| Abstract No.: | A-B1023 |
| Country: | Canada |
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| Title: | GENETIC ENHANCEMENT OF TRACE FEAR MEMORY AND CINGULATE POTENTIATION IN MICE OVEREXPRESSING CA2+/CALMODULIN-DEPENDENT PROTEIN KINASE IV |
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| Authors/Affiliations: | 3 Long-Jun Wu; 3 Xue-Han Zhang; 2 Hotaka Fukushima; 3 Fuxing Zhang; 3 Hiroki Toyoda; 1 Bao-Ming Li; 2 Satoshi Kida; 3 Min Zhuo;
1 Fudan University, Tokyo, Japan; 2 Tokyo University of Agriculture, Tokyo, Japan; 3 University of Toronto, ON, Canada
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| Content: | CaMKIV is a potent mediator of Ca2+-induced gene expression associated with neuronal activity (Bito et al., 1996; Wu et al., 2001). Previous studies using CaMKIV knockout mice have revealed its critical roles in synaptic plasticity in hippocampus, cortex and amygdala as well as certain forms of memory, such as fear memory (Ho et al., 2000; Wei et al., 2002). However, previous reportes on CaMKIV functions vary significantly obtained from CaMKIV knockout mice or transgenic mice with the expression of a dominant-negative form of CaMKIV. For example, CaMKIV knockout mice show Reduced fear memory (Wei et al., 2002) but normal in spatial memory (Ho et al., 2000), while transgenic mice are normal in auditory fear conditioning but show deficits in various hippocampus-dependent tasks (Kang et al., 2001). Most recently, it has been reported that CaMKIV is important for motor memory storage (Boyden et al., 2006).
Considering that CaMKIV is highly expressed in the anterior cingulate cortex (ACC) (Wei et al., 2002), we want to address the functional role of CaMKIV in the ACC in synaptic plasticity and one of ACC-related memory, trace fear memory. By taking advantage of transgenic mice overexpressing CaMKIV, we addressed the question using integrative methods, including behavior, immunostaining and electrophysiology. Here we have found that LTP was significantly enhanced in the ACC of the mice overexpressing CaMKIV. By contrast, neither AMPA receptor mediated basal excitatory synaptic transmission nor 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. There are three novelties in the present study: (1) We are the first to use transgenic mice with CaMKIV overexpression to study the role of CaMKIV in the synaptic plasticity and behavioral memory; (2) This is the first time to show that overexpression of CaMKIV transiently enhances LTP, at both 5 min and 30 min after LTP induction; (3) This is the first time to show that overexpression of CaMKIV affects the different component of trace fear memory, such as acquisition or expression, depending on shock intensity.
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