Matthew S. Lazarus

2nd Year Graduate Student

Department: Cold Spring Harbor Laboratory

Graduate Program: Neuroscience

Advisor: Josh Huang

Abstract:

Advisor: Dr. Z. Josh Huang, Cold Spring Harbor Laboratory

Title: Role of GAD67 and GAD65 in the functional maturation of inhibitory transmission in primary visual cortex

Matthew S. Lazarus, Z. Josh Huang

Cortical inhibitory interneurons are a diverse group of cells that provide precise control over the activity of local brain circuits. The importance of inhibitory interneurons has been demonstrated by studies of cortical plasticity and development, and by the observation of inhibitory defects in psychiatric disorders. The heterogeneity of these cells has previously made them difficult to study, however recent advances are beginning to allow for a more careful investigation of these cells and the the circuits they form. We will use modern genetic and electrophysiological techniques to study the development of specific classes of cortical inhibitory interneurons during the critical period for ocular dominance (OD) plasticity, a canonical model of cortical plasticity. We will focus on two non-overlapping classes of cortical interneurons: Parvalbumin expressing cells, which have a fast-spiking phenotype and provide proximal inhibition to or near to the cell body, and somatostatin expressing cells, which have a regular-spiking phenotype and provide distal inhibition to the dendrites. The activity-dependence of inhibitory circuit formation will be studied by manipulating the two glutamic acid decarboxylase enzymes, the 65 and 67 kilodalton isoforms (GAD65 and GAD67, respectively), that synthesize the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Both of these enzymes have been shown to affect cortical development. Knockout of GAD65 prevents the occurrence of OD plasticity, whereas GAD67 regulates the morphological maturation of interneurons. In particular, GAD67 deficiency has been repeatedly demonstrated in schizophrenia. We will investigate the role of these enzymes in the functional maturation of specific classes of inhibitory interneurons. The knowledge gained from this study will help develop an understanding of how inhibition affects cortical plasticity and learning, and how dysfunction of the inhibitory system can contribute to a pathological state.