MODULATION OF SYNAPTIC TRANSMISSION

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The detection and signaling of visual information in retina requires the establishment and maintenance of millions of individual synapses. Not only must these synaptic circuits reliably and rapidly transmit the light-evoked signals generated in rods and cones, they must be modifiable as lighting conditions change during the day. Excitatory signals in the retina, and the brain, are transmitted via synapses that use glutamate as their neurotransmitter. Because glutamate does not cross the brain/blood barrier, glutamate has to be synthesized in the nervous system. A glutamate/glutamate recycling system replenishes synaptic glutamate. In retina, little is known about how glutamine is transported out of the Mtiller glial cells and back into the glutamatergic neurons for re-synthesis of glutamate. A principal aim of proposed research centers on identifying and characterizing the glutamine transport mechanisms in retina. Recently it has been discovered that glial cells are not passive elements compared to neurons but they release neurotransmitters that regulate synaptic transmission between neurons. A second aim of this research is to identify and characterize the mechanism(s) by which glutamate is released from Muller glia cells in retina. Elucidating these mechanisms in the retina, a more experimentally tractable region of the nervous system, will serve as a model for glutamate regulation in the CNS. Glutamate-induced excitotoxicity underlies many of the changes produced by pathological conditions such as ischemia and glaucoma. Neurotrophins regulate development and maintain synaptic activity. Examination of mice lacking the neurotrophin receptor TrkB show decreased synaptic transmission from rod photoreceptors. To eliminate deleterious effects that TrkB deletions have on other somatic functions Louis Reichardt will use retina-specific promoters to delete TrkB receptors in the eye only. A third major goal is to characterize the effects of these deletions on light-evoked responses in retina.