It has been appreciated for over 30 years that visual experience during early postnatal development produces permanent modifications of the connectivity, physiology and function of the visual cortex. Besides the obvious relevance of this neural plasticity to the development of visual capabilities in humans and animals, it seems likely that similar processes form the basis for some forms of learning and memory in the adult brain. Considerable progress has been made in identifying the specific changes in visual cortex that result from rearing animals in different environments, but the detailed mechanisms that underlie these modifications have remained elusive. Recently, however, advances in our understanding of the receptor mechanisms that mediate synaptic excitation in the visual cortex during development have provided an exciting new opportunity to investigate the mechanisms of"""""""" experience-dependent brain modification. Our long-term goal is to elucidate these molecular mechanisms of experience-dependent cortical plasticity.
The specific aims of this project are to evaluate the contribution of two specific excitatory amino acid receptors to synaptic function and plasticity in visual cortex. The receptor types are the N-methyl-D-aspartate (NMDA) receptor, which we have already shown plays a role in visual cortical plasticity, and the """"""""metabotropic"""""""" glutamate receptor. which we have shown is functionally expressed at high levels only during the developmental critical period when changes in cortex are readily elicited by visual experience.
Specific aim 1 : Elucidation of the contribution of NMIDA receptors to visual cortical plasticity. In this project we will follow several leads suggested by our previous in vivo studies, and more recent work on long-term potentiation (LTP) in visual cortical slices. We will assess the specific requirements for LTP in the cells in different layers at different ages.
Specific aim 2 : Characterization of the development of the metabotropic glutamate receptors. In these studies we will use histochemical methods to localize EAA-stimulated PI turnover and the mRNA for the metabotropic receptor in the visual cortex at different ages. Lesion studies will be carried out to identify the source(s) of the receptors.
Specific aim 3 : Investigation of the function of the metabotropic receptor in visual cortex at different ages. In these studies we will use a selective agonist for the metabotropic receptor, cis-1 aminocyclopentane-1,3-dicarboxylic acid (IS,3R-ACPD) to assess the consequences of activating this receptor on response properties measured intracellularly in vitro or extracellularly in vivo.
