Project 3 Genetic Analysis of Visual Cortical Plasticity

University Of California Los Angeles, Los Angeles CA

Investigators

Linked publications & trials

Abstract

To identify genes required specifically for neocortical plasticity, we will focus on the activity-dependent[unreadable] plasticity of responses to the two eyes in the primary visual cortex during the critical period. We will screen[unreadable] memory mutants selected as likely to be defective in cortical plasticity in Project 1 for deficits in this form of[unreadable] visual cortical plasticity. We will use monocular visual deprivation during the critical period to induce[unreadable] plasticity, and test the mice with microelectrode recordings and intrinsic signal optical imaging methods[unreadable] recently developed in our laboratory. We will then study in detail by the methods noted below mutants that[unreadable] affect plasticity in both somatosensory (Project 2) and visual (this project, Project 3) cortex. Therefore, we[unreadable] will coordinate the sequence of mutant studies in projects 2 and 3 so that mutants that do not affect either[unreadable] visual or somatosensory plasticity can be set aside. The next series of experiments on selected mutant[unreadable] genes will focus on the development of cortical maps and the receptive field properties of individual neurons.[unreadable] Mutations that do not perturb the early development of the cortex and visual responses but do alter cortical[unreadable] plasticity will be the subject of detailed analysis. We will search for the basis of of plasticity defects in the[unreadable] selected mutants by measuring their the effects on the turnover of dendritic spines and synaptic boutons in[unreadable] vivo and the change in this turnover elicited by stimuli that would normally cause plasticity of visual[unreadable] responses. Because the appropriate regulation of intracortical inhibition is known to be a crucial regulator of[unreadable] visual cortical plasticity, we will also determine the effects of selected mutations on inhibitory[unreadable] neurotranmission by making whole cell patch recordings in vitro.[unreadable] These studies will identify novel genetic pathways that are specifically involved in neocortical plasticity.[unreadable] Nearly all of earlier research on genes involved in forebrain plasticity has begun from defects in plasticity in[unreadable] the hippocampus. We are selecting mutants in which hippocampal function should be normal. Defects in[unreadable] neocortical plasticity are likely to underly defects in cognition and awareness that underly many forms of[unreadable] mental illness and neurobehavioral developmental disorders. Identification of genetic pathways in[unreadable] experimental animals will be a first step toward understanding them and formulating rational therapy for[unreadable] these afflictions.