ELECTROPHYSIOLOGY OF PRESYNAPTIC NERVE TERMINALS

神经生物学中的一个基本问题是突触前神经元的兴奋性。 神经末梢，这是关键的突触释放 神经传递素 调节末梢兴奋性的因素有 不太了解。 这是由于脊椎动物的体积非常小 神经末梢，这使得细胞内记录不可能， 获得。 似乎许多经典和肽类神经递质，如 以及一氧化氮和一氧化碳，可以影响电 突触前末梢的性质。 然而，现有的证据表明， 这种影响在很大程度上是间接的，依赖于突触后神经元的变化。 对释放的发射器的响应。 在本提案中，将使用一个独特的模型系统来研究 脊椎动物神经末梢的电特性。 副交感 鸡纤毛含有“巨大的”突触前神经末梢，形成杯状结构， 睫状神经元上的类似或杯状末梢。 我们取得了 从这些神经末梢的细胞内记录， 对于一些离子通道和神经递质受体， terminals.将讨论以下基本问题， 离子通道存在于脊椎动物的神经末梢上， 它们在调节末端区域的膜电位中起作用？ 突触前神经递质受体如何改变 神经末梢？位于突触前的神经递质受体 神经末梢在功能上耦合到不同的离子通道， 相同的受体是否位于同一神经元的索马和树突上？ 将进行细胞内（夏普）和全细胞膜片钳记录 离体完整睫状神经节的杯状终末。 使用 脑切片制备，类似的记录将从神经元中进行， 鸡外侧Edinger-Westphal核，由于大终末在 睫状神经节起源于该末端细胞体 受体和类似的体细胞/树突状受体对同一类 神经元 阿片类药物和速激肽都将用于这些研究， 因为这两类神经肽的受体都存在于艾丁格上， Westphal胞体和萼状终端。特别感兴趣的是阿尔穆 和δ阿片受体，因为我们的初步结果表明，这些 受体与末端区域的不同离子通道偶联 而不是躯体区域。 产生这些不同的机制 将使用具有抑制作用的各种试剂来检查反应。 或对G蛋白介导的细胞内途径的刺激作用。 这项建议旨在获得有关因素的新信息， 改变突触前神经末梢的兴奋性。 模型系统 提供了一个独特的机会，以解决几个基本的 神经生物学中的问题，直接关系到功能， 位于整个神经系统的突触前神经末梢。 正常突触前末梢兴奋性的改变可能存在 在许多神经系统疾病中，包括癫痫和阿尔茨海默氏症 疾病

A fundamental problem in neurobiology is the excitability of presynaptic nerve terminals, which is critical for synaptic release of neurotransmitter. The factors regulating excitability of terminals are poorly understood. This is due to the extremely small size of vertebrate nerve terminals, which make intracellular recordings impossible to obtain. It appears that many classical and peptide neurotransmitter, as well as nitric oxide and carbon monoxide, can influence the electrical properties of presynaptic terminals. However, the existing evidence for such influence is largely indirect, relying on changes in postsynaptic responses to released transmitter. In this proposal, a unique model system will be used to study the electrical properties of vertebrate nerve terminals. The parasympathetic chick ciliary contains "giant" presynaptic nerve terminal that form cup- like or calyciform endings on ciliary neurons. We have made intracellular recordings from these nerve terminals, and find evidence for a number of ion channels and neurotransmitter receptors on the terminals. The following fundamental questions will be addressed, Which ion channels are present on vertebrate nerve terminals, and what role do they play in regulating the membrane potential of the terminal region? How do presynaptic neurotransmitter receptors alter the excitability of nerve terminal? Can neurotransmitter receptors located on presynaptic nerve terminals be functionally coupled to different ion channels than are identical receptors situated on the same neuron's soma and dendrites? Intracellular (sharp) and whole-cell patch clamp recording will be made from calyciform terminals in intact ciliary ganglia in vitro. Using a brain slice preparation, similar recordings will be made from neurons in the chick lateral Edinger-Westphal nucleus, since the large terminal in the ciliary ganglion originate from cell bodies in this terminal receptors and similar somatic/dendritic receptors on the same class of neurons. Both opioids and tachykinins will be used for these studies, as receptors for both classes of neuropeptides are present on Edinger- Westphal somas and on calyciform terminals. OF particular interest ar mu and delta opioid receptors, since our initial results indicate that these receptors are coupled to different ion channels in the terminal region than in the somatic region. The mechanisms producing these disparate responses will be examined using a variety of agents that have inhibitory or stimulatory effects on G-protein-mediated intracellular pathways. This proposal seeks to obtain new information regarding factors that can alter the excitability of presynaptic nerve terminal. The model system to be used provides a unique opportunity to address several fundamental questions in neurobiology that are directly relevant to the function of presynaptic nerve terminals located throughout the nervous system. Alterations in normal presynaptic terminal excitability may be present in a number of neurological disease, including epilepsy and Alzheimer's disease.