Role of GABAc Receptor Mediated Inhibition in Retinal Visual Function

University Of Louisville Research Foundation Inc, Louisville KY

Investigators

Abstract

The retina is a layered structure and each layer is populated by different cell classes. Most cell classes are further subdivided on the basis of their shape and on the excitatory and inhibitory inputs they receive. In the retina, as well as in the rest of the brain, inhibition plays a central role in neuronal function by modulating excitatory signals. Most inhibitory neurotransmission is mediated by the release of either glycine or gamma amino butyric acid (GABA) from the pre-synaptic cell. GABA is detected by the post-synaptic cell by one of three receptors: GABAA, GABAB or GABAC. Each GABA receptor can be identified by its structure, sensitivity to GABA and selectivity for different agonists and antagonists. These receptors also differ in their pattern of expression in the brain. These structural and functional differences lead to the hypothesis that each GABA receptor mediates a different type of inhibition in the nervous system. In the rodent retina, the GABAC receptor is located only on the axon terminals of bipolar cells. Thus, the GABAC receptor should be able to modulate the excitatory output of the bipolar cells and, thus, ultimately modulate to the overall visual response of the retina. The proposed experiments will use a mouse in which the GABAC receptor was eliminated (GABAC null mouse) via molecular genetic manipulations. The anatomy of the retina of the GABAC null mice will be examined and compared to controls to determine if the absence of the GABAC receptor alters retinal structure. The visual responses of all of the cells in the retina will be assessed in the GABAC null mice and compared to controls using a non-invasive technique, the electroretinogram. These data will determine how the absence of GABAC mediated inhibition affects the visual response at the level of the retina. These experiments represent the first attempt to define the function of an inhibitory input in the retina, using molecular genetic manipulations