POSTSYNAPTIC FACTORS AFFECTING SYNAPTIC EFFICACY

我们的长期目标是确定以下原则 中枢突触和神经元回路的运作。我们是 尤其对阐明该化合物的性质感兴趣 影响疗效和时程的突触后膜 突触传递，也可能提供底物 对于神经元的可塑性。显著的突触后特性 包括递质-受体相互作用的参数，这些参数 应该为合理的药物疗法的发展提供基础， 和结构参数。后者包括受体或 结合部位密度，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推算。另一个重要的 因素是发射器失活的存在或持续时间 影响相邻突触程度的机制 互动建议的研究旨在研究中心 抑制性(甘氨酸能)和兴奋性(可能是谷氨酸)： 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。 许多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侧向扩散 从一个触点到下一个触点的发射器，在某些情况下， 受体特性的变构调节。特别瞄准 包括研究1)相邻区域之间协同作用 Glycinetregic突触，2)甘氨酸能和 GABA和甘氨酸对谷氨酸的突触反应， 3)阻断甘氨酸摄取对抑制作用的影响 反应，4)突触后对甘氨酸能反应的调节 注射cAMP 5)性质和调制表面 静默连接，6)毛特纳细胞谷氨酸受体a 兴奋性突触。此外，量子响应的计算机模型 将被修改以纳入共同激活的影响或 相邻的突触。大多数实验将涉及电压钳位 突触电流和递质离子导入的测量 也将被使用。这些研究应该为以下方面提供基础 理解神经元网络的涌现特性及其 可塑性和提出外源基因的新机制 疾病状态下突触传递的调节。

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.