IONIC CURRENTS AND SPIKING IN CEREBELLAR NUCLEAR NEURONS

小脑核神经元中的离子电流和尖峰

• 批准号: 6197962
• 负责人: Indira M Raman
• 金额: $ 24.55万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6197962
• 关键词: GABA receptor; action potentials; brain electrical activity; cerebellar Purkinje cell; cerebellar cortex; cerebellar nuclei; laboratory mouse; neural conduction; sodium channel; synapses; voltage /patch clamp; voltage gated channel

The cerebellum is involved in motor control, and disruption of its function can lead to a variety of movement disorders. Purkinje neurons of the cerebellar cortex, which integrate signals from many brain regions, form inhibitory synapses onto neurons of the cerebellar nuclei, which project widely. Despite the importance of this synapse in cerebellar function, the electrical properties of cerebellar nuclear neurons are largely unknown. These neurons fire spontaneous action potentials, even during high rates of spontaneous inhibition from Purkinje neurons. This persistence of activity must partly result from the properties of ion channels intrinsic to cerebellar nuclear neurons. Additionally, rapid signaling in Purkinje cells may lead to a depletion of neurotransmitter, reducing the level of postsynaptic inhibition. The proposed experiments will identify ionic currents underlying spontaneous firing in cerebellar nuclear neurons, as well as determine the patterns of inhibitory synaptic input from Purkinje cells that successfully modulate firing in cerebellar nuclear neurons. Understanding this interaction between synaptic and intrinsic currents is central to understanding a basic element of the neural code, specifically, whether synaptic inhibition necessarily silences a postsynaptic cell or whether it sometimes enables or enhances firing. Cerebellar nuclear neurons will by enzymatically isolated from young mice and used for high-quality voltage-clamp recordings of currents that are pharmacologically isolated with channel-specific blockers. Currents will be evoked by voltage-clamp commands consisting of action potential waveforms, allowing direct measurements of the currents contributing to firing. Cerebellar slices, under visual control, will be used to make recordings of responses of cerebellar nuclear neurons to high- and low- frequency firing evoked in Purkinje neurons. Such experimental measures of the currents in specific neuronal classes is essential to the development of accurate computer models of neural activity, as well as to cellular interpretations of systems-level studies of cerebellar function and dysfunction.

小脑参与运动控制，其功能障碍可导致各种运动障碍。小脑皮质的浦肯野神经元整合了来自多个脑区的信号，与广泛投射的小脑核神经元形成抑制性突触。尽管这种突触在小脑功能中很重要，但小脑核神经元的电特性在很大程度上是未知的。这些神经元发射自发动作电位，即使在浦肯野神经元自发抑制率很高的情况下也是如此。这种持续的活动一定部分是由小脑核神经元固有的离子通道特性造成的。此外，浦肯野细胞中的快速信号可能会导致神经递质耗尽，从而降低突触后抑制的水平。拟议的实验将确定小脑核神经元自发放电背后的离子电流，以及确定成功调节小脑核神经元自发放电的浦肯野细胞抑制性突触输入的模式。了解突触和内在电流之间的这种相互作用对于理解神经代码的一个基本元素是至关重要的，具体地说，突触抑制是否一定会使突触后细胞沉默，或者它是否有时会启动或增强放电。小脑核神经元将通过酶法从幼鼠中分离出来，并用于高质量的电压钳记录电流，这些电流是用通道特异性阻滞剂药物隔离的。电流将通过由动作电位波形组成的电压钳位命令来激发，从而允许直接测量导致触发的电流。在视觉控制下，小脑切片将被用来记录小脑核神经元对浦肯野神经元诱发的高频和低频放电的反应。这种对特定神经元类别电流的实验测量对于开发准确的神经活动计算机模型以及对系统水平的小脑功能和功能障碍的细胞解释至关重要。