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Sacha B. Nelson
Professor of Biology
Physiological genomics of the mammalian neocortex

M.D./Ph.D., University of California, San Diego

contact information
(781) 736-3181

Nelson/Turrigiano Lab Home Page

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:

Sjostrom 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]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Varela J.A., S. Song, G.G. Turrigiano, and S.B. Nelson (1999) Differential depression at excitatory and inhibitory synapses in visual cortex. J. Neurosci. 19: 4293-4304. [abstract]

Chance F., S.B. Nelson, and L.F. Abbott (1999) Complex cells as cortically amplified simple cells. Nature Neuroscience, 2:277-282. [abstract]

Turrigiano G.G., K.R. Leslie, N.S. Desai, L.C. Rutherford, and S.B. Nelson (1998) Activity-dependent scaling of quantal amplitude in neocortical pyramidal neurons. Nature 391: 892-895. [abstract]

Nelson, S.B. and G.G. Turrigiano (1998): Synaptic depression: a key role in the cortical balancing act. Nature Neuroscience 1:539-541. [abstract]

Moore C.I. and S.B. Nelson (1998) Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J. Neurophysiol. 80:2882-2892. [abstract]

Chance F., S.B. Nelson, and LF Abbott (1998) Synaptic depression and the temporal response characteristics of V1 Cells. J. Neurosci. 18:4785-4799. [abstract]

Varela J.A., K. Sen, J. Gibson, J. Fost, L.F. Abbott, and S.B. Nelson (1997) A quantitative description of short-term plasticity at excitatory synapses in layer 2/3 of rat visual cortex. J. Neurosci. 17:7926-7940. [abstract]

Abbott, L.F., K. Sen, J. Varela, and S.B. Nelson 1997. Synaptic depression and cortical gain control. Science 275: 220-224. [abstract]

View Complete Publication List on PubMed: Sacha Nelson

Last update: February 6, 2007. E-mail comments or questions to the webmaster.