Regulation of Intrinsic Plasticity by CaMKII

CaMKII 对内在可塑性的调节

• 批准号: 6745573
• 负责人: Leslie C Griffith
• 金额: $ 28.83万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-05 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6745573
• 关键词: Drosophilidae; biological signal transduction; calcium flux; calmodulin dependent protein kinase; electrophysiology; enzyme activity; enzyme mechanism; green fluorescent proteins; membrane potentials; motor neurons; neural conduction; neural plasticity; neurogenetics; neuromuscular junction; neuronal transport; neuropharmacology; potassium channel; transfection

DESCRIPTION (provided by applicant): CaMKII plays an important role in learning and memory formation in Drosophila as well as in other animals. We have recently found that CaMKII alters the excitability of identified neurons in the third instar larval nervous system of Drosophila. We will study the mechanisms of this modulation and explore its possible role in neuronal plasticity. Genetic access to these identified neurons will allow mechanistic studies of intrinsic property modulation that have not been possible in other systems. Our specific aims are: 1) Determine the effects of genetic and pharmacological manipulation of CaMKII on the excitability and behavior of central neurons. We will look at the effects of CaMKII on firing properties such as threshold, spike amplitude, spike waveform and firing frequency. We will define the voltage-dependent currents that are modulated by short-term and long-term alteration of kinase activity. 2) Determine the cellular mechanisms of activity-dependent modulation of intrinsic properties. We have shown that activity can induce a long-lasting increase in neuronal excitability in Drosophila motor neurons. We will investigate this phenomenon to determine the roles of firing pattern, calcium influx and activity of the postsynaptic cell in induction. We will determine if activity can change the response of the neuron to its normal presynaptic partners. 3) Determine the signal transduction mechanisms of activity-dependent modulation of intrinsic properties. We will define the conductances that are modulated by this process and investigate the role of CaMKII using transgenes and drugs. These studies will provide insight into a fundamental mechanism of plasticity and define novel roles for CaMKII in the regulation of short-term and long-term changes in excitability. Understanding these pathways will advance our knowledge of the basic processes that shape behavior.

描述（由申请人提供）：Camkii在果蝇和其他动物的学习和记忆形成中起着重要作用。我们最近发现，CaMKII改变了果蝇第三龄幼虫神经系统中鉴定的神经元的兴奋性。我们将研究此调节的机制，并探索其在神经元可塑性中的可能作用。遗传访问这些已鉴定的神经元将允许在其他系统中无法进行内在性质调制的机械研究。 我们的具体目的是：1）确定CAMKII遗传和药理学操纵对中央神经元的兴奋性和行为的影响。我们将研究CAMKII对阈值，尖峰振幅，尖峰波形和发射频率等发射特性的影响。我们将定义由短期和长期变化激酶活性调节的电压依赖性电流。 2）确定固有特性的活性依赖性调节的细胞机制。我们已经表明，活性会引起果蝇运动神经元中神经元兴奋性的长期增加。我们将研究这种现象，以确定发射模式，钙涌入和突触后细胞在诱导中的作用。我们将确定活动是否可以改变神经元对正常突触前伴侣的反应。 3）确定固有特性的活性依赖性调制的信号转导机制。我们将定义该过程调节的电导，并使用转基因和药物研究CAMKII的作用。这些研究将洞悉可塑性的基本机制，并确定CAMKII在调节兴奋性短期和长期变化中的新作用。了解这些途径将促进我们对塑造行为的基本过程的了解。