DYNAMICS OF GABAERGIC INHIBITION IN THE SUBTHALAMUS

底丘脑 GABA 能抑制的动力学

• 批准号: 6639735
• 负责人: Mark D Bevan
• 金额: $ 3.16万
• 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 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6639735
• 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：（来自申请人摘要） 兴奋性丘脑底核是神经元活动的主要驱动力， 在静息条件下动物和人类基底神经节的活动， 在自发运动和自发性和实验性模型中， 帕金森氏症。丘脑底核的活动受 GABA能抑制来自连接的外部苍白球。 本研究的总体目标是确定 健康人和老年人丘脑底核GABA能抑制的基础 帕金森氏症。穿孔贴片、全细胞或细胞外记录 的丘脑底神经元切片将被用来检查的影响， GABA能抑制性突触后电位/电流（GABA ipsps/ipscs） 自发的或被驱动的有节奏的放电。GABA ipsps/ipscs的爆发将 在底丘脑神经元中诱发，以确定GABA是否作用于-A和/或-B 受体可以在底丘脑神经元中产生反弹爆发放电。的作用 多巴胺在GABA能突触传递调节中的作用 将检查丘脑底核。包含完整底丘脑的切片 多巴胺激动剂存在下的核-外苍白球网络 或拮抗剂进行研究，以确定是否自发或诱发爆发 底丘脑神经元中的放电可以触发低频振荡活动。 单个苍白球神经元将在体内填充使用单细胞标记 它们在丘脑底核中的突触终扣将被绘制成三个 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。分歧的程度和 苍白球投影的会聚将由体视学确定。 估计GABA能终端在丘脑底核和已知的 网络中的神经元数量。