The overall goal of this program is to better understand visual information processing in the mammalian inner retina by defining and characterizing its transmitter systems, cell morphology and microcircuitry. The focus of these studies is on GABA, a prominent inhibitory transmitter that is expressed in a high percentage of amacrine cells, and on neuroactive peptides that are expressed in subpopulations of amacrine cells and co-occur with GABA Emphasis will be placed on characterizing the bipolar and amacrine cell types that these transmitters act upon by determining the distribution and cellular localization of their receptors. These studies will also identity the cells that contain GABA plasma membrane transporters to define the sites of GABA uptake and inactivation at the cellular level. The following are the specific aims of this proposal.
Specific aim 1 will identity the GABA-A receptor subunits and determine their distribution and cellular localization to elucidate the sites of action of GABA-containing amacrine and interplexiform cells.
Specific aim 2 will define the expression and cellular localization of tachykinin (TK) and vasoactive intestinal polypeptide (VIP) receptor mRNAs to elucidate the sites of action of TK peptides and VIP, which are located in morphologically distinct amacrine cell populations and co-expressed with GABA.
Specific aim 3 will identity the expression and cellular localization of the GABA plasma membrane transporters to elucidate the cellular sites of GABA uptake and inactivation These experiments will utilize sequence specific oligonucleotide and RNA probes, and specific antibodies to the GABA-A receptor subunits, TK and VIP receptors, and GABA transporters to accomplish the experimental objectives of this application Proposed studies will utilize both in situ hybridization and immunohistochemistry with rat and rabbit retinal model systems. These studies will provide important insights for an understanding of the role of a major inhibitory transmitter, GABA, and of neuroactive peptides that act as modulatory substances in the inner plexiform layer. These studies will thus provide the basis for a better understanding of visual information processing in the retina. These objectives are consistent with the health related goals of the National Eye Institute to develop more effective treatments and ultimately to prevent retinal diseases by defining the neurochemical and structural organization of the retina.
Showing the most recent 10 out of 82 publications
