Presynaptic Modulation of the Hippocampal Mossy Fiber Synapse

Abstract

Abstract : During the first year of this research project, it was demonstrated that distinct of voltage-gated calcium channels are required for the exocytosis of glutamate and types dynorphin peptides. We were also to confirm that the release of glutamate from hippocampal mossy fiber terminals is regulated by a presynaptic receptor that is sensitive to L(+)aminophosphonobutyric acid. In the second year of this research project we tested several specific hypotheses concerning presynaptic receptors and the autoregulation of the hippocampal mossy fiber synapse. Specifically, it was demonstrated that the transmitter(s) released from the mossy fiber terminals may mediate positive or negative feedback control of-the mossy fiber synaptic input, under appropriate conditions, by activating presynaptic autoreceptors. Presynaptic facilitory kainate receptors are hypothesized to enhance mossy fiber transmitter release through a mechanism that involves the activation of a guanine nucleotide-binding regulatory protein (Gs) that stimulates adenylyl cyclase and increases the activity of voltage-gated calcium channels. This presynaptic facilitation may contribute to hippocampal neurodegeneration produced by the plant-derived toxins kainate and domoate. The goal of our research during the third year has been to determine whether presynaptic inhibitory kappa opioid receptors exert an antagonistic influence on mossy fiber transmitter release that may function ot limit the overexcitation of hippocampal neurons.