title: Genetic enhancement of trace fear memory and cingulate potentiation in mice overexpressing Ca2+/calmodulin-dependent protein kinase IV.
abstract: Long-term potentiation (LTP) is a key cellular model for studying mechanisms for learning and memory. Previous studies reported that the Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) is critical for gene regulation, and behavioral learning and memory. Less is known about the roles of CaMKIV in cortical plasticity and trace fear memory. Here we have found that LTP was significantly enhanced in the anterior cingulate cortex (ACC) of the mice overexpressing CaMKIV. By contrast, neither alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated basal excitatory synaptic transmission nor N-methyl-d-aspartate (NMDA) receptor-mediated excitatory postsynaptic currents were affected. Furthermore, paired-pulse ratio in the transgenic mice is normal. In behavioral tests, we found that the CaMKIV transgenic mice exhibited significant enhancement in trace fear memory, while the acute sensory thresholds were not affected. Our results provide strong evidence that forebrain CaMKIV contributes to trace fear memory by enhancing synaptic potentiation in the ACC.
authors.affiliation: Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Long-Jun
authors.initials: LJ
authors.lastname: Wu
authors.forename: Xue-Han
authors.initials: XH
authors.lastname: Zhang
authors.forename: Hotaka
authors.initials: H
authors.lastname: Fukushima
authors.forename: Fuxing
authors.initials: F
authors.lastname: Zhang
authors.forename: Hansen
authors.initials: H
authors.lastname: Wang
authors.forename: Hiroki
authors.initials: H
authors.lastname: Toyoda
authors.forename: Bao-Ming
authors.initials: BM
authors.lastname: Li
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kida
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4 / Q000096:biosynthesis* / Q000235:genetics; D002540:Cerebral Cortex / Q000502:physiology*; D003214:Conditioning, Classical; D005239:Fear / Q000502:physiology*; D024861:Genetic Enhancement; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; C517685:Camk4 protein, mouse