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Blockade of nicotinic acetylcholine receptors suppresses hippocampal long-term potentiation in wild-type but not ApoE4 targeted replacement mice.

Publication ,  Journal Article
Yun, SH; Park, KA; Sullivan, P; Pasternak, JF; Ladu, MJ; Trommer, BL
Published in: J Neurosci Res
December 15, 2005

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 microM) 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.

Duke Scholars

Published In

J Neurosci Res

DOI

ISSN

0360-4012

Publication Date

December 15, 2005

Volume

82

Issue

6

Start / End Page

771 / 777

Location

United States

Related Subject Headings

  • Time Factors
  • Synaptic Transmission
  • Receptors, Nicotinic
  • Nicotinic Antagonists
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice
  • Mecamylamine
  • Male
  • Long-Term Potentiation
 

Citation

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Yun, S. H., Park, K. A., Sullivan, P., Pasternak, J. F., Ladu, M. J., & Trommer, B. L. (2005). Blockade of nicotinic acetylcholine receptors suppresses hippocampal long-term potentiation in wild-type but not ApoE4 targeted replacement mice. J Neurosci Res, 82(6), 771–777. https://doi.org/10.1002/jnr.20684
Yun, Sung Hwan, Kyung A. Park, Patrick Sullivan, Joseph F. Pasternak, Mary Jo Ladu, and Barbara L. Trommer. “Blockade of nicotinic acetylcholine receptors suppresses hippocampal long-term potentiation in wild-type but not ApoE4 targeted replacement mice.J Neurosci Res 82, no. 6 (December 15, 2005): 771–77. https://doi.org/10.1002/jnr.20684.
Yun SH, Park KA, Sullivan P, Pasternak JF, Ladu MJ, Trommer BL. Blockade of nicotinic acetylcholine receptors suppresses hippocampal long-term potentiation in wild-type but not ApoE4 targeted replacement mice. J Neurosci Res. 2005 Dec 15;82(6):771–7.
Yun, Sung Hwan, et al. “Blockade of nicotinic acetylcholine receptors suppresses hippocampal long-term potentiation in wild-type but not ApoE4 targeted replacement mice.J Neurosci Res, vol. 82, no. 6, Dec. 2005, pp. 771–77. Pubmed, doi:10.1002/jnr.20684.
Yun SH, Park KA, Sullivan P, Pasternak JF, Ladu MJ, Trommer BL. Blockade of nicotinic acetylcholine receptors suppresses hippocampal long-term potentiation in wild-type but not ApoE4 targeted replacement mice. J Neurosci Res. 2005 Dec 15;82(6):771–777.
Journal cover image

Published In

J Neurosci Res

DOI

ISSN

0360-4012

Publication Date

December 15, 2005

Volume

82

Issue

6

Start / End Page

771 / 777

Location

United States

Related Subject Headings

  • Time Factors
  • Synaptic Transmission
  • Receptors, Nicotinic
  • Nicotinic Antagonists
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice
  • Mecamylamine
  • Male
  • Long-Term Potentiation