Glutamate receptors play an essential role in mediating rapid excitatory synaptic activity in the vertebrate brain. It is possible that some disorders, such as epilepsy or anoxic damage, are related to changes in synaptic function, and ultimately, the properties of subsynaptic glutamate receptors. Thus, effective treatment for such disorders may come from an understanding of how the receptors are used and regulated. This information will also be needed to understand the control of signalling by rapid excitatory synapses. For example, in the auditory system, the ability to transmit rapid, ongoing, precisely timed signals is critical for conveying sensory information. Pharmacological experiments have indicated that antagonists of glutamate receptors block synaptic transmission between the large calyceal endings of the eighth cranial, or auditory, nerve fibers and postsynaptic cell bodies in the nucleus magnucellularis (NM) of the chicken, indicating that glutamate receptors mediate the response. These glutamate receptors are the focus of the proposed research. As the cells of the NM have few, if any, dendrites, and the major input for the auditory nerve is on the cell bodies, glutamate receptors on these cells must be restricted to the cell bodies. These receptors are therefore ideally situated for patch clamp studies on NM slices. Experiments are proposed to identify the subtypes of receptors, their role in the synaptic impulse and how the synaptic impulse is terminated, as well as the regulation of receptor distribution, kinetics and conductance by innervation and denervation. These experiments will be done under visual control at identified synaptic sites using video imaging techniques.
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