Amine Neurotransmitter Regulation of Long-Term Synaptic Plasticity in Hippocampus.

The overall goal of the research project is to investigate the mechanisms of long-term synaptic potentiation LTP in hippocampus, with particular emphasis on the modulation of LTP by amine neurotransmitters. During the first year of the grant, it was shown that LTP of the mossy fiber synapse in hippocampus is associated with an increase in the excitatory synaptic conductance with no change in reversal potential or membrane properties of the postsynaptic neuron. It was also shown that no long-term change in the inhibitory synaptic conductance was associated with LTP at the mossy fibers. In other work, various hypotheses associated with the previously observed modulation of LTP by norepinephrine NE were tested. It was found that cyclic AMP could mimic the action of NE and that NE could enhance LTP in the absence of synaptic inhibition. The cellular effects of NE were explored in an isolated hippocampal neuron system in which patch-clamp techniques were utilized. It was found that NE produced an enhancement in the voltage-dependent calcium current. Progress also was made towards the development of a computer model that simulates the behavior of single hippocampal neurons.