switches between these two modes of operation has been studied for many years in mammalian model systems and we are just beginning to understand the very complex structure of the switch that controls sleep. How multiple external and internal events, such as sensory input, sleep deprivation and the circadian clock, which can operate on very different time scales, are integrated is not understood.
In recent years, work from my lab and others has exploited the new genetic and electrophysiological tools available in Drosophila to push forward our understanding of sleep by identification and manipulation of the underlying circuitry. In this talk I will discuss the evolutionary conservation of sleep at the behavioral and circuit levels in the fly and how dissection of the circuitry in this organism may allow us to understand the fundamental nature of sleep regulation.
As in mammals, sleep in flies is regulated by both circadian and homeostatic drives, and the onset of the sleep state correlates with changes in high frequency brain activity and an increase in arousal thresholds for acute sensory stimuli. The circuit that generates this behavior consists of GABAergic sleep-promoting neurons which make contacts with wake promoting neurons that are also part of the circadian clock circuit and receive light input. Other brain areas have been identified that may act to modulate this small core circuit. The ability to acutely and chronically control neuronal activity in specific parts of this circuit will allow a detailed understanding of the fly sleep switch. Pressing questions such as how integration over multiple time scales can occur in the switch can be addressed using these tools and will have implications for studies of mammalian switch function. Identification of new circuit components that feed into the integrator, and the ongoing efforts in gene discovery which are providing new molecules that regulate sleep, will make flies true contributors to our understanding of this human behavior.


525.8/B21. GFP-CaMKII dynamics and phosphorylation in synaptic remodeling
*C. E. TAFT, G. G. TURRIGIANO;
Biol., Brandeis Univ., Waltham, MA
In addition to strengthening existing synapses, CaMKII has been suggested to play a role in the activity-dependent formation of new synaptic connections (Pratt et al., 2003). Transfection of neurons with activated CaMKII selectively increases the rate at which new contacts are formed without affecting the rates of synapse loss or stabilization (Pratt, Taft et al., 2008). Here we compared the dynamics of GFP-CaMKII and changes in its activation state at synaptic sites to the fate of particular synaptic connections.
We performed time-lapse imaging on pairs of cultured rat visual cortical neurons, transfected 16-20 hours prior with GFP-CaMKII (postsynaptic) and mCherry (presynaptic; a soluble marker that allowed us to visualize axons). We tracked formation and loss of contacts between pre and postsynaptic partners over time, and the accumulation of CaMKII at these sites, by taking z-stacks (0.2um) every 20 minutes for 3 hours. We identified contacts that were gained, lost and those that remained stable throughout the experiment and used this information to obtain rates of gain and loss. After imaging, the cultures were fixed and double-labeled using antibodies against the presynaptic marker VGlut1 (a vesicular glutamate transporter) and phospho-T286 to detect constitutively active CaMKII.
Using both PSD-95-EGFP (a postsynaptic scaffolding protein) and GluR1-EGFP (an AMPA receptor subunit), we have shown that rates of gain and loss are equal. When we track axodendritic contacts that accumulate GFP-CaMKII, we also see equal rates of gain and loss. There is high colocalization (77%) of VGlut1 and GFP-CaMKII, suggesting that most of these puncta are localized to synaptic sites. We previously saw that the area of PSD-95 puncta was the same regardless of whether a contact was stable or labile. Interestingly, GFP-CaMKII puncta have a signicficantly higher area at stable synapses than at sites where puncta were recently gained (p=.006) or lost (p=.02), indicating that more CaMKII is present at stable synaptic sites. There is also significantly more phospho-T286 in puncta at newly formed contacts than at contacts that are stable (p=.02). These results suggest that high levels of constitutively active CaMKII are associated with the formation of new synaptic contacts. In contrast, stable contacts have more CaMKII than newly formed contacts but a lower proportion of CaMKII is in the active state. These data suggest that CaMKII signaling helps to drive the formation of new synaptic contacts.


529.16/C46. Developmental and activity dependent regulation of TrkB receptor isoforms
*B. K. BRACKEN, G. G. TURRIGIANO;
Biol., Brandeis Univ., Waltham, MA
BDNF and its primary receptor TrkB are important for cortical development. TrkB is expressed in several alternately spliced forms, but little is known about developmental expression of the isoforms, or how that expression changes in response to altered activity. Rodent primary visual cortex (V1) is an excellent experimental preparation as activity levels can be altered with visual deprivation protocols such as monocular deprivation (MD) and dark rearing (DR). We used real-time RT PCR to quantify changes in mRNA expression of all four forms of the TrkB receptor, full-length TrkB (TrkB.FL) and three truncated forms of the receptor (TrkB.T1, TrkB.T2, and TrkB.T4), during normal development and in response to MD and to DR. Many studies examine V1 as a whole, thus masking any input-related changes that may be occurring, so we divided V1 into monocular (mV1), which receives input from one eye, and binocular (bV1), which receives input from both eyes.
During overall development, the relative amount of TrkB.FL decreased in relation to the truncated forms of the receptor in both mV1 and bV1. TrkB.FL mRNA expression decreased (P<.01), while the expression of TrkB.T1 (P<.001) and TrkB.T4 (P<.05) increased throughout life. Expression changes due to MD were distinct from those seen in response to DR, but in both cases, TrkB.T4 was the major isoform regulated by activity. T4 expression decreased by 75% in mV1 and by 90% in bV1 due to MD, but DR induced much larger changes in receptor mRNA expression that were in the opposite direction. In mV1 DR resulted in a 6-fold increase in .T4, and in bV1 DR resulted in a 3-fold increase in .T2, a 5-fold increase in .T4, and a 3-fold increase in P75. In both cases, though, TrkB.T4 was the major isoform regulated by activity. Taken together, these data indicate that the expression of the truncated TrkB isoforms, not just TrkB.FL is important both in normal development and in response to changes in activity levels.


540.8/L2. Synaptic scaling requires the GluR2 subunit of the AMPA receptor
*M. A. GAINEY, J. R. HURVITZ-WOLFF, M. E. LAMBO, G. G. TURRIGIANO;
Biol., Brandeis Univ., Waltham, MA
Two functionally distinct forms of synaptic plasticity, Hebbian long-term potentiation (LTP) and homeostatic synaptic scaling, are thought to cooperate to promote information storage and circuit refinement. Both arise through changes in the synaptic accumulation of AMPA receptors (AMPAR), but whether they use similar or distinct receptor trafficking pathways is unknown. Cultured rat cortical neurons treated with TTX for 24 hours show enhanced AMPA miniature excitatory postsynaptic current (mESPC) amplitudes but no change in current rectification, suggesting scaling increases accumulation of GluR2-containing AMPARs. To determine the role of GluR2 in scaling, we knocked down the AMPAR GluR2 subunit with an RNAi hairpin in cultured rat cortical neurons for 24 to 48 hours and show that synaptic scaling relies upon the GluR2 subunit. The expression of LTP was not affected by GluR2 knockdown, indicating that synaptic scaling and LTP are both functionally and molecularly distinct. The mechananism by which GluR2 regulates scaling remains unknown, but two potential mechanisms depend on C-tail interactions. One hypothesis is that changes in the number of “slots” in scaffolding proteins allow for changes in the accumulation of AMPA receptors at the post-synaptic membrane during scaling. Another possibility is that changes in the accumulation of receptors at the synapse is due to an altered rate of insertion of GluR2-containing AMPA receptors into the post-synaptic membrane. We used GluR chimeric proteins to examine the role of the various AMPAR protein-interaction domains in regulating scaling. When neurons are co-transfected with the GluR2 RNAi hairpin and RNAi-insensitive GluR2, scaling is rescued, as shown by an increase in mESPC amplitude. Co-transfection of the GluR2 RNAi hairpin and an RNAi-insensitive GluR2 subunit with a GluR1 C-tail (GluR2/CT1) blocks the rescue in scaling, indicating that the GluR2 C-tail has a regulatory role in scaling. Moreover, the GluR2/CT1 protein localizes to the synaptic membrane, suggesting that the lack of scaling is not due to the subunit’s failure to traffic to the synaptic membrane but rather from a lack of GluR2 interactions with specific C-tail binding proteins, such as GRIP1/2, ABP, or PICK1. Ongoing experiments will identify the specific C-tail interactions with trafficking proteins that are critical for synaptic scaling.


540.15/L9. TNFalpha is required for the maintenance but not induction of Synaptic Scaling
*C. C. STEINMETZ1, G. G. TURRIGIANO2;
1Turrigiano Lab., 2Biol. Dept/Turrigiano Lab., Brandeis Univ., Waltham, MA
Synaptic scaling (SS) is a form of homeostatic plasticity that tends to restore neuronal activity to ‘baseline’ levels in response to altered activity (Turrigiano et al. 1998). It has recently been shown that SS is induced by cell-autonomous changes in postsynaptic spiking, is mediated by a drop in somatic calcium influx, and requires transcription (Ibata et al., 2008). Paradoxically, in hippocampal neurons it has been shown that a glial derived factor, TNFalpha (TNFa), mediates activity-dependant changes in synaptic activity (Stellwagen and Malenka, 2006). TTX treatment induces SS within 6 hrs, and the magnitude of SS is greater after 24 hrs. To determine whether TNFa is required for the initial induction of SS or involved in long-term maintenance of SS in cultured cortical pyramidal neurons, electrical activity was blocked by application of TTX with or without the soluble form of the TNFa Receptor (sRTNFa) for 6 and 24 hours and miniature excitatory postsynaptic currents (mEPSCs) were recorded after 7-9 DIV. We found that an acute application of TNFa mimicked TTX-induced SS and that coapplication of TTX and sTNFaR for 24h blocked SS. In contrast, coapplication for 6 hrs induced normal SS, suggesting that the early phases of SS do not rely on TNFa signaling. Moreover, we found that when SS was first induced by 20 hr of TTX, brief application (6 hr) of sRTNFa did not reverse it. In contrast, 20h sRTNFa application followed by 6h TTX application blocked SS. Taken together, this data suggested that TNFa is involved in long-term maintenance of synaptic properties necessary for the expression of SS rather than an instructive signal necessary for its initial induction. Currently, we are exploring the changes in both AMPA receptor subunits and synaptic scaffolds protein in the different conditions mentioned above. This in vitro study should significantly increase our understanding of the molecular mechanisms of activity-dependent refinement of neuronal connectivity.


574.14/OO13. Serotonin alters the intrinsic membrane properties of gastric mill neurons in the crab C. borealis
*R. GRASHOW, A.-E. TOBIN, E. MARDER;
Biol. Dept, Brandeis Univ., Waltham, MA
Neuromodulation enables networks of neurons to produce a variety of behaviors by altering synaptic and intrinsic membrane conductances. For example, serotonin (5-HT) changes the output of several circuits in the stomatogastric ganglion of crustaceans (Flamm and Harris-Warrick, 1986; Beltz et al. 1984). Understanding how serotonin changes the circuit output requires understanding its effects on the component neurons.
To examine serotonin’s effect on the gastric mill (GM) neuron, we pharmacologically isolated the GM neurons, and measured the following intrinsic properties: input resistance, resting membrane potential, threshold of the first spike and the spike frequency versus injected current (F-I) curve. We applied 10-6 M serotonin and re-measured the intrinsic properties.
We found serotonin hyperpolarizes the voltage threshold of the first spike, and depolarizes the resting membrane potential, thus increasing the excitability of the cells. When current ramps were applied the spike shapes during the ramps differed between control and serotonin application. During each current ramp the spike shape changed as the cells were depolarized suggesting that spike shape may depend on the voltage of spike onset or spike frequency. The difference between spike shapes in control and serotonin conditions may be a result of different membrane voltages, spike frequencies, and/or application of the neuromodulator. These results indicate that serotonin is acting on intrinsic membrane properties that affect the dynamics of spike initiation and contribute to the overall output of the network.


574.15/OO14. Temperature-dependent cholinergic modulation of a small neural network
*M. FISEK1, L. S. TANG2, E. MARDER2;
1Biol., 2Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA
Nervous systems must maintain proper function in the face of changing internal and environmental demands. In the wild, C. borealis experiences large temperature fluctuations ranging from 5 to 25oC. Presumably, the animal must be able to produce the proper rhythmic output that is necessary for feeding behavior across this temperature range. We have previously shown that one neural substrate for this behavior - the pyloric network of the stomatogastric nervous system - maintains robust network activity across this temperature range. Since neuromodulation of the pyloric network is crucial for the maintenance and versatility of network output, we investigated the extent to which cholinergic modulation reliably reconfigures the circuit in a range of physiologically relevant temperatures.
Previous studies regarding this question have shown that the cellular actions of neuromodulators can be temperature dependent. Here we report that the actions of the cholinergic agonist oxotremorine on the pyloric rhythm are temperature dependent at the level of the network output in three different conditions. 1) With the modulatory inputs to the STG intact, oxotremorine significantly increases the pyloric cycle frequency at high temperatures but not at low temperatures. 2) When the modulatory inputs are blocked, the pyloric network is silenced. In this condition, oxotremorine continues to elicit a robust rhythm at all temperatures tested (T = 7 to 31 oC). This oxotremorine-elicited rhythm displays a different temperature sensitivity compared to the rhythm produced under control conditions. 3) In the presence of the Na+ channel blocker tetrodotoxin (TTX), oxotremorine can still elicit a robust network activity. The oxotremorine-elicited rhythm in the presence of TTX also displays different temperature sensitivity.
These results suggest that the effects of cholinergic modulation of the pyloric rhythm are strongly temperature dependent and do not reconfigure the circuit in similar ways at different temperatures.
While it is not surprising that the temperature sensitivity of single networks can be altered by neuromodulation, it is interesting that oxotremorine can extend the operational temperature range of the pyloric network, whereby robust network activity is maintained at higher temperatures than without oxotremorine. Qualitatively, these results appear similar to the extension of network operating range induced by high-temperature acclimation and suggests a possible mechanism for acclimation-induced network plasticity.


634.18/E31. BDNF regulates neuron to neuron synaptic transmission in rat sympathetic neurons co-cultured with cardiac myocytes
*J. A. LUTHER, S. BIRREN;
Dept Biol, Brandeis Univ., Waltham, MA
The sympathetic nervous system is an important homeostatic regulator of cardiovascular functioning and blood pressure. Many therapeutic compounds used to treat heart disease and high blood pressure are directed toward sympathetic neurotransmission. A better understanding of mechanisms that control sympathetic function could lead to more effective treatments for these diseases. We find that when cultured with cardiac myocytes sympathetic neurons form functional cholinergic connections between each other as well, as functional noradrenergic connections onto myocytes. Previous work has shown that neurotrophins influence both the strength of synaptic transmission and identity of transmitters released at neuron-myocyte synapses in cultures containing the two cell types. While it is clear that the properties of synaptic contacts between sympathetic neurons and the heart have important consequences for cardiovascular physiology, it is less clear how cholinergic synaptic transmission between neurons in sympathetic ganglia influence the functioning of this system. Here we show that neurotrophins also regulate the neuron-neuron synaptic cholinergic transmission in neuron-myocyte co-cultures. Spontaneous network activity develops in neuron-myocyte co-cultures after 10-14 days. This activity is dependent on excitatory cholinergic transmission between neurons as evidenced by reversible blockade by 100 μM hexamethonium, a nicotinic cholinergic antagonist. Whole-cell patch-clamp recordings reveal that a 15 minute bath application of 100 ng/ml brain derived neurotrophic factor (BDNF) leads to a significant increase in frequency (52.4 ± 9.5 %) and amplitude (7.8 ± 5.4 %, n = 7) of spontaneous excitatory synaptic events. In contrast neither effect was seen in control experiments using saline alone (n = 4). Additionally, an increase in amplitude was also observed in evoked synaptic responses between a synaptically coupled pair of neurons (4.0 ± 0.1 mV vs. 4.9 ± 0.1 mV in control vs. BDNF, p < 0.05 Student’s t-test). This data suggests that neurotrophins, which are released from both sympathetic neurons and sympathetically innervated tissues, may play a role in regulation of the sympathetic system in vivo.


680.1/RR30. Striatal BOLD response and memory enhancement for cues predicting monetary wins and losses
B. C. WITTMANN1, G. TAN1, J. E. LISMAN2, R. J. DOLAN1, *E. DUZEL3;
1Wellcome Trust Ctr. for Neuroimaging, Univ. Col. London, London, United Kingdom; 2Brandeis Univ., Waltham, MA; 3Inst. Cognitive Neurosci., London, United Kingdom
Dopaminergic projections from the substantia nigra, ventral tegmental area [SN/VTA] to the hippocampus are considered to be critical for long-term plasticity in declarative memory. However, it is unclear to what extent this dopaminergic pathway is specifically activated and long-term memory is enhanced only by rewards as opposed to aversive stimuli, which can also elicit striatal activation. Here, we investigated the relationship between SN/VTA activation by monetary rewards (wins) and punishments (losses) and long-term memory formation in healthy volunteers. In a mixed block and event-related fMRI study, three blocks contained rewards and three blocks contained punishments. Within each block, two categories of pictures (indoor and outdoor) predicted the feedback state of each trial.Participants were either rewarded for correct responses in a reaction time task (in reward blocks), punished for incorrect responses (in punishment blocks), or neither (no wins or losses; this category constituted 50% of trials in each block). In the subsequent task, reaction times were significantly shorter for punished trials than for rewarded trials and for rewarded trials vs. neutral trials. Pictures that predicted reward were associated with stronger activity in medial prefrontal cortex (PFC), the SN/VTA and ventral striatum than pictures that predicted punishment. The reverse contrast revealed stronger activation of insula, amygdala and hippocampus. At the time of outcome, wins vs. losses were associated with stronger activity in medial PFC and ventral striatum. Compared to wins, losses elicited more activity in other striatal areas, SN/VTA and insula. Long-term memory for cue pictures as tested one day later showed that both recollection and familiarity rates were enhanced for pictures that were associated with reward or punishment prediction at encoding. These findings suggest that reward and punishment engage mesolimbic structures through different mechanisms and contribute to understanding motivational effects on episodic memory.


760.1/EE19. NMDA-receptor block induced low frequency oscillations in the thalamocortical circuit: An in vitro voltage sensitive dye imaging study
E. YU1, S. CHOI1, J. LISMAN2, *R. R. LLINAS1;
1Dept Physiol & Neurosci, New York Univ. Sch. Med., New York, NY; 2Dept Biol, Brandeis Univ., Waltham, MA
Thalamocortical recurrent connectivity has been shown to be a central mechanism in the generation of cognition in humans and other mammalian forms. In addition the possibility has been proposed that several psychiatric and neurological conditions may be related to abnormal resonant frequencies in this thalamocortical recurrence. Such pathological events have been addressed as a general condition described as Thalamocortical Dysrhythmia Syndrome (TDS). Indeed, in pathology such as found in Parkinson’s disease, tinnitus, central pain, OCD and schizophrenia, among others, a low frequency electrical activity is observed using EEG or MEG and single cell recordings at specific cortical and thalamic sites relating to the particular affliction. In this study, we used voltage-sensitive dye imaging in mouse thalamocortical slices, to investigate the effect of D-AP5, an NMDA receptor blocker. Indeed it has been reported that D-AP5 placed at the reticular thalamic nucleus can induce the schizophrenic like symptom in rodents. We thus investigated whether such pharmacological intervention could results in a thalamic oscillation required for TCD. Local addition of D-AP5 to mouse thalamocortical slices in vitro, in the region of reticular nucleus (RT), resulted in the induction of low frequency oscillation in the RT activity with a frequency close to 6Hz (theta band), similar to that seen in TCD patients. These result agreed with the reports which showed increased low frequency EEG activity in the schizophrenia patients and suggest the functional blocking of NMDA receptor in the thalamocortical circuit could be one of the pathophysiological mechanisms in the schizophrenic symptom. In a related set of studies it was demonstrated that D-AP5 results in the hyperpolarization of thalamic neurons and the activation of T type calcium channels resulting in neuronal low frequency oscillation. Similarly it was also shown that in such conditions GABAergic inhibitory potentials from the thalamic reticular nucleus serve as one of the pace makers for this Theta oscillation.


760.24/FF14. Increase of oscillatory inhibitory synaptic events in thalamic relay neurons after inhibition of NMDA-mediated transmission
*Y. SERULLE1, F. J. URBANO2, J. E. LISMAN3, R. R. LLINAS1;
1Physiol. and Neurosci., NYU Sch. of Med., New York, NY; 2Inst. de Fisiología y Biología Mol. y Neurociencias (IFIBYNE), Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina; 3Dept. of Biol. and Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA
Thalamocortical activity is the product of the intrinsic properties of thalamic neurons, their recurrent connectivity with the cortex and the synaptic input from sensory and mesencephalic neurons. Abnormal thalamocortical rhythms play an important role in the pathophysiology of different neuropsychiatric diseases, including Parkinson’s disease, schizophrenia, neurogenic pain and tinnitus. In fact, it has been established that compared to controls, patients suffering from the above-mentioned disorders exhibit an increase in low-frequency (theta) rhythmicity. Low-frequency oscillatory activity is sustained by the activity of T-type calcium channels, which are activated at membrane voltages negative to resting potentials. Recent work (see Zhang and Lisman, and Yu et al., this meeting) indicates that NMDA antagonists, which are known to reproduce many aspects of schizophrenia, can hyperpolarize cells of the nucleus reticularis and induce bursting. To study the consequences for thalamic relay cells, we obtained patch-clamp recordings from ventrobasal thalamic relay neurons in vitro. Application of APV in the thalamocortical slice induced a hyperpolarization of thalamic relay neurons. Voltage- and current-clamp experiments showed that application of APV and CNQX increased the frequency of both spontaneous inhibitory postsynaptic currents (IPSCs) and potentials (IPSPs) in ventrobasal neurons, most likely generated by thalamic reticular neurons burst firing. Moreover, the frequency at which these inhibitory events occur is in accordance with the frequency at which reticular thalamic neurons oscillate, suggesting that in the absence of cortical input, the intrinsic properties of thalamic reticular neurons may regulate the activity of thalamic relay neurons. Current clamp experiments further indicate that the oscillatory inhibitory input results in oscillatory thalamic burst activity. Such bursting may establish a recurrent thalamocortical dysrhythmia. Observation of this dysrhythmia in vitro opens the door for its biophysical analysis and the identification of pharmacological agents that can abolish it.


792.6/TT54. Loss of dCASK produces a novel locomotor phenotype in Drosophila melanogaster
*J. B. SLAWSON, E. A. KUKLIN, L. OSTROVSKY, L. C. GRIFFITH;
Biol., Brandeis Univ., Waltham, MA
In both vertebrates and invertebrates, experience-dependent plasticity is associated with the ability of CaMKII to become Ca2+-independent following autophosphorylation at residue T287. dCASK (the Drosophila homolog of mammalian CASK and C. elegans Lin-2) has been shown to regulate this phosphorylation event, thus modulating plasticity at the synapse. As expected from these findings, animals with lowered levels of dCASK due to large chromosomal deficiencies have been shown to be abnormal for some aspects of courtship plasticity and for habituation of the jump response. These flies also had a locomotor deficit, the cause of which is not yet understood. Using P-element mutagenesis, we have generated new and more precise null and hypomorphic alleles of dCASK. These animals have problems both in the initiation and maintenance of motor activity suggesting that dCASK is involved in basic locomotor function. We have also developed a motor habituation assay and are currently investigating the role of dCASK in this form of plasticity.


793.13/TT80. Communication among neurons in a thermosensory circuit in C. elegans
*S. M. WASSERMAN, D. BIRON, P. SENGUPTA;
Brandeis Univ., Waltham, MA
Organisms must sense and precisely encode external environmental stimuli in order to produce specific behavioral outputs. The movement of C. elegans on a spatial or temporal thermal gradient is dependent upon a memory of their previous cultivation temperature (TC). Specifically, C. elegans show predictable behaviors when placed at certain temperatures relative to their TC. When encountering temperatures higher than their TC, worms actively migrate down the gradient (cryophilic drive). When placed at temperatures below their TC worms show no biased directional movement (athermotactic behavior), and upon encountering temperatures around the TC, they perform isothermal tracking behavior. Memory of the TC is encoded in the threshold of both sensory responsiveness and synaptic output of thermosensory neuron(s). This memory can be reset upon exposure to a new temperature (Hedgecock & Russell, 1975; Biron et al., 2006). While several of the neurons and molecules involved in producing C. elegans thermotaxis behaviors are known, the manner in which these neurons communicate, both in order to set the memory of their TC, and to produce the behaviors described above, remains unclear. Moreover, it is unclear whether feedback from downstream interneurons modulate thermosensory neuron functions and setting of the TC memory. It has been suggested that thermosensory neurons in C. elegans communicate via glutamatergic signaling (Clark et al., 2007). Here, we further explore the role of molecules involved in glutamatergic signaling in mediating thermotaxis behavior. We also show that setting of the TC memory may require neuropeptide-mediated signaling, possibly from downstream interneurons. Mutations in a neuropeptide Y receptor-like GPCR localized to the axons of thermosensory neurons lead to defects in TC setting, although resetting of the TC follows normal kinetics. Preliminary imaging of calcium levels in thermosensory neurons also indicates defects in setting the TC threshold. Other thermosensory behaviors such as the cryophilic drive are weakened while atheromotactic behavior remains unaffected. We hypothesize that this neuropeptide Y receptor-like GPCR may be part of a feedback mechanism used by thermosensory neurons to set the memory of the TC. Our goal is to further explore the roles of this neuropeptide and glutamatergic signaling pathways in order to understand how neurons in a circuit communicate to execute precise behaviors.


815.7. Effects of memory load, syntactic complexity and age on cognitive effort: a pupillometry study
*T. PIQUADO, D. ISAACOWITZ, A. WINGFIELD;
Brandeis Univ., Waltham, MA
The motivation underlying these experiments lies in the notion that the extra effort (resource-demand) necessary for successful verbatim recall under conditions of effortful listening due to reduced hearing acuity in older adults, may come at the cost of resources that might otherwise be available for downstream cognitive operations such as comprehending sentences with difficult syntax. To the extent that older adults already begin with reduced resources relative to young adults, age might produce a multiplicative effect.
Although we and others have made the argument that older adults use extra effort, the evidence has rested on inference drawn from performance; that is, that memory performance is poorer under conditions when syntactic comprehension of the to-be-recalled sentences was possible but required extra perceptual effort. We chose to use pupillometry to demonstrate this cognitive effort since task-evoked pupillary responses have been considered a sensitive psychophysiological index of effortful activity.
In one experiment, we examined processing effort signaled by a listener's pupil size while listening and recalling lists of digits. Young and healthy older adults heard lists of random digits, four, six or eight digits in length, followed by a two-second retention interval, then a tone was heard, at which point they were to attempt to recall the digits aloud in order (serial recall). Pupil size over the duration of each trial was measured using infrared eye-tracking at a 60Hz sampling rate.
In the second experiment our interest was in effortful processing associated with syntactically complex sentences and memory load. This was done by contrasting sentences with subject-relative clause structure (e.g., The dog that scared the cat hopped the fence), which is fairly straight forward versus object-relative clause structure (e.g., The dog that the cat scared hopped the fence), which is more complex. Working memory load was independently varied by adding modifiers. In addition to filler sentences, the four main conditions were: (1) subject-relative without modifiers, (2) subject-relative with modifiers, (3) object-relative without modifiers and (4) object-relative with modifiers. The participants were asked to listen, wait for a tone, then recall aloud the sentence verbatim.
These experiments demonstrated in young and older adults that (1) pupil diameter increases in size progressively while listening, reaches its peak during the pause interval and then decreases during recall, (2) pupil diameter increases in size differentially in response to more demanding sentences and (3) older adults’ change in pupil size was performance-dependent.


860.11/JJ2. Immediate compensation for variations in self-generated Coriolis forces related to body dynamics and carried objects
*P. PIGEON1, J. R. LACKNER1,2, P. DIZIO1,2;
1Ashton Graybiel Lab., 2Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA
We have previously shown that Coriolis and centripetal forces result when an arm movement is performed during trunk rotation and that these forces produce large trajectory deviations during passive, constant velocity trunk rotation but do not affect movement trajectory during normal, voluntary turn and reach (T&R) movements. Here, we studied the accuracy of T&R movements when the Coriolis forces that were generated were augmented by having the subjects hold a 454g object in their hand. The consequence of holding the weight is to magnify the effect of the Coriolis force by increasing the effective inertial mass of the arm. We were also interested in whether there would be equal performance for the left and right arm. Subjects made slow and fast voluntary T&R movements to targets either with their right arm during counterclockwise rotation, or their left arm during clockwise rotation, with and without the weight in their hand. The targets were arranged in mirror image locations for left- and right-handed reaches. The entire experiment was conducted in darkness except for the target lights, which were extinguished at movement onset. Movement endpoints were equally accurate at both speeds, with either hand, and in both weight conditions. The trajectories to targets requiring substantial trunk rotation were straighter when performed at higher speeds but slightly more deviated when subjects held the weight. There were no significant effects on trajectory curvature of the hand used. Subjects did not slow their torso velocity or change the relative timing of the peaks of arm and torso velocity when holding the weight, although there was a slight decrease in their hand velocity relative to the torso. Overall, these results suggest that they did not alter movement coordination to minimize the effects on Coriolis force magnitudes of holding the weight. These results indicate that compensations for forthcoming Coriolis force variations take into account the dynamic properties of the body and of external objects, as well as the planned velocities of the torso and arm.


861.3/JJ17. Moving objects in microgravity
*A. PIEROBON1, D. PIOVESAN1, P. DIZIO1,2, J. R. LACKNER1,2;
1Ashton Graybiel Lab., 2Volen Ctr. for Complex Systems, Brandeis Univ., Waltham, MA
Carrying an object in a normal 1 g environment requires motor attunement to its weight and inertia. In a 0 g environment, objects have mass but no weight. How do we accommodate when moving weightless objects with different masses?
Eight subjects (2 female, 6 male; age 45±16 years) participated in an experiment conducted in parabolic flight. They performed planar reaching movements with their right hand while grasping a light or a heavy object in the microgravity phases of 20 consecutive parabolas, and they remained as immobile as possible at all other times. Each parabola lasted about 20 s, and subjects made about 4 movements per parabola. The subjects were strapped in a standard aircraft seat with a portable horizontal table attached to its armrests. Movements started from a common position and were directed towards either a target 23cm straight ahead or one 38cm at a 55° diagonal (leftward). For the first 2 parabolas, movements were performed while grasping a hollow, 30g, 2.5cm diameter, plastic cylinder, and the next 15 parabolas were done while grasping a 500g cylinder which appeared identical. We then took away the 500g object and returned the 30g object. Subjects were aware of the switch, but were not allowed to handle the restored 30g object until the moment of reach onset, in microgravity
The first movement made with the restored 30g object showed a deviation of its trajectory along the vertical axis. A variation of average forward velocity was also evident when shifting from higher to lower mass. The variation of average velocity after switching to the lighter object is consistent with persistence of an accommodation to the inertia of the heavier object in the movement plane. However, the vertical trajectory deviation is out of proportion with what would be expected from the variation of the inertia alone in the absence of a gravitational field. A possible explanation is that compensation of static loads and dynamic planning are inherently linked. Long term exposure to microgravity might be required to uncouple trajectory control from gravity.


878.13/SS63. Expectation of reward modulates responses in rat primary visual cortex
*H. O. GALPERIN, B. L. WHITE, J. FISER;
Brandeis Univ., Waltham, MA
Classical views of information flow in primary visual cortex suggest that orientation information is encoded early in a feed-forward architecture and passed to higher levels of cortex for further processing. More recent studies suggest that top-down information can modulate processing of even basic visual attributes. We investigated whether responses in primary visual cortex are modulated by top-down effects evoked by differential rewarding of oriented grating stimuli. Multiunit extracellular recordings were obtained using microwire electrodes chronically implanted in rat primary visual cortex while grating stimuli were presented under different reward conditions. Awake headfixed animals viewed alternating +45° and -45° sinusoidal grating stimuli. During a control sessions, gratings were passively presented with no reward. In three subsequent sessions, one grating (CS+) was paired with a water reward while the other grating (CS-) remained unrewarded. On the third rewarded session, units showed a two-fold increase in firing that plateaued and then returned to baseline during the CS+, while firing rates for the CS- remained constant across sessions. These results suggest a more complex model of visual processing where top-down contextual information strongly and continuously influences stimulus-specific bottom-up processes at even the earliest stages of visual processing.