The mammalian neocortex is an organ of stunning complexity that plays an indispensable role in many human behaviors. Despite a century of anatomical work and a half-century of neurophysiology, the cell types that comprise neocortical circuits are incompletely defined. We have recently begun using molecular genetic approaches to identify markers for subtypes of cortical neurons and to explore changes in gene expression that accompany alterations in cortical circuits induced by experience or by disease states. We identify neurons both anatomically – using fluorescent tracers, and brain dissection, and genetically – using strains of mice in which GFP expression is driven by cell-type specific promoters. RNA from as few as 30 neurons can be isolated, amplified, and hybridized to Affymetrix microarrays. Using this approach we have found dramatic differences between different subtypes of cortical neurons in expression of transcription factors, signaling molecules (such as channels and receptors), and other cell surface molecules, such as lectins. Currently we are developing bioinfomatic tools to find candidate upstream and downstream regulatory sequences that direct regional and cell-type specific expression. We are also trying to determine how the profile of genes expressed gives rise to each cell-type’s electrophysiological and anatomical phenotype. Examining brain gene expression in a cell-type specific way may also provide a more sensitive assay for changes in gene expression that occur as a result of experience or in response to disease states. We are currently studying the physiological and transcriptional effects of visual experience on pyramidal neurons and GABAergic interneurons. In collaboration with the Jaenisch lab at the Whitehead Institute we are also studying the physiological consequences of the loss of the transcriptional repressor MECP2 in a mouse model of Rett’s Syndrome, a genetic cause of mental retardation.

 

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Selected Publications:

Reduced excitatory connectivity but intact long-term potentiation in a mouse model of Rett Syndrome. Dani V.S. and Nelson S.B. (2009) J. Neurosci. In Press.

Transcriptional and electrophysiological maturation of neocortical fast-spiking GABAergic interneurons. Okaty BW, Miller MN, Sugino K, Hempel CM, Nelson SB. J Neurosci. 2009 May 27;29(21):7040-52. [abstract]

Genome-wide identification of targets of the drosha-pasha/DGCR8 complex. Kadener S, Rodriguez J, Abruzzi KC, Khodor YL, Sugino K, Marr MT 2nd, Nelson S, Rosbash M. RNA. 2009 Apr;15(4):537-45. Epub 2009 Feb 17. [abstract]

Region-specific spike-frequency acceleration in layer 5 pyramidal neurons mediated by Kv1 subunits. Miller MN, Okaty BW, Nelson SB. J Neurosci. 2008 Dec 17;28(51):13716-26. [abstract]

Strength through diversity. Nelson SB, Turrigiano GG. Neuron. 2008 Nov 6;60(3):477-82. Review. [abstract]

The Fezf2-Ctip2 genetic pathway regulates the fate choice of subcortical projection neurons in the developing cerebral cortex. Chen B, Wang SS, Hattox AM, Rayburn H, Nelson SB, McConnell SK. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11382-7. [abstract]

A manual method for the purification of fluorescently labeled neurons from the mammalian brain. Hempel CM, Sugino K, Nelson SB. Nat Protoc. 2007;2(11):2924-9. [abstract]

Layer V neurons in mouse cortex projecting to different targets have distinct physiological properties. Hattox AM, Nelson SB. J Neurophysiol. 2007 Dec;98(6):3330-40. [abstract]

Sjöström PJ, Turrigiano GG, Nelson SB. (2007) Multiple forms of long-term plasticity at unitary neocortical layer 5 synapses. Neuropharmacology. 2007 Jan;52(1):176-84. [abstract]

Nelson SB, Hempel C, Sugino K. (2006) Probing the transcriptome of neuronal cell types.Curr Opin Neurobiol. 2006 Oct;16(5):571-6. Epub 2006 Sep 7. Review. [abstract]

Maffei A, Nataraj K, Nelson SB, Turrigiano GG. (2006) Potentiation of cortical inhibition by visual deprivation. Nature. 2006 Sep 7;443(7107):81-4. Epub 2006 Aug 23. [abstract]

Nelson SB, Sugino K, Hempel CM. (2006) The problem of neuronal cell types: a physiological genomics approach.Trends Neurosci. 2006 Jun;29(6):339-45. Review. [abstract]

The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Chang Q, Khare G, Dani V, Nelson S, Jaenisch R. (2006) Neuron. 2006 Feb 2;49(3):341-8. [abstract]

Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Sugino K, Hempel CM, Miller MN, Hattox AM, Shapiro P, Wu C, Huang ZJ, Nelson SB. (2006) Nat Neurosci. 2006 Jan;9(1):99-107. Epub 2005 Dec 20. Erratum in: Nat Neurosci. 2006 Feb;9(2):292. [abstract]

Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome. Dani VS, Chang Q, Maffei A, Turrigiano GG, Jaenisch R, Nelson SB. (2005) Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12560-5. [abstract]

Highly nonrandom features of synaptic connectivity in local cortical circuits. Song S, Sjöström PJ, Reigl M, Nelson S, Chklovskii DB. (2005) PLoS Biol. 2005 Mar;3(3):e68. Epub 2005 Mar 1. Erratum in: PLoS Biol. 2005 Oct;3(10):e350.

Selective reconfiguration of layer 4 visual cortical circuitry by visual deprivation. Maffei A, Nelson SB, Turrigiano GG. (2004) Nat Neurosci. 2004 Dec;7(12):1353-9. [abstract]

Endocannabinoid-dependent neocortical layer-5 LTD in the absence of postsynaptic spiking. Sjöström PJ, Turrigiano GG and Nelson SB. (2004) J Neurophysiol. 2004 Dec;92(6):3338-43. [abstract]

A proportional but slower NMDA potentiation follows AMPA potentiation in LTP. Watt AJ, Sjöström PJ, Hausser M, Nelson SB, Turrigiano GG. (2004) Nat Neurosci. [abstract]

Homeostatic plasticity in the developing nervous system. Turrigiano GG, Nelson SB. (2004) Nat Rev Neurosci. 5:97-107.

Activity dependent remodeling of presynaptic inputs by postsynaptic expression of activated CaMKII. Pratt KG. Watt A.J, Griffith LC. Nelson SB, and Turrigiano GG (2003) Neuron 39:269-281. [abstract]

The NMDA to AMPA ratio at synapses onto layer 2/3 pyramidal neurons is conserved across prefrontal and visual cortices. Myme C, Sugino K, Turrigiano GG and Nelson SB (2003) J. Neurophysiol. 90:771-779. [abstract]

Neocortical LTD via coincident activation of presynaptic NMDA and cannabinoid receptors. Sjöström PJ, Turrigiano GG, and Nelson SB (2003) Neuron 39:641-654 (see also Preview 579-581). [abstract]

Receptive field properties and laminar organization of lateral geniculate nucleus in the gray squirrel (Sciurus carolinensis). Van Hooser SD, Heimel JA. and Nelson SB (2003) J Neurophysiol. 90:3398-418.

Nelson SB and Van Hooser S (2003) Visual System. Encyclopedia of Life Sciences, Macmillan Ref. Ltd .

Rate and timing in cortical synaptic plasticity. Nelson SB, Sjöström PJ and Turrigiano GG (2002) Phil Trans R Soc Lond B 357:1851-1857. [abstract]

Cortical circuits: diverse or canonical? Nelson SB (2002)Neuron 36: 19-27.

Temporal dynamics of biological synapses. Abbott LF, and Nelson SB (2002) Arbib, M., ed. The Handbook of Brain Theory and Neural Networks - Second Edition, Bradford MIT Press, Cambridge, pp. 1156-1158.

Multi-unit spike-triggered averaging: a method for probing the physiology of central synapses. Hempel CM, Sugino K and Nelson SB (2002) J. Neurosci. Meth. 120: 121-129. [abstract]

Critical periods for experience-dependent synaptic scaling in visual cortex. Desai NS, Cudmore RH, Nelson SB, Turrigiano GG. (2002) Nat Neurosci. [abstract]

Spike timing, calcium signals and synaptic plasticity. Sjöström PJ, Nelson SB. (2002) Curr Opin Neurobiol. 2002 Jun;12(3):305-14. [abstract]

Short-term depression at thalamocortical synapses contributes to rapid adaptation of cortical sensory responses in vivo. Chung S, Li X, Nelson SB. (2002) Neuron. 34(3):437-46. [abstract]

Fast propagation of firing rates through layered networks of noisy neurons. van Rossum MC, Turrigiano GG, Nelson SB. (2002) J Neurosci. 22(5):1956-66. [abstract]

Rate, timing, and cooperativity jointly determine cortical synaptic plasticity. Sjöström PJ, Turrigiano GG, Nelson SB. (2001) Neuron. Dec 20;32:1149-64. [abstract]

Synaptic plasticity: taming the beast. Abbott LF, Nelson SB. (2000) Nat Neurosci. 3 Suppl:1178-83. [abstract]

Activity coregulates quantal AMPA and NMDA currents at neocortical synapses. Watt AJ, van Rossum MC, MacLeod KM, Nelson SB, Turrigiano GG. (2000) Neuron. 26(3):659-70. [abstract]

Hebb and homeostasis in neuronal plasticity. Turrigiano GG, Nelson SB. (2000) Curr Opin Neurobiol. 10(3):358-64. [abstract]

Multiple forms of short-term plasticity at excitatory synapses in rat medial prefrontal cortex. Hempel CM, Hartman KH, Wang XJ, Turrigiano GG, Nelson SB (2000) J Neurophysiol. 83(5):3031-41. [abstract]

 

View Complete Publication List on PubMed: Sacha Nelson

 

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Last update: July 27, 2009.