Muscarinic L.T.D. Modulation by Cholinergic Denervation

University Of Alabama At Birmingham, Birmingham AL

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Abstract

[unreadable] DESCRIPTION (provided by applicant): [unreadable] I have previously characterized a form of long term depression in acute rat hippocampal slices induced by activation of M1 muscarinic acetylcholine receptors (muscarinic LTD; mLTD). Destruction of cholinergic innervation of the hippocampus, such as what occurs in Alzheimer's Disease, results in loss of mLTD but an endogenous compensatory mechanism exists in the nervous system to prevent loss of mLTD. In response to destruction of hippocampal cholinergic input, peripheral sympathetic fibers originating at the superior cervical ganglion sprout and innervate the cholinergic denervated fields. This phenomenon, termed hippocampal sympathetic ingrowth (HSl) has been observed in humans with Alzheimer's Disease. In slices from animals with hippocampal cholinergic denervation and HSI, mLTD is expressed as in control slices. This proposal will study the mechanism by which HSI, an adrenergic compensatory mechanism, can maintain mLTD in the absence of hippocampal cholinergic innervation. [unreadable] [unreadable]