ACETYLCHOLINE MODULATION OF NEURONAL EXCITABILITY

四位对离子通道和离子通道有长期兴趣的研究人员 突触生物学联合起来研究乙酰胆碱的作用 (ACh)关于中枢离子通道的激活和调制 神经系统。ACh有效浓度的变化或 ACh受体(AChRs)的数量与认知有关 正常受试者和非受试者的精神障碍、注意力缺陷、记忆丧失 阿尔茨海默病患者、帕金森病患者和药物寻求者 行为。本计划项目中描述的工作包括分析 尼古丁和毒扁豆碱的机制可能会揭示这些 精神错乱。该计划是从协作项目中自然发展而来的 四名调查员已经开始调查了。我们计划一起调查 营养家族神经调节蛋白对烟碱受体的调节 大脑中表达的因子；尼古丁和毒扁豆碱的作用 受体在调节突触传递中的作用；ACh对 几种电压门控离子通道的分布和作用 G蛋白偶联钾通道(GIRKs)对神经元的调节 开火。我们将研究大脑的几个不同区域，包括 海马体、黑质、腹侧被盖区、球部 苍白球、内侧缰核、脚间核和小脑。 将使用几种制剂，包括新鲜解离的 神经元、神经细胞培养物、脑片和转基因小鼠。 主要的工具是电生理，因为我们主要关心的是 ACh引起的突触功能和神经元放电的变化 模式。这些项目密切相关，互动已经 出现了极大地促进了每个领域的进展。这些相互作用 将拓宽我们今后的工作范围。

Four investigators with long standing interest in ion channels and synaptic biology have come together to study effects of acetylcholine (ACh) on the activation and modulation of ion channels in the central nervous system. Changes in the effective concentration of ACh or in the number of ACh receptors (AChRs) have been associated with cognitive disorders, attention deficits, memory loss in normal subjects and in Alzheimer's patients, in Parkinson's Disease and in drug seeking behaviors. Work described in this Program Project includes analyses of nicotinic and muscarinic mechanisms that may shed light on these disorders. The Program developed naturally out of collaborative projects already begun by the four investigators. Together, we plan to investigate the regulation of nicotinic AChRs by neuregulins, a family of trophic factors expressed in the brain; the role of nicotinic and muscarinic receptors in modulating synaptic transmission; the modulation by ACh of several types of voltage gated ion channels; the distribution and role of G-protein coupled potassium channels (GIRKs) in regulating neuronal firing. Several different regions of the brain will be studied including the hippocampus, substantia nigra, ventral tegmental area, globus pallidus, medial habenula, interpeduncular nucleus, and cerebellum. Several preparations will be employed including freshly dissociated neurons, nerve cell cultures, brain slices and genetically altered mice. The primary tools are electrophysiological as we are primarily concerned with ACh induced changes in synaptic function and neuronal firing patterns. The projects are closely related and interactions have already emerged that greatly facilitate progress in each area. These interactions will broaden the scope of our work in the future.