Article

Impaired Synaptic Plasticity and cAMP Response Element-Binding Protein Activation in Ca2+/Calmodulin-Dependent Protein Kinase Type IV/Gr-Deficient Mice

Harvard University, Cambridge, Massachusetts, United States
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 10/2000; 20(17):6459-72.
Source: PubMed

ABSTRACT

The Ca(2+)/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a key effector of neuronal Ca(2+) signaling; its function was analyzed by targeted gene disruption in mice. CaMKIV/Gr-deficient mice exhibited impaired neuronal cAMP-responsive element binding protein (CREB) phosphorylation and Ca(2+)/CREB-dependent gene expression. They were also deficient in two forms of synaptic plasticity: long-term potentiation (LTP) in hippocampal CA1 neurons and a late phase of long-term depression in cerebellar Purkinje neurons. However, despite impaired LTP and CREB activation, CaMKIV/Gr-deficient mice exhibited no obvious deficits in spatial learning and memory. These results support an important role for CaMKIV/Gr in Ca(2+)-regulated neuronal gene transcription and synaptic plasticity and suggest that the contribution of other signaling pathways may spare spatial memory of CaMKIV/Gr-deficient mice.

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Available from: Talal A Chatila, Aug 15, 2015
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    • "CaMKIV is implicated in the activation of CREB during the expression of L-LTP (Bito et al., 1996; Tokuda et al., 1997). Mice lacking CaMKIV showed impairment in late phase LTP, long-term memory and CREB phosphorylation in the hippocampus (Ho et al., 2000; Kang et al., 2001). However, these mutant mice have normal early phase LTP and short-term memory. "
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    • "CaMK IV-deficient mice showed defects in a late phase of long-term depression in cerebellar Purkinje neurons[21]. CaMK IV-deficient mice also exhibit impaired neuronal CREB phosphorylation and Ca 2+ /CREB-dependent gene expression in neurons[21]. The above studies indicate that CaMK IV contributes to activating CREB and plays a critical role in the induction of LTD in the cerebellum.In our previous study, we found that subchronic exposure to As significantly down-regulated expression of the CaMK IV gene and its protein in the cerebellum of mice. "
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    • "The data reveal that, even if we were concerned with only one induction protocol variable (i.e., the number of trains), we could find a wide variability in LTP durations. A single tetanus train usually destined to produce an early phase (Huang and Kandel, 1994; Abel et al., 1997; Winder et al., 1998; Zhuo et al., 2000; Barco et al., 2002; Woo and Nguyen, 2002; Chen et al., 2003; Ahmed and Frey, 2005a; Gelinas and Nguyen, 2005; Tsokas et al., 2005; Young and Nguyen, 2005; Costa-Mattioli et al., 2007; Ris et al., 2009) produces different durations extending from less than to approximately 1 h (Huang and Kandel, 1994, 1996; Qi et al., 1996; Abel et al., 1997; Winder et al., 1998; Ho et al., 2000; Zhuo et al., 2000; Matsushita et al., 2001; Miller et al., 2002; Woo and Nguyen, 2002; Alarcon et al., 2004; Barco et al., 2005; Huang et al., 2005; Meng et al., 2005; Tsokas et al., 2005; Young and Nguyen, 2005; Antion et al., 2008), approximately 2 h (Barad et al., 1998; Barco et al., 2002; Chen et al., 2003; Banko et al., 2005; Gelinas and Nguyen, 2005; Costa-Mattioli et al., 2007), 3 h (Reymann et al., 1985; Ahmed and Frey, 2005a; Ris et al., 2009), or 4 h (Cai et al., 2010). "
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