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Life sciences

Endogenous ACh suppresses LTD induction and nicotine relieves the suppression via different nicotinic ACh receptor subtypes in the mouse hippocampus.


PMID 25046735

Abstract

Studying the normal role of nicotinic cholinergic systems in hippocampal synaptic plasticity is critical for understanding how cholinergic loss in Alzheimer's disease (AD) and tobacco use affect cognitive function. However, it is largely unknown how nicotinic cholinergic systems regulate the induction of long-term depression (LTD). Extracellular field potential recordings were performed in hippocampal slices prepared from wild-type, α2, α7, and β2 knockout (KO) mice. Effects of nicotine and nicotinic antagonists on LTD induction in wild-type, α2, α7, and β2 KO mice were compared. Activation of α7 nicotinic acetylcholine receptors (nAChRs) occurs during LTD-inducing stimulation to suppress LTD induction at CA3-CA1 synapses. Nicotine relieves this suppression, causing larger LTD. This nicotine effect was mediated by the activation of non-α7 nAChR subtypes, which were not activated by ACh released during LTD-inducing stimulation, and requires the presence of endogenous ACh-induced α7 nAChR activation. Furthermore, the effect of nicotine was prevented in the presence of mecamylamine, but not dihydro-β-erythroidine, and was still observed in both α2 KO and β2 KO mice. This is the first report to evaluate the involvement of different nAChR subtypes in LTD induction. Findings indicate the involvement of unique non-α7 nAChR subtypes, which have not been considered in the nicotinic modulation of hippocampal long-term potentiation, in the control of LTD induction. The implication of our results is that the loss of cholinergic projections to the hippocampus, which reduces ACh release as seen in AD patients, and nicotine from tobacco smoking can differentially affect LTD induction.