DYNAMICS OF GABAERGIC INHIBITION IN THE SUBTHALAMUS

底丘脑 GABA 能抑制的动力学

• 批准号: 6540397
• 负责人: Mark D Bevan
• 金额: $ 17.75万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6540397
• 关键词: GABA receptor; Parkinson's disease; action potentials; dopamine; electron microscopy; evoked potentials; laboratory mouse; laboratory rat; lenticular nucleus; light microscopy; neural transmission; neurochemistry; neurons; neurotransmitter antagonist; subthalamus; synapses; tissue /cell culture; voltage /patch clamp

DESCRIPTION:(from applicant's abstract) The excitatory subthalamic nucleus is a major driving force of neuronal activity in the basal ganglia of animals and humans under resting conditions, during voluntary movement and in idiopathic and experimental models of Parkinson's disease. The activity of the subthalamic nucleus is regulated by GABAergic inhibition from the reciprocally connected external globus pallidus. The overall objective of this research is to determine the principles that underlie GABAergic inhibition in the subthalamic nucleus in health and in Parkinson's disease. Perforated patch, whole-cell or extracellular recordings of subthalamic neurons in slices will be used to examine the effects of GABAergic inhibitory postsynaptic potentials/currents (GABA ipsps/ipscs) on spontaneous or driven rhythmic firing. Bursts of GABA ipsps/ipscs will be evoked in subthalamic neurons to determine whether GABA acting at -A and/or -B receptors can produce rebound burst firing in subthalamic neurons. The role of dopamine in the regulation of GABAergic synaptic transmission in the subthalamic nucleus will be examined. Slices containing an intact subthalamic nucleus-external globus pallidus network in the presence of dopamine agonists or antagonists will be studied to determine whether spontaneous or evoked burst firing in subthalamic neurons can trigger low frequency oscillatory activity. Single pallidal neurons will be filled in vivo using juxtacellular labelling and their synaptic boutons in the subthalamic nucleus will be plotted in three dimensions and examined by light and electron microscopy to determine whether neighbouring neurons receive common inputs. The degree of divergence and convergence in the pallidal projection will be determined from stereological estimates of GABAergic terminals in the subthalamic nucleus and the known numbers of neurons in the network.

描述：（来自申请人的摘要） 兴奋性底丘脑核是神经元的主要驱动力 动物和人类在休息条件下基底神经节的活动， 在随意运动期间以及特发性和实验模型中 帕金森病。丘脑底核的活动受以下因素调节 来自相互连接的外部苍白球的 GABA 能抑制。 本研究的总体目标是确定以下原则： 健康和人的底丘脑核 GABA 能抑制的基础 帕金森病。穿孔贴片、全细胞或细胞外记录 切片中的底丘脑神经元将用于检查 GABA 能抑制性突触后电位/电流 (GABA ipsps/ipscs) 自发或驱动有节奏的射击。 GABA ipsps/ipscs 的爆发将会 在丘脑底神经元中诱发以确定 GABA 是否作用于 -A 和/或 -B 受体可以在丘脑底神经元中产生反弹爆发放电。的作用 多巴胺对 GABA 能突触传递的调节 将检查丘脑底核。含有完整底丘脑的切片 多巴胺激动剂存在下的核外苍白球网络 或拮抗剂将被研究以确定是自发的还是诱发的爆发 丘脑底神经元的放电可以触发低频振荡活动。 使用近细胞标记在体内填充单个苍白球神经元 它们在丘脑底核中的突触纽扣将被绘制成三个 尺寸并通过光学和电子显微镜检查以确定是否 相邻的神经元接收共同的输入。分歧程度和 苍白球投影的收敛性将由体视学确定 丘脑底核中 GABA 能末端的估计和已知的 网络中神经元的数量。