Blockade of nicotinic acetylcholine receptors suppresses hippocampal long‐term potentiation in wild‐type but not ApoE4 targeted replacement mice
- 4 November 2005
- journal article
- research article
- Published by Wiley in Journal of Neuroscience Research
- Vol. 82 (6), 771-777
- https://doi.org/10.1002/jnr.20684
Abstract
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.Keywords
This publication has 57 references indexed in Scilit:
- Novel modulatory mechanisms revealed by the sustained application of nicotine in the guinea‐pig hippocampus in vitroThe Journal of Physiology, 2003
- Reelin and ApoE Receptors Cooperate to Enhance Hippocampal Synaptic Plasticity and LearningPublished by Elsevier BV ,2002
- Differential Effects of PACAP-38 on Synaptic Responses in Rat Hippocampal CA1 RegionLearning & Memory, 2001
- AMPA receptor regulation and LTP in the hippocampus of young and aged apolipoprotein E-deficient miceNeurobiology of Aging, 2001
- Expression of nicotinic acetylcholine receptors in Alzheimer’s disease: postmortem investigations and experimental approachesBehavioural Brain Research, 2000
- Hippocampal synaptic transmission enhanced by low concentrations of nicotineNature, 1996
- Chronic nicotine reverses working memory deficits caused by lesions of the fimbria or medial basalocortical projectionCognitive Brain Research, 1993
- Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset FamiliesScience, 1993
- The Cholinergic Hypothesis of Geriatric Memory DysfunctionScience, 1982
- Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal ForebrainScience, 1982