Genetic enhancement of trace fear memory and cingulate potentiation in mice overexpressing Ca2+/calmodulin-dependent protein kinase IV.
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.
Wu
Long-Jun
LJ
Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8.
Zhang
Xue-Han
XH
Fukushima
Hotaka
H
Zhang
Fuxing
F
Wang
Hansen
H
Toyoda
Hiroki
H
Li
Bao-Ming
BM
Kida
Satoshi
S
Zhuo
Min
M
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
D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; C517685:Camk4 protein, mouse