POSTSYNAPTIC FACTORS AFFECTING SYNAPTIC EFFICACY

我们的长期目标是确定 中枢突触和神经回路的运作。 我们 特别感兴趣的是阐明 突触后膜影响疗效和时程 也可能提供了 神经元可塑性。 显著的突触后特性 包括递质-受体相互作用的参数， 为制定合理的药物治疗方案提供依据， 和结构参数。 后者包括受体或 结合位点密度，受体的突触下位置， 突触接触区的大小和定位 来自相同或不同来源的估算。 另一个重要 因素是存在或avsece的发射失活 影响相邻突触的程度的机制 建议的研究旨在研究中央 抑制性（甘氨酸能）和兴奋性（可能是代谢性）： 一种脊椎动物神经元上的突触， 细胞，并开发量子响应的计算机模型。 大部分的工作都是基于这样一个概念，即非线性相互作用 在相邻突触之间，可能是由于 发射机从一个联系人到下一个，在某些情况下， 受体性质的变构调节。 特别针对 包括研究1）相邻 甘氨酸能突触，2）甘氨酸能和 GABA和甘氨酸的谷氨酸突触反应， 3）阻断甘氨酸摄取对抑制性 反应，4）突触后神经元对甘氨酸能反应的调节 注射cAMP 5）的性质和调节 沉默连接; 6）Mauthner细胞谷氨酸受体α 兴奋性突触 此外，量子响应的计算机模型 将被修改以纳入共激活或 相邻的突触 大多数实验将涉及电压钳位 测量突触电流和递质离子电渗疗法 也将被使用。 这些研究应该为 理解神经网络的涌现特性及其 可塑性，并提出新的机制，外源性 疾病状态中突触传递的调节。

Our long-term objective are to determine the principles of operation of central synapses and of neuronal circuits. We are particularly interested in elucidating properties of the postsynaptic membranes which influence the efficacy and time course of synaptic transmission and which also might provide substrate for neuronal plasticity. Significant postsynaptic properties include the parameters of transmitter-receptor interactions, which should provide a basis for development of rational drug therapies, and structrul parameters. The latter include the receptor or biding site densities, the sub-synaptic location of the receptors, the dimensions of the synaptic contact zone, and the localizations of imputes from the same or different sources., Another important factor is the presence or avsece of transmitter inactivation mechanism which influence the extent to which adjacent synapses interact The proposed research is designed to study central inhibitory (glycinergic) and excitatory (possibly glutamateric): synapses on an identified vertebrate neuron, the ogodfish Mauthner cell, and to develop a computer model of the quanta responses. Much of the work is based on the notion that non-liner interactions between adjacent synapses can be due to lateral diffusion of transmitter from one contact to the next, with, in some cases, allosteric modulation of receptor properties. Specially aims include studying 1) synergistic interactions between adjacent glycinetregic synapses, 2) allosteric regulation of glycinergic and glutamamterigc synaptic responses by GABA and glycine, respectively, 3) effects of blocking glycine uptake on inhibitory responses, 4) modulation of glycinergic responses by postsynaptic injections of cAMP 5) properties and modulation of apparently silent connected , and 6) the glutamate receptor a at Mauthner cell excitatory synapses. Also, a computer model of quanta responses will be modified to incorporate effects of co-activation or adjacent synapses. Most experiments will involve voltage clamp measurements of synaptic currents, and transmitter iontophoresis will also be used. These studies should provide a foundation for understanding emergent properties of neuronal networks and their plasticity and for suggesting new mechanisms for exogenous modulation of synaptic transmission in disease states.