CALCIUM SENSITIVE ADENYLYL CYCLASES AND NEUROPLASTICITY

描述：对钙离子/钙调素敏感的腺酰环化酶(AC)可能是 对各种类型的突触可塑性都很重要。转基因 缺乏1型腺酰环化酶(I-AC)的小鼠 某些类型的空间学习。这些物质的生化分析 老鼠表明，大脑可能至少包含一个其他的 钙/钙调蛋白敏感性AC。这项提议的长期目标是 是为了确定是否需要依赖钙/钙调蛋白的急性冠脉综合征 LTP或空间学习，确定培养的原代细胞中有哪些基因 神经元受cAMP的调节，并决定是否钙/钙调蛋白- 敏感的急性冠脉综合征参与钙离子对心肌细胞基因表达的调节 培养的神经元。IX-AC对CaM和Ca~(2+)的敏感性也 被调查。这项计划的具体目标包括 I-AC、III-AC和VIII-AC用于特定用途的必要性的确定 LTP或LTD的形式及其钙/钙敏感性的测定 I-AC对LTP和/或空间学习至关重要。此外， 研究人员建议分离IX-AC的克隆，确定AC 神经元的活动受膜电位的调节，确定 培养的海马神经元中哪些基因受cAMP调控， 确定哪些形式的LTP激活Cre介导的转录，以及 确定钙/钙调蛋白敏感型ACS是否参与调节 培养神经元的基因表达。

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.