Amine Neurotransmitter Regulation of Long-Term Snyaptic Plasticity in Hippocampus

摘要

The overall goal of this project was to investigate the mechanisms of long-term synaptic potentiation (LTP) at mossy fiber synapses in hippocampus, with particular emphasis on the modulation of LTP by amine neurotransmitters. During the first year of this grant, several studies were completed in which a number of hypotheses were tested for the mechanisms of LPT. We found that LTP of the mossy fiber synapses is due to an increase in the excitatory synaptic conductance with little or no change in the excitatory synaptic reversal potential, the inhibitory synaptic conductance, or the membrane properties of the postsynaptic neuron. During the first and second years, we explored the neuromodulation of LTP of LTP by norepinephrine (NE). Ne enhances the magnitude, duration, and probability of induction of LTP at mossy fiber synapses. During the second and third years, we explored the membrane actions of NE that could mediate the enhancement of LTP studies, we used a newly developed preparation of acutely exposed hippocampal neurons and patch clamp techniques. We found that NE, through beta adrenoceptors and cyclic AMP, increased the activity of single calcium channels. During the third year, we explored the neuromodulation of LTP by muscarinic cholinergic receptors. Muscarine depresses LTP a mossy fiber synapses. We have steadily progressed in our development of single cell computer models for simulating the behavior of hippocampal neurons. (aw)