title: TRPC3 channels critically regulate hippocampal excitability and contextual fear memory.
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.
authors.affiliation: Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN, United States.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Neuner
authors.affiliation: Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN, United States.
authors.forename: Lynda A
authors.initials: LA
authors.lastname: Wilmott
authors.affiliation: Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN, United States.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Hope
authors.affiliation: Department of Biotechnology and Bioengineering, Medical College of Wisconsin, Milwaukee, WI, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Hoffmann
authors.affiliation: Hydra Biosciences, Cambridge, MA, United States.
authors.forename: Jayhong A
authors.initials: JA
authors.lastname: Chong
authors.affiliation: Laboratory of Neurobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
authors.forename: Joel
authors.initials: J
authors.lastname: Abramowitz
authors.affiliation: Laboratory of Neurobiology, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.affiliation: Department of Physiology, The University of Tennessee Health Science Center, Memphis, TN, United States.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: O'Connell
authors.affiliation: Department of Pediatrics, The University of Chicago, Chicago, IL, United States.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Tryba
authors.affiliation: Department of Biotechnology and Bioengineering, Medical College of Wisconsin, Milwaukee, WI, United States; Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greene
authors.affiliation: Department of Physiology, Northwestern Fienberg School of Medicine, Chicago, IL, United States.
authors.forename: C
authors.initials: C
authors.lastname: Savio Chan
authors.affiliation: Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center, Memphis, TN, United States. Electronic address: ckaczoro@tennessee.edu.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Kaczorowski
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000523:psychology*; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D050052:TRPC Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D050052:TRPC Cation Channels; C104603:TRPC3 cation channel
keywords: Afterhyperpoloarization; Aging; Hippocampus; Memory; Proteomics; Transient receptor potential cation channel