Regulation of axonal and synaptic signaling in interneurons

摘要 神经元编码各种各样的信号，每个信号都与翻译感觉反应或 将记忆转化为行为。如何优化细胞和突触以满足这些需求？我们的工作已用于 体外模型系统在树突、轴突初始水平上理解这种功能的特化 节段和神经末梢。该实验室的研究延伸了神经元功能的经典观点， 通过展示轴突起始段和神经末梢中的神经递质受体如何 改变轴突和突触通讯的独特角色。在这项提案中，我们将从新的角度来看待 轴突的作用。除了它在尖峰信号单向传输中的功能外，我们还将研究亚阈值是如何 在胞体、轴突或终末产生的信号沿轴突向前和向后扩散 修改钉状物及其传播的说明。此外，我们将研究钙是如何释放的 调节新生儿脑内兴奋的机制。实现这些目标的关键将是使用精心挑选的 小鼠品系的特点是用荧光团对神经元进行稀疏的荧光标记，清楚地揭示了 活体脑片中神经元的隔间，从树突到神经末梢。这项研究应该会揭示 与动作电位平行工作的信号的新维度，特别是在 神经微电路

Summary Neurons encode a wide variety of signals, each with specific relevance for translating a sensory response or memory into behavior. How are cells and synapses optimized to meet these needs? Our work has used in vitro model systems to understand such specializations of function at the level of the dendrite, the axon initial segment and the nerve terminal. The lab's studies have stretched the classical views of neuronal function, for example by showing how neurotransmitter receptors in the axon initial segment and in the nerve terminal have unique roles for modifying axon and synaptic communication. In this proposal, we will turn to a new view of the role of the axon. Beyond its function in the one-way transmission of spikes, we will examine how subthreshold signals generated in the soma, the axon or the terminal spread along the axon in the forward and reverse directions to modify the spike and its propagation. Additionally, we will examine how calcium release mechanism modulate excitation in neonatal brain. Key to these aims will be the use of carefully selected mouse lines that feature sparse fluorescent labeling of neurons with fluorophores that clearly reveal each compartment of the neuron in living brain slices, from dendrite to nerve terminal. The research should reveal new dimensions of signaling that operate in parallel with the action potential, particularly in interneurons in neural microcircuits