CALCIUM SENSITIVE ADENYLYL CYCLASES AND NEUROPLASTICITY

描述：Ca 2 +/钙调蛋白敏感的腺苷酸环化酶（AC）可能是 对各种突触可塑性都很重要。 转基因 缺乏1型腺苷酸环化酶（I-AC）的小鼠缺乏 空间学习的几种方式。 生化分析这些 老鼠的大脑中可能含有至少一个 Ca ~（2+）/钙调素敏感型AC。 本提案的长期目标 确定是否需要Ca 2 +/钙调素依赖性AC， LTP或空间学习，决定哪些基因在培养的初级 神经元受cAMP调节，并确定Ca 2 +/钙调素- 敏感的AC有助于Ca 2+调节基因表达， 培养的神经元 IX-AC对CaM和Ca ~（2+）的敏感性也将随着IX-AC浓度的增加而增加。 追究 该项目的具体目标包括： 确定I-AC、III-AC和VIII-AC用于特定用途的必要性 LTP或LTD的形式，并确定是否Ca 2 +/CaM的敏感性， I-AC对于LTP和/或空间学习至关重要。 而且 研究者建议分离IX-AC克隆，确定AC是否 神经元的活动受膜电位调节，确定 培养的海马神经元中哪些基因受cAMP调控， 确定哪种形式的LTP激活CRE介导的转录，以及 确定Ca 2 +/钙调素敏感性AC是否有助于调节 基因在培养的神经元中的表达。

DESCRIPTION: Ca2+/calmodulin-sensitive adenylyl cyclases (AC) are likely to be important for various types of synaptic plasticity. Transgenic mice deficient for type 1 adenylyl cyclase (I-AC) are deficient in certain types of spatial learning. Biochemical analysis of these mice indicate that the brain may contain at least one other Ca2+/calmodulin-sensitive AC. The long-term goals of this proposal are to determine if Ca2+/calmodulin-dependent ACs are required for LTP or spatial learning, determine which genes are in cultured primary neurons are regulated by cAMP, and determine if the Ca2+/calmodulin- sensitive ACs contribute to Ca2+ regulation of gene expression in cultured neurons. The sensitivity of IX-AC to CaM and Ca2+ will also be investigated. The specific aims of this project include the determination of the necessity of I-AC, III-AC and VIII-AC for specific forms of LTP or LTD and determining if the Ca2+/CaM sensitivity of I-AC is crucial for LTP and/or spatial learning. Furthermore, the investigator proposes to isolate the clone for IX-AC, determine if AC activity in neurons is regulated by membrane potential, determine what genes in cultured hippocampal neurons are regulated by cAMP, determine which forms of LTP activate CRE-mediated transcription, and determine if Ca2+/calmodulin-sensitive ACs contribute to regulation of gene expression in cultured neurons.