Cold Spring Harbor Laboratory
PhD, 1994, Brandeis University
Phone: (516) 367-8388
We are studying the cellular and molecular mechanisms underlying the development and experience-dependent plasticity of the GABAergic circuits in neocortex. GABAergic interneurons control neuronal excitability and information processing at precise spatial and temporal domains. The functional maturation of GABAergic inhibition in visual cortex is regulated by sensory experience and in turn contributes to the critical period of ocular dominance plasticity. A fascinating yet puzzling feature of cortical GABAergic circuits is the rich array of interneuron cell types, which display remarkably distinct morphology, physiological properties, synaptic connectivity patterns, and gene expression profiles. Using cell type-specific promoters, we have generated an array of bacterial artificial chromosomes (BAC) transgenic mice in which defined GABAergic cell types are labeled with GFP at unprecedented resolution. These mice thus allow us to reliably study the maturation of physiological properties and synaptic transmission of defined GABAergic circuits during the critical period and following visual deprivation. Two photon laser scanning microscopy allows us to image GABAergic presynaptic boutons and to characterize the development and plasticity of GABAergic innervation in cultured and acute brain slices. We are especially interested in how neurotrophic factors, such as BDNF, regulate the innervation and synaptic transmission of GABA interneurons. Finally, using BAC transgenics we manipulate the function of specific classes of GABAergic circuits to test their roles in critical period plasticity. We hope to elucidate the molecular basis of the development and plasticity of GABAergic circuits at the level of defined cell types and synapses.
- Laboratory Personnel
- Cristo GD, Wu C, Chattopadhyaya B, Ango F, Knott G, Welker E, Svoboda K, Huang ZJ. Subcellular domain-restricted GABAergic innervation in primary visual cortex in the absence of sensory and thalamic inputs. Nat Neurosci. 2004 Nov;7(11):1184-6. Epub 2004 Oct 10.
- Ango F, di Cristo G, Higashiyama H, Bennett V, Wu P, Huang ZJ. Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment. Cell. 2004. Oct 15;119(2):257-72.
- Chattopadhyaya B, Di Cristo G, Higashiyama H, Knott GW, Kuhlman SJ, Welker E, Huang ZJ. Experience and activity-dependent maturation of perisomatic GABAergic innervation in primary visual cortex during a postnatal critical period. J Neurosci. 2004 Oct 27;24(43):9598-611.
- Gianfranceschi, L., Walls, J., Morales, B., Tonegawa, S., Kirkwood, A. Huang, ZJ., and Maffei, L. BDNF overexpression rescues the effects of dark rearing on the development of critical period in visual cortex. PNAS (in press).
- Huang, Z.J., Yu, W., Lovett, C., and Tonegawa, S. (2002). A Cre / LoxP recombination activated neuronal marker system in the mouse neocortex and hippocampus. Genesis 32(3):209-217.
- Huang, Z.J., Kirkwood, A., Bear, M., Pizzurusso, T., Porciatti, V., Maffei, L., and Tonegawa, S. (1999). BDNF Regulates the Maturation of Inhibition and the Critical Period Plasticity in Mouse Visual Cortex. Cell. 98 (6): 739-755.
- Huang, Z.J., Curtin, K., and Rosbash, M. (1995). Period protein interactions and temperature compensation of a circadian clock in Drosophila melanogaster. Science 267:1169-1172.
- Huang, Z.J., Edery, I., and Rosbash, M. (1993). PAS is a novel dimerization domain shared by the Drosophila period protein and several transcription factors. Nature 364:259-262.
- Ango, F. - Postdoctoral Fellow
- deCristo, G. - Postdoctoral Fellow
- Chattopadhyaya, B. - Graduate Student
- Kuhlman, S. - Postdoctoral Fellow
- Chiariello, C - Graduate Student
- Pal, T. - Lab Tech I
- Wang, Q. - Postdoctoral Fellow