email huangj@cshl.edu, phone (516) 367-8388, fax (516) 367-6805

We are studying the cellular and molecular mechanisms underlying the construction and plasticity of GABAergic inhibitory circuits in the mammalian brain. GABAergic interneurons are essential components of neural networks and are crucial in all aspects of neural computation. GABAergic circuits consist of a rich array of cell types with distinct morphology, physiological properties, and synaptic connectivity. A prominent feature of GABAergic connectivity is the targeting of different classes of inhibitory synapses to subcellular compartments of principal neurons (i.e. spines, dendrite, soma, and axon initial segment), which allows differential regulation of the input, integration, and output of principal neurons. By combining state-of-the-art mouse genetics and high resolution imaging, we are beginning to define the mechanism of synapse targeting. We have identified a family of immunoglobulin cell adhesion molecules, which are distributed as "molecular labels" along subcellular compartments of principal neurons and direct GABAergic synapse targeting.

We have shown that, following subcellular synapse targeting, the maturation of GABAergic connections in the visual cortex is regulated by sensory experience during a postnatal critical period. By combining both in vivo and in vitro systems, we are exploring the role of GABA transmission, neurotrophins, and cell adhesion molecules in the activity-dependent maturation and function of GABAergic synapses. In addition, we are studying the mechanism by which GABAergic transmission regulates the timing and progression of critical period of plasticity. Our studies have direct implications in neurological and psychiatric illness such as autism and schizophrenia, which involve altered development and function of GABAergic circuits.

Please visit the Huang Lab home page.

Selected Publications

DiCristo, G., Chattopadhayaya, B., Kuhlman, S., Fu, Y., Wu, C., Rutishausser, U., Maffei L., Huang, Z.J. 2007 Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plasticity. Nature Neuroscience. 10:1569-77.

Chattopadhayaya, B., DiCristo, G., Wu, C., Kuhlman, S., Palmiter, R.D., Huang, Z.J. 2007 GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex. Neuron 54: 889-903.

Sugino, K., Hempel, C.M., Miller, M.N., Hattox, A.M., Shapiro, P., Wu, C., Huang, Z.J., and Nelson, S.B. 2006. Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Nat. Neurosci. 9: 99-107.

Ango, F., Di Cristo, G., Higashiyama, H., Bennett, V., Wu, P., and Huang, Z.J. 2004. Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment. Cell 119: 257–272.

Chattopadhyaya, B., Di Cristo, G., Higashiyama, H., Knott, G.W., Kuhlman, S.J., Welke, E., and Huang, Z.J. 2004. Experience and activity-dependent maturation of perisomatic GABAergic innervation in primary visual cortex during a postnatal critical period. J. Neurosci. 24: 9598–9611.