DYNAMICS OF GABAERGIC INHIBITION IN THE SUBTHALAMUS

描述：(摘自申请人的摘要) 兴奋性丘脑底核是神经元的主要驱动力 动物和人类在静息状态下基底节的活动， 在自主运动期间以及在特发性和实验性模型中 帕金森氏症。丘脑底核的活动受 相互连接的苍白球外球对GABA能的抑制。 这项研究的总体目标是确定以下原则 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 脑片中的丘脑下丘脑神经元的数量将被用来检验 GABA能抑制性突触后电位/电流(GABA IPSPs/IPSCs) 自发的或驱使的有节奏的射击。GABA IPSP/IPSC的爆发将是 以确定GABA是否作用于-A和/或-B 受体可以在丘脑下部神经元产生反弹的爆发式放电。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。含有完整丘脑的切片 多巴胺激动剂存在下的苍白球外核群网络 或拮抗剂将被研究以确定是自发的还是诱发的爆发 丘脑下部神经元的放电可以触发低频振荡活动。 单个苍白球神经元将通过细胞旁标记在体内填充 它们在丘脑底核的突触周围将绘制成三幅图 并通过光学和电子显微镜检查以确定 邻近的神经元接受共同的输入。分歧的程度和 苍白球投影中的会聚将由体视学确定 丘脑底核内GABA能终末的估计 网络中的神经元数量。

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.