Function of Ca2+-/calmodulin-dependent protein kinase IV in Ca2+-stimulated neuronal signaling and behavior

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• 作者：ZiXiang Song (1)
  Qi Chen (1)
  Qi Ding (2)
  Fei Zheng (3)
  ChengWei Li (4)
  LePing Xu (1)
  HongBing Wang (2) (5)
  
  1. Department of Adolescent Psychiatry and Behavioral Therapy ; Heping Hospital ; Changzhou ; 213003 ; China
  2. Department of Physiology ; Michigan State University ; East Lansing ; MI ; 48824 ; USA
  3. Department of Biochemistry and Molecular Biology ; Michigan State University ; East Lansing ; MI ; 48824 ; USA
  4. College of Life Science and Agronomy ; Zhoukou Normal University ; Zhoukou ; 466001 ; China
  5. Neuroscience Program ; Michigan State University ; East Lansing ; MI ; 48824 ; USA
  
• 关键词：animal behavior ; calmodulin ; CREB ; ERK1/2 ; intracellular signaling ; learning and memory
• 刊名：Science China Life Sciences
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：58
• 期：1
• 页码：6-13
• 全文大小：833 KB
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• 刊物主题：Life Sciences, general;
• 出版者：Springer Berlin Heidelberg
• ISSN：1869-1889

文摘

The activity of Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) is sensitive to activity-dependent changes in the level of intracellular Ca2+. Following neuronal stimulation, the activation of CaMKIV may trigger synaptic modifications and transcriptional responses, both of which are involved in regulating cognitive and emotional behavior. Here, we used CaMKIV knockout (KO) neurons and mice to examine the function of CaMKIV in Ca2+-stimulated intracellular signaling and animal behavior, respectively. Following NMDA receptor activation or membrane depolarization, the up-regulation of CREB (cAMP responsive element binding protein) and its target gene Bdnf (brain-derived neurotrophic factor) was intact in cortical neurons obtained from CaMKIV KO mice. CaMKIV KO mice displayed severe impairment in contextual fear memory but normal locomotor activity and anxiety level in the contextual training chamber. Although CaMKIV KO mice showed normal memory in the standard passive avoidance task, they were defective in learning the temporal dissociative passive avoidance task. As indicated by the light/dark test and marble-burying test data, CaMKIV KO mice showed less anxiety and normal perseveration. In the voluntary wheel-running test, CaMKIV KO mice showed normal running time and distance but higher maximal running speed. Our results demonstrate the function of CaMKIV in regulating different forms of fear memory, anxiety, and certain aspect of motor function.