Genetic enhancement of trace fear memory and cingulate potentiation in mice overexpressing Ca2+/calmodulin-dependent protein kinase IV

Long Jun Wu, Xue Han Zhang, Hotaka Fukushima, Fuxing Zhang, Hansen Wang, Hiroki Toyoda, Bao Ming Li, Satoshi Kida, Min Zhuo

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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 α-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.

Original languageEnglish (US)
Pages (from-to)1923-1932
Number of pages10
JournalEuropean Journal of Neuroscience
Issue number8
StatePublished - Apr 2008


  • Anterior cingulate cortex
  • CaMKIV
  • Long-term potentiation
  • Trace fear memory

ASJC Scopus subject areas

  • Neuroscience(all)


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