GABAB MEDIATED DISINHIBITION IN THE DENTATE GYRUS

GABAB 介导的齿状回抑制解除

• 批准号: 3413772
• 负责人: DARRELL V LEWIS
• 金额: $ 10.97万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3413772
• 关键词: GABA receptor; axon; biological models; dentate gyrus; electrical potential; electrophysiology; histology; interneurons; laboratory rat; long term potentiation; neural information processing; neural inhibition; neural initiation; neural transmission; neuropharmacology; pertussis toxin; synapses

This project will explore how inhibition is controlled in the dentate gyrus of the rat hippocampal slice. There are poorly understood disinhibitory mechanisms in the brain that transiently suppress inhibitory interneuron function. Setting the level of inhibitory neuron function has profound effects on neural plasticity such as long term potentiation, a model of learning, and on paroxysmal activity such as seizures. The dentate gyrus provides an excellent model system for the study of disinhibitory mechanisms because profound transient suppression of recurrent inhibition can be triggered in the dentate by a single conditioning stimulus to the adjacent alveus or stratum lucidum of the hippocampus. This phenomenon will herein be refered to as stimulus induced disinhibition or SID. Previous work in this laboratory has shown that GABAB receptor agonists disinhibit the dentate. The work proposed here will explore the hypothesis that SID in the dentate is due to GABAB mediated inhibition of inhibitory basket cells. In these experiments, recurrent inhibition is evoked in the dentate gyrus of the rat hippocampal slice by stimulation of the mossy fibers (granule cell axons). Inhibition is measured by its effect on the extracellular granule cell population spike triggered by a stimulus to the perforate path. SID is induced by stimulation of alveus or stratum recording methods will be used to study SID in the dentate. The specific aims are to determine: 1) Whether other GABAB receptor antagonists will block SID and the long, late, presumably GABAB mediated inhibitory postsynaptic potentials in the dentate; 2) If inhibitory postsynaptic potentials in granule cells are suppressed during SID; 3) If SID facilitates long term potentiation of synaptic transmission in the dentate gyrus; 4) If basket cells are inhibited by GABAB inhibitory postsynaptic potentials during SID.

该项目将探讨如何在齿状回中控制抑制作用 大鼠海马切片的 有鲜为人知的抑制性 大脑中瞬时抑制抑制性中间神经元的机制 功能。 设置抑制神经元功能的水平具有深刻的 对神经可塑性的影响，例如长期增强，一种模型 学习和阵发性活动，例如癫痫发作。 齿状回 为研究提供了出色的模型系统 机制是因为深刻的瞬时抑制反复抑制 可以通过单个调节刺激在牙齿中触发 海马的邻近肺肺泡或叶片层。 这个现象 此处将被称为刺激引起的抑制作用或SID。 该实验室的先前工作表明GABAB受体激动剂 DISIND抑制牙齿。 这里提出的工作将探讨该假设 牙齿中的SID是由于GABAB介导的抑制作用 篮细胞。 在这些实验中，在齿状回中引起了复发性抑制作用 通过刺激苔藓纤维（颗粒）的大鼠海马切片 细胞轴突）。 抑制是通过对细胞外的影响来衡量的 由刺激触发的颗粒细胞种群尖峰 小路。 SID是由刺激牙槽或层记录方法诱导的 将用于研究牙齿中的SID。 具体目的是确定：1​​）是否其他GABAB受体 拮抗剂将阻止SID和长期，晚，大概是Gabab介导的 牙齿抑制性突触后潜能； 2）如果抑制性 在SID期间，颗粒细胞中的突触后电位被抑制； 3）如果 SID有助于长期增强突触传播 齿回； 4）如果篮细胞被GABAB抑制作用抑制 SID期间的突触后潜力。