Heterosynaptic Modulation of Long-Term Potentiation at Mossy Fiber Synapses inHippocampus

摘要

The overall goal of this research project is to investigate the cellular andmembrane mechanisms associated with the heterosynaptic modulation of long-term synaptic potentiation (LTP) at mossy fiber synapses in the hippocampus. We have previously shown that norepinephrine, through beta-adrenoceptors, enhances the magnitude, duration, and probability of induction of mossy fiber LTP, while acetylcholine, through muscarinic receptors, depresses the magnitude and probability of induction of mossy fiber LTP. The goal for the second year of this research project was to test several specific hypotheses for the induction of mossy fiber LTP. Specifically, the hypotheses relate to the possible requirement of postsynaptic calcium entry through voltage-gated calcium channels during the induction LTP. Moreover, we have been investigating the properties and distribution of voltage-gated calcium channels in hippocampal neurons and the modulation of these calcium channels by noradrenergic and cholinergic agonists. In a collaborative project with Dr. David Terrian, originally at the USAFSAM in San Antonio and now at East Carolina University, the mechanisms of neurotransmitter release from a homogeneous fraction of mossy fiber synaptosomes have been investigated. Keywords: Long-term potentiation, Noreinephrine, Acetylcholine, Synaptic plasticity, Voltage clamp, Patch clamp, Calcium channels, Hippocampus, Mossy fiber. (JES)