Molecular Cytoarchitecture of Central Visual Areas

Hockfield, Susan

Abstract

A major question in neuroscience is how differences in neuronal phenotype are achieved and maintained. The acquisition of mature, differentiated properties takes place over an extended period, through both intrinsic cell programs and activity-dependent processes. Over the last several years, this laboratory has asked whether differences in neuronal cell surface proteins might parallel structural or functional properties. In earlier work, we described one cell surface protein that is expressed on functionally related subsets of neurons in central visual areas. During the current period, additional members of this family were identified. In addition, new experimental approaches were developed that permit the function of these cell surface proteins to be studied. The major goal of this project is to understand the regulation of expression and the function of cell surface proteins that are differentially expressed on neuron in central visual areas. The proposed work has three specific aims: 1: to determine if neuronal surface proteoglycans play a role in synapse formation. Neuronal chondroitin sulfate proteoglycans(CSPGs) are expressed on the surface of restricted subsets of neurons. On the neuronal cell membrane, they are distributed over non-synaptic regions and are excluded from regions of synaptic contact. The proposed experiments will ask if neuronal CSPGs determine the sites of initial synapse formation. 2. To investigate how activity regulates the expression of neuronal CSPGs. The acquisition of normal levels of neuronal cell surface CSPGs in adult animals requires normal pattern of activity during early life. The regulation of cell surface CSPGs by early activity parallels the regulation of structural and functional properties of neurons by early activity. Here, the role of neurotransmitter receptors and growth factors in regulating the expression of CSPGs will be tested. 3. To clone the gene(s) for neuronal cell surface proteoglycans. Neuronal cell surface proteoglycans show a remarkable degree of heterogeneity and cell-type specificity. To determine the genetic basis for this heterogeneity, and to understand the molecular mechanisms underlying their cell-type specific expression and activity-dependent regulation, the genes encoding neuronal, the genes encoding neural CSPGs will be cline. Our long-term goal is to understand the cellular and molecular mechanisms could aid in the recovery from neurological or ophthalmological diseases or injury.