DYNAMICS OF GABAERGIC INHIBITION IN THE SUBTHALAMUS

底丘脑 GABA 能抑制的动力学

• 批准号: 6317293
• 负责人: Mark D Bevan
• 金额: $ 23.8万
• 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/6317293
• 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：（从申请人的摘要中） 兴奋性丘脑下核是神经元的主要驱动力 在静止条件下动物和人类的基底神经节中的活动， 在自愿运动以及特发性和实验模型中 帕金森氏病。丘脑核的活性受 与相互连接的外部球pallidus抑制GABA能抑制。 这项研究的总体目的是确定原则 丘脑下核中的GABA能抑制作用和抑制作用 帕金森氏病。穿孔贴片，全细胞或细胞外记录 切片中丘脑神经元的 GABA能抑制性突触后电位/电流（GABA IPSP/IPSCS） 自发或驱动的节奏射击。 GABA IPSP/IPSC的爆发将是 在丘脑下神经元中诱发，以确定GABA是否作用于-a和/或-b 受体可以在丘脑下神经元中产生反弹爆发。的作用 多巴胺在调节GABA能突触传播中 将检查丘脑下核。含有完整丘脑的切片 在多巴胺激动剂的存在下 或将研究拮抗剂以确定自发还是诱发的爆发 丘脑下神经元的发射可以触发低频振荡活性。 单个苍白神经元将使用并置标记在体内填充 并将其在丘脑下核中的突触胸部绘制在三个 尺寸并通过光和电子显微镜检查，以确定是否是否 相邻的神经元会收到共同的输入。分歧和 苍白投影中的收敛性将从立体学确定 丘脑核和已知的丘脑核中GABA能末端的估计值 网络中的神经元数。