Matthew S. Lazarus

2nd Year Graduate Student

Department: Cold Spring Harbor Laboratory

Graduate Program: Neuroscience

Advisor: Josh Huang

Abstract:

Title: Using mini-IPSC recordings to determine the functional effects of GAD67 knockout

Matthew Lazarus, Z. Josh Huang

Inhibitory interneurons play a vital role in the functioning of neural circuits, and provide for a great deal of complexity and flexibity in the neocortex. Aberrant functioning of inhibitory circuits has been implicated in the pathophysiology of epilepsy, schizophrenia, and autism spectrum disorders. However, the mechanisms underlying the development of these circuits are still not completely understood. The rate limiting enzyme of GABA synthesis, GAD67, has been shown to have activity-dependent regulation, and to affect cell proliferation, neurite growth, and adult neurogenesis. Knockdown of the gene that encodes GAD67, Gad1, has resulted in alterations of both wiring and transmission in inhibitory circuits, leading to morphological changes, as well as decreased overall GABA levels. The functional effects of these alterations have yet to be thoroughly studied. We will examine the physiology of these altered cortical circuits in Gad1+/- mice, using recordings of miniature inhibitory post-synaptic currents (mini-IPSCs) in voltage-clamped layer 2/3 pyramidal neurons in mouse primary visual cortex. The frequency of mini-IPSCs provides information about the number of inhibitory synapses onto pyramidal neurons, while the amplitude of mini-IPSCs provides information on the strength of these synapses. We will follow the development of inhibitory circuits before, during, and after the critical period for ocular dominance plasticity.