title: The role of calsenilin/DREAM/KChIP3 in contextual fear conditioning.
abstract: Potassium channel interacting proteins (KChIPs) are members of a family of calcium binding proteins that interact with Kv4 potassium (K(+)) channel primary subunits and also act as transcription factors. The Kv4 subunit is a primary K(+) channel pore-forming subunit, which contributes to the somatic and dendritic A-type currents throughout the nervous system. These A-type currents play a key role in the regulation of neuronal excitability and dendritic processing of incoming synaptic information. KChIP3 is also known as calsenilin and as the transcription factor, downstream regulatory element antagonist modulator (DREAM), which regulates a number of genes including prodynorphin. KChIP3 and Kv4 primary channel subunits are highly expressed in hippocampus, an area of the brain important for learning and memory. Through its various functions, KChIP3 may play a role in the regulation of synaptic plasticity and learning and memory. We evaluated the role of KChIP3 in a hippocampus-dependent memory task, contextual fear conditioning. Male KChIP3 knockout (KO) mice showed significantly enhanced memory 24 hours after training as measured by percent freezing. In addition, we found that membrane association and interaction with Kv4.2 of KChIP3 protein was significantly decreased and nuclear KChIP3 expression was increased six hours after the fear conditioning training paradigm with no significant change in KChIP3 mRNA. In addition, prodynorphin mRNA expression was significantly decreased six hours after fear conditioning training in wild-type (WT) but not in KO animals. These data suggest a role for regulation of gene expression by KChIP3/DREAM/calsenilin in consolidation of contextual fear conditioning memories.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Jon C
authors.initials: JC
authors.lastname: Alexander
authors.forename: Carmel M
authors.initials: CM
authors.lastname: McDermott
authors.forename: Tumay
authors.initials: T
authors.lastname: Tunur
authors.forename: Vicky
authors.initials: V
authors.lastname: Rands
authors.forename: Claire
authors.initials: C
authors.lastname: Stelly
authors.forename: Debra
authors.initials: D
authors.lastname: Karhson
authors.forename: Mark R
authors.initials: MR
authors.lastname: Bowlby
authors.forename: W Frank
authors.initials: WF
authors.lastname: An
authors.forename: J David
authors.initials: JD
authors.lastname: Sweatt
authors.forename: Laura A
authors.initials: LA
authors.lastname: Schrader
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002466:Cell Nucleolus / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology*; D003463:Cues; D004745:Enkephalins / Q000235:genetics; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism; D047468:Immunoprecipitation / Q000379:methods; D051605:Kv Channel-Interacting Proteins / Q000172:deficiency / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D045442:Rotarod Performance Test; D012684:Sensory Thresholds / Q000502:physiology; D051672:Shal Potassium Channels / Q000378:metabolism; D013997:Time Factors
chemical_list: C496756:Csen protein, mouse; D004745:Enkephalins; D051605:Kv Channel-Interacting Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D012097:Repressor Proteins; D051672:Shal Potassium Channels; C033660:preproenkephalin