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Blockade of nicotinic acetylcholine receptors suppresses hippocampal long‐term potentiation in wild‐type but not ApoE4 targeted replacement mice
Author(s) -
Yun Sung Hwan,
Park Kyung A.,
Sullivan Patrick,
Pasternak Joseph F.,
LaDu Mary Jo,
Trommer Barbara L.
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20684
Subject(s) - long term potentiation , blockade , nicotinic agonist , hippocampal formation , acetylcholine receptor , neuroscience , acetylcholine , term (time) , receptor , pharmacology , chemistry , biology , medicine , physics , quantum mechanics
Both impaired nicotinic neurotransmission and the inheritance of apoE4 are associated with increased risk for Alzheimer disease (AD) as well as other deficiencies in memory‐related behavior. Long‐term potentiation (LTP), a cellular model of memory, is known to be altered by nicotinic agents. Recent studies also support an emergent role for apoE in LTP. We compared the effects of mecamylamine, a nonspecific antagonist of nicotinic acetylcholine receptors (nAChRs), on basal synaptic transmission and LTP in hippocampal slices from wild‐type (wt) mice and targeted replacement mice expressing human apoE4 (apoE4‐TR). Field excitatory postsynaptic potentials (EPSPs) were recorded in the dentate gyrus (DG) in response to medial perforant path activation, and theta burst stimulation was used to induce LTP. Bath application of mecamylamine (3 μM) did not alter input–output relationships or paired pulse depression in either mouse strain. Under control conditions, apoE4‐TR mice showed significantly less LTP than wt mice (17.5% ± 3.2%, n = 9, vs. 30.1% ± 3.9%, n = 11, P < 0.02). Mecamylamine reduced LTP in wt mice to a level that was similar to control levels for apoE4‐TR mice (15.7% ± 3.4%, n = 9), whereas apoE4‐TR showed no further reduction of LTP (16.6% ± 3.7%, n = 8) by mecamylamine. Thus mice expressing human apoE4 differ from wt mice both in their capacity for LTP and in the effect on LTP of nicotinic cholinergic blockade. It is possible that nicotinic neurotransmission is already compromised in apoE4‐TR mice and, hence, that interference with the integrity of this cholinergic system represents a mechanism by which inheritance of the apoE4 allele contributes to cognitive risk. © 2005 Wiley‐Liss, Inc.