Cortical inhibitory interneurons (INs) play a critical role in shaping and balancing neuronal activity, and thus have been implicated in brain disorders such as epilepsy, autism, and schizophrenia. They display diverse subtypes, which differ in morphology, physiology, and connectivity. Such cell type diversity is thought to be essential for various types of circuit operations. Therefore, elucidating development, connectivity, and function of IN subtypes is crucial to understanding principles of the brain construction and function in normal and disease brains. To address these questions, we employ mouse genetics, molecular biology, virology, and imaging techniques. We are working on the following specific projects:
1) Molecular mechanisms underlying the specification and circuit formation of chandelier cells (ChCs), which powerfully control action potential generation in excitatory principal neurons (PNs) by innervating their axon initial segments. We have already identified several candidate genes that are preferentially expressed in ChCs. We are analyzing the function of these genes in vivo.
2) We have developed a novel genetic strategy, which enables us to label and manipulate IN subtypes sending inputs to PN subtypes. We will determine the spatial organization and function of IN subtypes in cortical microcircuits. We will also elucidate mechanisms underlying the organization of IN subtypes innervating area- and layer-specific PNs.