The control of the strength of individual synapses is essential to fine- tuning the performance of neural circuits. Synaptic strength may be regulated in the short term by trains of high frequency pre-synaptic action potential which at many synapses leads to short-term synaptic depression. Using the large calyceal synapses of the chick cochlear nucleus (nucleus magnocellularis, or nMAG), we will carry out experiments which are based upon the following hypothesis: We propose that there are multiple forms of short-term depression, each with distinctive properties, and that these become recruited at specific frequencies of neural activity. By the independent regulation of these forms of depression, neurons may produce changes in synaptic strength at specific ranges of frequencies and not at others. This concept, which we term complex depression, would provide a powerful and sophisticated means for control of neural circuits, and will be comprehensively tested in the proposed studies. These will employ patch clamp recordings and the direct measurement of pre- and postsynaptic signals during the course of depression, testing specific hypotheses about the types, origins and function of depression. Specifically, we will first document that there are different components to depression and how each contributes to the control of synaptic strength at specific frequencies of synaptic activity. Then, we will identify the probable cellular mechanisms that underlie different forms of depression. Moreover, we will examine how depression can be regulated by transmitter uptake systems and by patterns of activity. Finally, we will determine the functional consequences of depression when synapses converse onto a single target cell. The results of the analyses will give new insight into the factors that determine the optical transmission of signals in the brain, and will contribute to an understanding of sensory or cognitive deficits.
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