BIOCHEMICAL MECHANISMS FOR LONG TERM POTENTIATION

描述：(改编自《调查者摘要》) 通过蛋白质磷酸化进行的信号转导在 学习和记忆。在哺乳动物学习的一个重要候选机制中 和记忆，海马长时程增强(LTP)，一组不同的蛋白质 激酶在其中扮演着重要的角色。因此，cAMP依赖的蛋白激酶(PKA)， 钙/磷脂依赖激酶(PKC)，钙/钙调蛋白依赖 蛋白激酶(CaMKII)和丝裂原活化蛋白激酶(MAP)均为 是诱导LTP不同阶段所必需的。在取得巨大进步的同时 在识别LTP中涉及的激酶方面已经取得了进展，但仍存在许多空白 在我们对NMDA如何调节蛋白激酶的了解中 长时程增强过程中的受体依赖和独立过程。此外，几乎没有 了解这些激酶的下游靶标。要解决这个问题 问题，提出了三个具体目标：具体目标1，调查 LTP中Shal-型K+通道Kv4.2磷酸化的调节 特异目的2，探讨酶激活的生化机制 MAP蛋白在LTP中的作用及特异性靶点3，以探讨蛋白的作用 在LTP过程中调节CREB磷酸化的激酶。这些研究将 洞察神经元长期变化所涉及的机制 在哺乳动物中枢神经系统中的功能，并应该增加我们对 神经精神障碍的分子基础。

DESCRIPTION: (Adapted from the Investigator's Abstract) Signal transduction via protein phosphorylation plays a critical role in learning and memory. In a prominent candidate mechanism for mammalian learning and memory, hippocampal long-term potentiation (LTP), a diverse set of protein kinases plays an important role. Thus, the cAMP-dependent protein kinase (PKA), calcium/phospholipid-dependent kinase (PKC), calcium/calmodulin-dependent protein kinase (CaMKII), and mitogen-activated protein kinase (MAP kinase) all are necessary for the induction of various phases of LTP. While great progress has been made in identifying the kinases involved in LTP, there are many gaps in our knowledge of how the protein kinases are regulated by NMDA receptor-dependent and independent processes during LTP. In addition, little is understood concerning the downstream targets of these kinases. To address this question, three specific aims are proposed: Specific Aim 1, to investigate the regulation of phosphorylation of the Shal-type K+ channel Kv4.2 in LTP, Specific Aim 2, to investigate the biochemical mechanisms for the activation of MAP kinase during LTP and Specific Aim 3, to investigate the role of protein kinases in regulating CREB phosphorylation during LTP. These studies will provide insight into mechanisms involved in long-lasting changes in neuronal function in the mammalian CNS and should increase our understanding of the molecular basis of neuropsychiatric disorders.