The long-term objectives of the proposed research are to understand the nature of the synaptic interactions that take place between neurons within the inner plexiform layer of the mammalian retina, and how these interactions contribute to the receptive files properties of retinal ganglion cells.
The specific aims of this project are: (1) to understand the role the neurotransmitter vasoactive intestinal peptide (VIP) plays in the formation of the receptive fields of ganglion cells; (2) to study the functional relationship of VIP-containing amacrine cells and dopaminergic amacrine cells in the rabbit retina; (3) to determine the specific sites and mechanism of action of VIP and dopamine in the retina. In initial experiments extracellular single-unit recording techniques will be used to study the physiological effects of exogenously applied VIP (and its antagonists) on the light-evoked responses of retinal ganglion cells. The isolated superfused rabbit retinal eyecup preparation will be used in these experiments since VIP, a twenty-eight amino acid peptide, does not pass the blood- retina barrier. Vasoactive intestinal peptide and related compounds will be applied to the retina by intrusion into the bathing medium via a motor-driven syringe. The results from these experiments will be compared with previously reported findings on the effects of dopamine and its agonists and antagonists on the responses of rabbit retinal ganglion cells. To explore the physiological interactions of dopamine and VIP in the retina, subsequent experiments will examine the effects of these transmitters (or related compounds) on the responses of ganglion cells when introduced together in the bathing medium. In separate but related experiments the effect of VIP, dopamine and their agonists are antagonists on the membrane potential and ionic conductance of ganglion cells and pre-ganglionic neurons will be examined using intracellular recording techniques. The main objective of these experiments is to determine the sites and mechanism of action of VIP and dopamine within the retina that may account for the observed changes in the receptive field properties of ganglion cells. In order to facilitate successful penetration of neurons with micropipettes, vital fluorescent dyes will be used in these experiments to selectively label specific subtypes of neurons in the living retina.
