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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：
8312596
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/8312596
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

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）：小脑的许多神经元是自发活动的，即使在没有突触输入的情况下，每秒也能激发10至100个动作电位。这种高基础活动与信息编码机制相关，该机制不同于回路中通常处于静止状态直到突触兴奋的细胞的机制。例如，在小脑核中，兴奋性突触输入强度的长期变化不是由经典的Hebbian规则产生的，即突触兴奋和突触后放电。相反，突触电流的增强模式的刺激，结合联合收割机抑制和兴奋，在某种程度上类似于活动的（抑制性）浦肯野传入和（兴奋性）苔藓纤维传入预测发生在小脑联想学习任务。这些结果支持了这样一种观点，即小脑回路具有信息传递和存储的规则，这些规则将它们与其他研究充分的大脑区域区分开来。本提案的动机是自发放电如何设置阶段的可塑性，是独立的尖峰时间的问题。在拟议的研究中，实验将在小鼠小脑切片的小脑核神经元上进行。电压钳和电流钳记录的突触反应，离子电流和动作电位，以及成像的钙信号在核细胞树突，将被定向到识别的机制增强的兴奋性突触反应苔藓纤维输入，以及对检查自发活动的影响浦肯野传入和核细胞的可塑性。由此产生的数据将提供一般信息的基本特性的信号编码跨大脑区域，以及特定的信息下正常和病理生理条件下的小脑突触可塑性的离子机制。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，小脑是大脑的一部分，控制着协调肌肉运动的学习和执行，其电和化学信号模式在共济失调，肌张力障碍，阅读障碍和自闭症中被破坏。由于脑细胞的信号模式依赖于称为离子通道的特殊蛋白质，我们正在研究这些离子通道的特性，目的是了解它们的活动如何导致小脑信号的长期变化，这些变化对运动学习很重要。这些数据可用于与因离子通道基因突变而导致共济失调的动物小脑中的中断信号进行比较，目的是了解在病理生理条件下出现了什么问题以及离子通道是否可以作为治疗干预的目标。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Antagonism of lidocaine inhibition by open-channel blockers that generate resurgent Na current.

DOI：
10.1523/jneurosci.3026-12.2013
发表时间：
2013-03-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Bant JS;Aman TK;Raman IM
通讯作者：
Raman IM

Synaptic inhibition, excitation, and plasticity in neurons of the cerebellar nuclei.

DOI：
10.1007/s12311-009-0140-6
发表时间：
2010-03
期刊：
CEREBELLUM
影响因子：
3.5
作者：
Zheng, Nan;Raman, Indira M.
通讯作者：
Raman, Indira M.

Prolonged postinhibitory rebound firing in the cerebellar nuclei mediated by group I metabotropic glutamate receptor potentiation of L-type calcium currents.

DOI：
10.1523/jneurosci.1834-11.2011
发表时间：
2011-07-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Zheng N;Raman IM
通讯作者：
Raman IM

Cross-species conservation of open-channel block by Na channel β4 peptides reveals structural features required for resurgent Na current.

DOI：
10.1523/jneurosci.1428-11.2011
发表时间：
2011-08-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Lewis AH;Raman IM
通讯作者：
Raman IM

Inwardly permeating Na ions generate the voltage dependence of resurgent Na current in cerebellar Purkinje neurons.

DOI：
10.1523/jneurosci.0376-10.2010
发表时间：
2010-04-21
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Aman TK;Raman IM
通讯作者：
Raman IM