In this revised application, the applicant has extensively rewritten the proposal (over 85 percent of the content has been changed). The applicant plans to focus his effort on the ligand- and voltage-gated channels in one population of retinal neurons, the starburst amacrine cells. He will use the whole cell voltage clamp technique to record starburst amacrine cells labeled with DAP1. There are three specific aims in this application. The applicant plans to study: (1) the physiological and pharmacological properties of major synaptic receptors and voltage-gated channels in starburst amacrine cells with a view toward examining the functional roles of these channels in shaping postsynaptic responses and action potentials in starburst amacrine cells: for ligand-gated receptors, the desensitization rate and the relative contribution of NMDA and nonNMDA receptors, and the presence of nicotinic Ach and APB receptors in starburst amacrine cells will be investigated whereas for voltage-gated channels, the channel kinetics, voltage-dependence, and pharmacology of Ca2+, K+, and Na+ channels will be studied; (2) the distribution of voltage- and ligand-gated conductances in soma and dendrites, so that he can determine whether there is any asymmetry of distribution and functional polarization in starburst amacrine cells; and (3) whether ligand- and voltage-gated conductances in starburst amacrine cells can be modulated by modulators such as adenosine, GABA-A agonists, muscarinic agonists, dopamine and neuropeptides. The applicant seeks to determine which modulatory agents are important to regulate starburst amacrine response and outputs to retinal ganglion cells.
Showing the most recent 10 out of 13 publications
