Ionic currents and spiking in cerebellar nuclear neurons

小脑核神经元中的离子电流和尖峰

基本信息

批准号：
8118576
负责人：
Indira M Raman
金额：
$ 32.37万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-07-01 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8118576
关键词：
Action Potentials Address Affect Animals Ataxia Autistic Disorder Behavioral Brain region Cells Cerebellar Nuclei Cerebellar cortex structure Cerebellum Characteristics Chemicals Chemosensitization Code Data Dendrites Dyslexia Dystonia Electrophysiology (science)Frequencies Gene Mutation Goals Health Image Injection of therapeutic agent Ion Channel Learning Measures Mediating Modeling Movement Mus Muscle N-Methyl-D-Aspartate Receptors Neurons Nuclear Output Pattern Pharmacology Physiologic pulse Physiological Property Proteins Protocols documentation Purkinje Cells Receptor Activation Recruitment Activity Research Resistance Signal Pathway Signal Transduction Slice Source Staging Stimulus Synapses Synaptic Receptors Synaptic plasticity Testing Therapeutic Intervention Time Work brain cell classical conditioning conditioning eyelid conditioning mind control mossy fiber motor learning neuronal cell body postsynaptic presynaptic prevent research study response synaptic inhibition voltage voltage clamp

Action Potentials Address Affect Animals Ataxia Autistic Disorder Behavioral Brain region Cells Cerebellar Nuclei Cerebellar cortex structure Cerebellum Characteristics Chemicals Chemosensitization Code Data Dendrites Dyslexia Dystonia Electrophysiology (science)Frequencies Gene Mutation Goals Health Image Injection of therapeutic agent Ion Channel Learning Measures Mediating Modeling Movement Mus Muscle N-Methyl-D-Aspartate Receptors Neurons Nuclear Output Pattern Pharmacology Physiologic pulse Physiological Property Proteins Protocols documentation Purkinje Cells Receptor Activation Recruitment Activity Research Resistance Signal Pathway Signal Transduction Slice Source Staging Stimulus Synapses Synaptic Receptors Synaptic plasticity Testing Therapeutic Intervention Time Work brain cell classical conditioning conditioning eyelid conditioning mind control mossy fiber motor learning neuronal cell body postsynaptic presynaptic prevent research study response synaptic inhibition voltage voltage clamp

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项目摘要

DESCRIPTION (provided by applicant): Many neurons of the cerebellum are spontaneously active, firing 10 to 100 action potentials per second even in the absence of synaptic input. This high basal activity correlates with information coding mechanisms that differ from those of cells in circuits that are generally quiescent until excited synaptically. For example, in the cerebellar nuclei, long-term changes in the strength of excitatory synaptic inputs are not generated by classical Hebbian rules of coincident synaptic excitation and postsynaptic firing. Instead, synaptic currents are potentiated by patterns of stimulation that combine inhibition and excitation, in a manner that resembles the activity of (inhibitory) Purkinje afferents and (excitatory) mossy fiber afferents predicted to occur during cerebellar associative learning tasks. Such results support the idea that cerebellar circuits have rules for information transfer and storage that distinguish them from other well studied brain regions. The present proposal is motivated by the question of how spontaneous firing sets the stage for plasticity that is independent of spike timing. In the proposed research, experiments will be performed on neurons of the cerebellar nuclei in cerebellar slices of mice. Voltage-clamp and current-clamp recordings of synaptic responses, ionic currents, and action potentials, as well as imaging of Ca signals in nuclear cell dendrites, will be directed toward identifying the mechanisms of potentiation of excitatory synaptic responses to mossy fiber input, as well as toward examining the influence of spontaneous activity in Purkinje afferents and nuclear cells on plasticity. The resulting data will provide general information about the fundamental properties of signal encoding across brain regions, as well as specific information about the ionic mechanisms underlying cerebellar synaptic plasticity under normal and pathophysiological conditions. PUBLIC HEALTH RELEVANCE: In the present work, we are studying cells in the cerebellum, a part of the brain that controls the learning and execution of coordinated muscle movements, and whose electrical and chemical signaling patterns are disrupted in ataxia, dystonia, dyslexia, and autism. Because signaling patterns by brain cells depend on specialized proteins called ion channels, we are studying the properties of these ion channels, with the goal of understanding how their activity leads to long-lasting changes in cerebellar signals that are important for motor learning. These data can be used to make comparisons to disrupted signals in the cerebella of animals that have ataxia as a result of genetic mutations of ion channels, with the goal of understanding what goes wrong under pathophysiological conditions and whether ion channels can serve as a target for therapeutic interventions.

描述（由申请人提供）：小脑的许多神经元自发活跃，即使在没有突触输入的情况下，也会发射10至100个动作电位。这种高基础活性与信息编码机制相关，这些信息编码机制与电路中的细胞不同，这些机制通常是静止的，直到突触激发。例如，在小脑核中，兴奋性突触输入强度的长期变化不是由古典的Hebbian共同的突触激发和突触后射击产生的。取而代之的是，突触电流通过刺激的模式（结合抑制作用和激发）的模式增强，这种方式类似于（抑制性的）Purkinje传入和（兴奋性的）苔藓纤维传入的活性，预计在小脑相关学习任务期间会发生。这样的结果支持这样的想法：小脑电路具有信息传输和存储规则，可以将它们与其他精心研究的大脑区域区分开来。本提案是由自发射击如何设定独立于尖峰时机的可塑性的问题来激发的。在拟议的研究中，将对小鼠小脑核神经元的神经元进行实验。突触响应，离子电流和动作电位的电压钳和电流钳记录，以及核细胞树突中的CA信号的成像，旨在识别兴奋性突触反应增强对苔藓纤维输入的兴奋性突触反应的机制，并检查对塑料的影响和核细胞的影响和核心的影响。最终的数据将提供有关跨大脑区域信号编码的基本特性的一般信息，以及有关在正常和病理生理条件下小脑突触可塑性下的离子机制的特定信息。公共卫生相关性：在目前的工作中，我们正在研究小脑中的细胞，这是控制和执行协调的肌肉运动的大脑的一部分，其电和化学信号传导模式在共济失调，肌张力障碍，全障碍和自闭症中受到破坏。由于脑细胞的信号传导模式取决于称为离子通道的专用蛋白质，因此我们正在研究这些离子通道的特性，目的是了解它们的活性如何导致小脑信号的持久变化，这对于运动学习很重要。这些数据可用于对由于离子通道的遗传突变而导致的动物小脑中的破坏信号进行比较，目的是了解病理生理条件下的问题以及离子通道是否可以作为治疗性干预措施的靶标。