Z. Josh Huang
Ph.D., Brandeis University, 1994
We study the developmental assembly and functional organization of neural circuits in the cerebral cortex that process information and guide behavior. We combine molecular, anatomical and physiological approaches, with the entry point from a systematic identification of neuronal cell types using genetically engineered mice. Our study has implications in understanding neuropsychiatric disorders such as schizophrenia and autism.
Josh Huang and colleagues study the assembly and function of neural circuits in the neocortex of the mouse. The neocortex consists of a constellation of functional areas that form a representational map of the external (sensory, social) and internal (visceral, emotional) world. These areas are strategically interconnected into processing modules and subnetworks that are integrated into global brain systems. This elaborate yet highly organized neural infrastructure supports dynamic circuit operations that process information and guide intelligent behavior. The group’s overarching hypothesis is that, at the cellular level, cortical processing streams and output channels are mediated by a large set of distinct glutamatergic pyramidal neurons (PyNs), and functional PyN ensembles are regulated by a diverse yet distinct set of GABAergic interneurons (INs). The issue of neuronal cell type identity and diversity in neocortex is a starting point for conceptual and technical progress.
The Huang lab systematically builds cell type genetic tools that integrate a full set of modern techniques toward understanding the basic neocortex architecture. Building on their success in genetic targeting of GABA INs, they have recently extended this effort to PyNs. Experimental access to an increasing set of cell types provides unprecedented opportunities to study the developmental assembly and functional organization of specific cortical circuits underlying behavioral function. Their current research program begins to integrate studies of GABA INs and PyNs. Among GABA interneurons, the chandelier cell is one of the most distinctive cell type that controls PyN firing at the axon initial segment. Huang and colleagues are studying the developmental specification of chandelier cells, their activity-dependent circuit integration, and their functional connectivity. Regarding pyramidal neurons, they are systematically characterizing the developmental origin, axon projection, and input connectivity of multiple classes of genetically defined PyN types, focusing on the forelimb motor cortex. They combine a range of approaches that include genetic and viral engineering, cell type gene expression, genetic fate mapping, imaging, electrophysiology, and behavior analysis. With these tools and progress, they begin to integrate their studies in the behavioral context of the motor cortex control of volitional forelimb movements and motor learning.
Taniguchi, H., Lu, J., and Huang, Z,J. 2013. The Spatial and Temporal Origin of Chandelier Cells in Mouse Neocortex. Science 339: 70–74.
He, M., Liu, Y., Wang, X., Zhang, M.Q., Hannon, G.J., and Huang, Z.J. 2012. Cell-type-based analysis of microRNA profiles in the mouse brain. Neuron 73: 35–48.
Taniguchi, H., He, M., Wu, P., Kim, S., Paik, R., Sugino, K., Kvitsani, D., Fu, Y., Lu, J., Lin, Y., Myoshi, G., Shima, Y., Fishell, G., Nelson, S., and Huang, Z.J. 2011. A Resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71: 995–1013.
DiCristo, G., Chattopadhayaya, B., Kuhlman, S., Fu, Y., Wu, C.Z., Rutishausser, U., Maffei., L., and Huang, Z.J. 2007. Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plasticity. Nat. Neurosci. 10: 1569–1577.
Ango, F., DiCristo, G., Higashiyama, H., and Huang, Z.J. 2004. An ankyrin-based subcellular gradient of the immunoglobulin cell adhesion protein neurofascin specifies GABAergic innervation at Purkinje axon initial segment. Cell 119: 257–272.
Scientists solve birth and migration mysteries of cortex’s powerful inhibitors, ‘chandelier’ cells
GABA signaling prunes back copious ‘provisional’ synapses during neural circuit assembly
CSHL team creates genetic ‘GPS’ system to comprehensively locate and track inhibitory nerve cells
Neuroscientists at CSHL show in unprecedented detail how cortical nerve cells form synapses with neighbors
One focus of our lab is the chandelier cell (ChC), a distinct type of inhibitory interneuron in the neocortex that may regulate neural circuit operations underlying information processing. Deficiency of ChCs is implicated in schizophrenia pathology. We seek to discover how altered ChC function contributes to behavioral deficits in schizophrenia.