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Modulators of synaptic plasticity in the hippocampus Robillard, Julie


The two main forms of hippocampal synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD) represent a cellular model for learning and memory. While synaptic plasticity has been studied extensively, questions still remain on how exogenous and endogenous modulators can impact hippocampal LTP and LTD. Here, we use electrophysiology and imaging to investigate the effects of two types of modulators on synaptic plasticity. First, we look at the effects of an antagonist of the 5-HT6 re ceptor on LTP and LTD in two regions of the hippocampus, the CAl and the dentate gyrus (DG). We find that our 5-HT6 antagonist differentially affects LTP in each region and blocks hippocampal LTD. These findings are the first report of an involvement of the 5-HT6 receptor in synaptic plasticity and are particularly relevant in light of evidence showing a key role of the 5-HT6 receptor in cognition and memory. Second, we look at the effects of glutathione (GSH) supplementation on LTP in aged animals. We show that supplementing aged mice with a precursor for GSH formation reverses the mechanisms underlying hippocampal LTP from L-type calcium channel dependence back to NMDA receptor-dependence. These results suggest an important role for GSH as a modulator of synaptic plasticity in aging.

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