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: 6394270
• 负责人: Indira M Raman
• 金额: $ 22.05万
• 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/6394270
• 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，其功能的破坏会导致各种运动障碍。小脑皮层的浦肯野神经元整合了许多大脑区域的信号，形成了抑制性突触到小脑核的神经元，该神经元被广泛射出。尽管这种突触在小脑功能中很重要，但小脑核神经元的电性能在很大程度上尚不清楚。这些神经元即使在Purkinje神经元自发抑制率的高速率中，这些神经元也会发射自发作用电位。活性的这种持久性必须部分源于小脑核神经元的固有的离子通道的性质。此外，浦肯野细胞中的快速信号传导可能导致神经递质的耗竭，从而降低突触后抑制的水平。所提出的实验将确定小脑核神经元自发性发射的基础离子电流，并确定来自Purkinje细胞的抑制性突触输入的模式，这些模式成功地调节小脑核神经元的发射。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基本要素是至关重要的，特别是突触抑制是否必然会使突触后细胞沉默，或者有时是否可以启用或增强发射。小脑核神经元将通过从幼鼠中分离出酶促，并用于用于用通道特异性阻滞剂在药理学上分离的电流的高质量电压记录。电流将通过由动作电势波形组成的电压钳命令唤起电流，从而可以直接测量有助于射击的电流。在视觉控制下，小脑切片将用于记录小脑核神经元对Purkinje神经元中唤起的高频发射的反应。特定神经元类中电流的这种实验度量对于开发精确的神经活动计算机模型以及小脑功能和功能障碍的系统级研究的细胞解释至关重要。