My laboratory is interested in two questions: the mechanisms
of memory in the brain and the mechanisms of phototransduction
in photoreceptors. In both cases, we seek to determine how
chemical and electrical processes can work as a system to
perform physiological function.
We are using the rat brain slice to study activity-dependent
synaptic plasticity. Most recently, we found that plasticity
is greatly heightened during a cholinergically-induced theta-frequency
oscillation of the hippocampal network. As a step in this
direction, we have developed a means of monitoring individual
synapses in the dendrites using Ca2+-sensitive
dyes and optical detection methods. Theoretical studies
are also being done in an attempt to explore the possible
relationship of brain oscillations to memory events. Most
recently, it has become possible to test various theories
by measuring oscillations from the brain surface of patients
being treated for epilepsy. These patients are willing to
do standard memory tests and we can directly measure what
is going on in their brains during these tests.
 |
A related question of interest is the molecular basis of memory.
We have done theoretical work suggesting that the repository
of synaptic memory may be the calcium/calmodulin dependent
protein kinase II contained within a synaptic structure called
the postsynaptic density. There is now substantial support
for this model and we are attempting further tests. The processes
of synaptic plasticity are not fixed, but rather can be altered
by neuromodulators. Our recent work shows that dopamine can
affect both the strengthening and weakening of synapses.
In the area of phototransduction, a central problem is
the elucidation of the cascade reactions by which a single
photon absorbed by rhodopsin activates thousands of channels.
We have obtained evidence for the involvement of Ca2+
released by G protein, phospholipase-C, IP3 cascade. However,
we have evidence that the channels are directly opened by
cGMP. Thus, the current problem is to understand how cGMP
might be generated by Ca2+. This marvelous cascade
provides the opportunity to study other interesting reactions
such as modulation of rhodopsin deactivation and the role
of GTP hydrolysis.
Recent Publications:
Lisman JE. (2005) Hippocampus, II: memory connections.
Am J Psychiatry. 162:239.
Jensen O, Lisman JE. (2005) Hippocampal sequence-encoding
driven by a cortical multi-item working memory buffer. Trends
Neurosci. 28:67-72. [abstract]
Otmakhov N, Tao-Cheng JH, Carpenter S, Asrican B, Dosemeci
A, Reese TS, Lisman J. (2004) Persistent accumulation of
calcium/calmodulin-dependent protein kinase II in dendritic
spines after induction of NMDA receptor-dependent chemical
long-term potentiation. J Neurosci. 24:9324-31.
[abstract]
Otmakhova NA, Lisman JE. (2004) Contribution of Ih and
GABAB to Synaptically Induced Afterhyperpolarizations in
CA1: A Brake on the NMDA Response. J Neurophysiol.
92:2027-39 [abstract].
Raghavachari S, Lisman JE. (2004) Properties of Quantal
Transmission at CA1 Synapses. J Neurophysiol. 92:2456-67
[abstract].
Garger AV, Richard EA, Lisman JE., (2004) The excitation
cascade of Limulus ventral photoreceptors: guanylate cyclase
as the link between InsP3-mediated Ca2+ release and the
opening of cGMP-gated channels. BMC Neurosci.
5:7. [abstract]
Otmakhov N, Khibnik L, Otmakhova N, Carpenter S, Riahi
S, Asrican B, Lisman J. (2004) Forskolin-Induced LTP in
the CA1 Hippocampal Region Is NMDA Receptor Dependent. J
Neurophysiol. 91:1955-62. [abstract]
Lisman J, Lichtman JW, Sanes JR. (2003) LTP: perils and
progress. Nat Rev Neurosci. 4:926-9.
Lisman J. (2003) Actin's actions in LTP-induced synapse
growth. Neuron. 38:361-2.
Lisman J. (2003) Long-term potentiation: outstanding questions
and attempted synthesis. Philos Trans R Soc Lond B Biol
Sci. 358:829-42. [abstract]
Kepecs, A., Lisman, J., (2003) Information encoding and
computation with spikes and bursts., Network: Comput.
Neural Syst. 14:103-118 [abstract].
Conti, R., Lisman, J.: The high variance of AMPA receptor-
and NMDA receptor-mediated responses at single hippocampal
synapses: Evidence for multiquantal release, PNAS, April
15, 2003, 100(8):4885-4890 [abstract].
Graboi, D., Lisman, J., Recognition by top-down and bottom-up
processing in cortex: the control of selective attention,
April 17, 2003, Journal of Neurophysiology. [abstract]
Lisman, J., Long-term potentiation: Outstanding Questions/Attempted
Synthesis, Philosophical Transactions of the Royal Society
London B, (2003) 358, 829-842. [abstract]
Lisman, J.E., Richard, EA, Raghavachari, S, Payne, R.:
Simultaneous roles for Ca2+ in excitation and adaptation
of Limulus ventral photoreceptors, Advances in Experimental
Medicine and Biology, 2002; 514:507-538. [abstract]
Koulakov, A.A., Raghavachari, S., Kepecs, A., Lisman, J.E.:
Model for a Robust Neural Integrator., Nature Neuroscience,
August 2002, 5(8):775-782. [abstract]
Jensen, O., Gelfand, J., Kounios, J., Lisman, J.E.: Oscillations
in the Alpha Band (9-12 Hz) Increase with Memory Load during
Retention in a Short-term Memory Task., Cerebral Cortex,
August 2002, 12:877-882. [abstract]
Kepecs, A., Wang, X-J, Lisman, J., Bursting Neurons Signal
Input Slope, The Journal of Neuroscience, October 15, 2002,
22(20):9053-9062. [abstract]
Conti, R, Lisman, J.: A Large Sustained Ca2+ Elevation
Occurs in Unstimulated Spines During the LTP Pairing Protocol
But Does Not Change Synaptic Strength, Hippocampus 12(5):667-679,
2002. [abstract]
Lisman, J.E., Schulman, H., and Cline, H. (2002) The Molecular
Basis of CaMKII Function in Synaptic and Behavioural Memory.
Nature Reviews Neuroscience, 3:175-190. [abstract]
Otmakhova, N.A., Otmakhov N., and Lisman, J.E. (2002)
Pathway-Specific Properties of AMPA and NMDA-Mediated Transmission
in CA1 Hippocampal Pyramidal Cells, The Journal of Neuroscience,
22:1199-1207. [abstract]
Otmakhov, N., Lisman, J.E. (2002) Postsynaptic Application
of a cAMP Analogue Reverses Long-Term Potentiation in Hippocampal
CA1 Pyramidal Neurons., Journal of Neurophysiology
87:3018-3032. [abstract]
Chen, H.X, Otmakhov, N., Strack, S., Colbran, R.J., and
Lisman, J.E. (2001) Is Persistent Activity of Calcium/Calmodulin-Dependent
Kinase Required for the Maintenance of LTP? Journal of
Neurophysiology 85:1368-1376. [abstract]
Lisman, J.E. and Morris, G.M. (2001) Why is the cortex
a slow learner? Nature - News and Views: 411:248-249.
Lisman, J., Jensen, O., and Kahana, M. (2001) In Neuronal
Mechanisms of Memory Formation. (ed. Holscher, C.) 195-223
(Cambridge University Press, Cambridge, UK.
Garger, A., Richard, E., Lisman, J. (2001) Inhibitors of
guanylate cyclase inhibit phototransduction in Limulus
ventral photoreceptors. Visual Neuroscience, 18(4):625-32.
[abstract]
Chen, F. H., Baumann, A., Payne, R., Lisman, J.E. (2001).
A cGMP-gated channel subunit in Limulus photoreceptors.
Visual Neuroscience, 18(4):517-26 [abstract]
Kim, C.H. and Lisman, J.E. (2001). A Labile Component of
AMPA Receptor-Mediated Synaptic Transmission Is Dependent
on Microtubule Motors, Actin, and N-Ethylmaleimide-Sensitive
Factor. Journal of Neuroscience, 21:4188-4194.
[abstract]
Raghavachari, S., Kahana, M., Rizzuto, D., Caplan, J.,
Kirschen, M., Bourgeois, B., Madsen, J., Lisman, J. (2001).
Gating of Human Theta Oscillations by a Working Memory Task.
Journal of Neuroscience, 21:3175-3183. [abstract]
Lisman, J.E. and Zhabotinsky, A. M. (2001). A model of
synaptic memory: a CaMKII/PP1 switch that potentiates transmission
by organizing an AMPA-receptor anchoring assembly. Neuron,
31:191-201. [abstract]
Lisman, J.E. and Otmakhova, N.A. (2001). Storage, recall,
and novelty detection of sequences by the hippocampus: elaborating
on the SOCRATIC model to account for normal and aberrant
effects of dopamine. Hippocampus, 11(5):551-68.
[abstract]
Jensen O, Lisman JE. (2000) Position reconstruction from
an ensemble of hippocampal place cells: contribution of
theta phase coding. J Neurophysiol. 83(5):2602-9.
[abstract]
Otmakhova NA, Otmakhov N, Mortenson LH, Lisman JE. (2000)
Inhibition of the cAMP pathway decreases early long-term
potentiation at CA1 hippocampal synapses. J Neurosci.
20(12):4446-51. [abstract]
Otmakhova NA, Lisman JE. (2000) Dopamine, serotonin, and
noradrenaline strongly inhibit the direct perforant path-CA1
synaptic input, but have little effect on the Schaffer collateral
input. Ann N Y Acad Sci. 911:462-4.
Kovalchuk, Y., Eilers, J., Lisman, J. And Konnerth, A.
(2000) NMDA receptor-mediated subthreshold Ca2+ signals
in spines of hippocampal neurons. Journal of Neuroscience
20:1791-1799.
Otmakhova, N.A. and Lisman, J.E. (1999) Dopamine selectively
inhibits the direct cortical pathway to the CA1 hippocampal
region. J. Neuroscience 19:1437-1445. [abstract]
Lisman, J.E. (1999) Relating hippocampal circuitry to
function: recall of memory sequences by reciprocal dentate-CA3
interaction. Neuron 22:233-242. [abstract]
Chen HX, Otmakhov N, Lisman J. (1999) Requirements for
LTP induction by pairing in hippocampal CA1 pyramidal cells.
J Neurophysiol. 82(2):526-32. [abstract]
Kim CH, Lisman JE. (1999) A role of actin filament
in synaptic transmission and long-term potentiation. J
Neurosci. 19(11):4314-24. [abstract]
Lisman JE, Fellous JM, Wang XJ. (1998) A role for NMDA-receptor
channels in working memory. Nat Neurosci. 1(4):273-5.
Lisman, J. (1997) Bursts as a unit of neural information:
making unreliable synapses reliable. Trends In Neuroscience
20:38-43. [abstract]
Otmakhova, N. and Lisman, J.E. (1996) D1/D5 dopamine receptor
activation increases the magnitude of early long-term potentiation
at CA1 hippocampal synapses. J. Neuroscience 16:7478-7486.
[abstract]
Lisman, J. and Idiart, M.A.P. (1995) Storage of 7 ±
2 short-term memories in oscillatory subcycles. Science
267:1512-1515. [abstract]
Lisman, J., (1994) The CaM kinase II hypothesis for the
storage of synaptic memory. TINS 17: 406-412.
[abstract]
Huerta, P.T., and Lisman, J.E. (1993) Heightened synaptic
plasticity of hippocampal CA1 neurons during a cholinergically
induced rhythmic state. Nature 364: 723-725.
[abstract]
Shin, J., Richard, E.A., and Lisman, J.E. (1993) Ca2+
is an obligatory intermediate in the excitation cascade
of Limulus photoreceptors. Neuron 11: 845-855.
[abstract]
Last update: April 4, 2005. E-mail comments
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