EFFECTIVE SYNAPTIC CURRENTS IN MOTONEURONS

我们研究计划的长期目标是了解哺乳动物运动神经元如何整合突触输入并将其转化为放电率的变化。 在这个更新的应用程序的重点是对这些过程中的活性树枝状电导的影响。 许多关于运动神经元中突触整合的先前工作，包括我们自己的工作，都是在麻醉制剂中进行的，其中树突表现为被动的核心导体。 在这些条件下，单个突触电流在通往索马的途中衰减，并且同时激活的突触电流线性地或略小于线性地相加。 然而，在几种类型的未麻醉的动物制剂和脑干和脊髓切片中，运动神经元表达大量的活性树突电导，其显著地改变突触电流到索马的传递和不同突触输入系统的整合。在特定目标1下提出的实验旨在检查在未麻醉的去大脑猫中研究的运动神经元中突触电流的整合。 去大脑动物制备物中下行单胺能纤维的紧张活性促进介导持续内向电流的活性树突电导的表达，导致突触输入的电压依赖性放大。 具体目标2中提出的实验将检查用内部钾通道阻滞剂处理的猫脊髓运动神经元中的突触电流的总和，这也被证明会诱导运动神经元中突触电流的电压依赖性放大。 具体目标3中的实验将使用体外研究的大鼠舌下神经运动神经元的树突分支上的谷氨酸离子电渗来检查影响突触电流向索马的转移的树突机制。 将对运动神经元索马体进行电压钳位，并在不同通道类型的药物阻断前后在不同钳位电位下测量谷氨酸诱发电流。 所有的实验项目都将通过计算机模拟来补充，计算机模拟使用具有不同类型和分布的树突电导的运动神经元的房室模型来帮助解释实验数据。 总的来说，这些实验和模拟项目将提供关于运动神经元整合多个突触输入的新信息，以及运动神经元如何将突触输入转化为频率调制的尖峰序列输出。

The long-term objective of our research program is to understand how mammalian motoneurons integrate synaptic inputs and transform them into changes in firing rate. The focus in this renewal application is on the effects of active dendritic conductances on these processes. Much of the precedent work on synaptic integration in motoneurons, including our own, has been carried out in anesthetized preparations in which the dendrites behave as passive core conductors. Under these conditions, individual synaptic currents are attenuated en route to the soma, and concurrently activated synaptic currents sum linearly or slightly less than linearly. However, in several types of unanesthetized animal preparations and in brain stem and spinal cord slices, motoneurons express a host of active dendritic conductances that dramatically alter the transmission of synaptic current to the soma and the integration of different synaptic input systems. The experiments proposed under Specific Aim 1 are designed to examine the integration of synaptic currents in motoneurons studied in unanesthetized, decerebrate cats. Tonic activity in descending monoaminergic fibers in the decerebrate preparation facilitates the expression of active dendritic conductances that mediate persistent inward currents, leading to a voltage- dependent amplification of synaptic input. The experiments proposed in Specific Aim 2 will examine the summation of synaptic currents in cat spinal motoneurons treated with internal potassium channel blockers, which have also been shown to induce voltage-dependent amplification of synaptic currents in motoneurons. The experiments in Specific Aim 3 will examine the dendritic mechanisms affecting the transfer of synaptic current to the soma, using glutamate iontophoresis onto dendritic branches of rat hypoglossal motoneurons studied in vitro. The motoneuron soma will be voltage-clamped, and the glutamate-evoked current will be measured at different clamp potentials before and after pharmacological blockade of different channel types. All of the experimental projects will be complemented by computer simulations using compartmental models of motoneurons with different types and distributions of dendritic conductances to help interpret the experimental data. Collectively, these experimental and simulation projects will provide new information on the integration of multiple synaptic inputs by motoneurons, and how motoneurons transform synaptic inputs into frequency- modulated spike trains outputs.