PRESYNAPTIC RECEPTORS ON EMBRYONIC SENSORY NEURONS

电压依赖性Ca 2+通道已经进化到调节生理性 基因转录和肌肉收缩等多种过程。在 中枢神经系统，几个结构和神经系统 不同的Ca 2+通道类型共同定位于神经末梢，并且， 它们共同控制胞吐作用。由于微小的生物物理差异 在这些胞吐Ca 2+通道中， 兴奋-分泌偶联的变化， 其在神经末梢中的共同定位的基础尚不清楚。 本申请中的实验将探索以下假设： 这些通道类型由生物化学途径独特地调节 由细胞外递质激活这种差分调制 这些通道可能部分地是活动依赖性变化的基础， 突触强度，如长期抑制或增强。提出 研究将集中在两种特定的钙离子通道类型--N和P--上， 每一种都将在鸡胚感觉神经元中单独研究。 实验将I）描述控制N的调节途径 2）确定P个信道是否被类似地调制，3） 研究调节功效活性依赖性变化，和4）评估 在水平上的差异调制的生理意义 发射器释放研究结果将有助于理清复杂的网络， 影响电压依赖性Ca 2+通道的生化途径， 提供了对突触基本组织原则的深入了解， 可塑性，并最终影响到神经系统的认知过程。

Voltage-dependent Ca2+ channels have evolved to regulate physiological processes as diverse as gene transcription and muscle contraction. In the central nervous system, several structurally and pharmacologically distinct Ca2+ channel types are co-localized in nerve terminals, and, jointly, they control exocytosis. As the minor biophysical differences among these exocytotic Ca2+ channels are unlikely to provide much variation in excitation-secretion coupling, the biological rationale underlying their co-localization in nerve terminals is unclear. Experiments in this application will explore the hypothesis that each of these channel types is uniquely regulated by biochemical pathways activated by extracellular transmitters. Such differential modulation of the channels might, in part, underlie activity-dependent changes in synaptic strength, such as long-term depression or potentiation. Proposed investigations will focus on two specific Ca2+ channel types--N and P-- each to be separately studied in embryonic chick sensory neurons. Experiments will I) describe the modulatory pathways that control N channels, 2) determine whether P channels are similarly modulated, 3) study activity-dependent variation in modulatory efficacy, and 4) assess the physiological significance of differential modulation at the level of transmitter release. Results will help to sort out the complex network of biochemical pathways that impinge on voltage-dependent Ca2+ channels and offer insight into the organizing principles fundamental to synaptic plasticity and, ultimately, to cognitive processing in the nervous system.