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Behav Brain Res. 2015 Mar 15;281:69-77. doi: 10.1016/j.bbr.2014.12.018. Epub 2014 Dec 13.

TRPC3 channels critically regulate hippocampal excitability and contextual fear memory.

Author information

1
Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN, United States.
2
Department of Biotechnology and Bioengineering, Medical College of Wisconsin, Milwaukee, WI, United States.
3
Hydra Biosciences, Cambridge, MA, United States.
4
Laboratory of Neurobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
5
Department of Physiology, The University of Tennessee Health Science Center, Memphis, TN, United States.
6
Department of Pediatrics, The University of Chicago, Chicago, IL, United States.
7
Department of Biotechnology and Bioengineering, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States.
8
Department of Physiology, Northwestern Fienberg School of Medicine, Chicago, IL, United States.
9
Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN, United States. Electronic address: ckaczoro@tennessee.edu.

Abstract

Memory formation requires de novo protein synthesis, and memory disorders may result from misregulated synthesis of critical proteins that remain largely unidentified. Plasma membrane ion channels and receptors are likely candidates given their role in regulating neuron excitability, a candidate memory mechanism. Here we conduct targeted molecular monitoring and quantitation of hippocampal plasma membrane proteins from mice with intact or impaired contextual fear memory to identify putative candidates. Here we report contextual fear memory deficits correspond to increased Trpc3 gene and protein expression, and demonstrate TRPC3 regulates hippocampal neuron excitability associated with memory function. These data provide a mechanistic explanation for enhanced contextual fear memory reported herein following knockdown of TRPC3 in hippocampus. Collectively, TRPC3 modulates memory and may be a feasible target to enhance memory and treat memory disorders.

KEYWORDS:

Afterhyperpoloarization; Aging; Hippocampus; Memory; Proteomics; Transient receptor potential cation channel

PMID:
25513972
PMCID:
PMC4677051
DOI:
10.1016/j.bbr.2014.12.018
[Indexed for MEDLINE]
Free PMC Article

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