Regulation of excitability in a sensory system by cellular and network components

通过细胞和网络组件调节感觉系统的兴奋性

• 批准号: 7586699
• 负责人: SHOBHANA SIVARAMAKRISHNAN
• 金额: $ 24.17万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7586699
• 关键词: Address; Auditory; Auditory system; Axon; Behavior; Brain; Brain Stem; Cell Nucleus; Cells; Code; Complex; Computer Simulation; Coupling; Divalent Cations; Dyes; Electrodes; Elements; Epilepsy; Equilibrium; Excitatory Synapse; Frequencies; Glycine Receptors; Inferior Colliculus; Inhibitory Synapse; Injection of therapeutic agent; Lateral lemniscus; Lead; Limb structure; Link; Location; Measures; Membrane; Midbrain structure; Monitor; N-Methylaspartate; Neuraxis; Neurons; Optics; Patch-Clamp Techniques; Pattern; Physiological; Play; Population; Process; Property; Prosencephalon; Rattus; Recurrence; Regulation; Research Personnel; Role; Route; Seizures; Shapes; Shock; Side; Site; Slice; Source; Specificity; Stimulus; Synapses; Synaptic Receptors; Techniques; Testing; Thalamic structure; Training; auditory nuclei; cell type; extracellular; in vivo; neuronal cell body; neuronal excitability; programs; research study; response; sensory system; sound; voltage

DESCRIPTION (provided by applicant): A principal task of the auditory system is to process the temporal and intensity information contained in a sound stimulus, which it does by integrating excitatory and inhibitory input from different sources. The first nucleus in the central nervous system, where such integration occurs, is the inferior colliculus (IC). The IC is a brainstem nucleus. It receives direct input from most of the auditory nuclei in the brainstem and, in turn, provides nearly all of the input to the auditory forebrain. In addition to its importance in auditory processing, the IC is the site of origin of pathological hyperexcitability that leads to sound-evoked seizures. Despite its strategic location and extensive input convergence, the regulation of excitability by inputs and intrinsic neuronal properties has not been investigated, and the definition of a basic circuit in terms of defined classes of cells and connections is necessary to understand its function. We recently demonstrated that excitatory and inhibitory inputs to the IC selectively regulate gain control and neuronal excitability. This regulation of gain control determines how well neurons in the IC can code sound intensity. We have also found evidence for local excitatory recurrent circuits in the IC. Furthermore, activity is propagated in a complex fashion between the two sides of IC. We will combine electrophysiological recordings of activity in single neurons, optical monitoring of neuronal population responses with voltage-sensitve dyes and computational modeling techniques to address the following specific aims: 1. Determine how patterned synaptic input regulates the excitatory/inhibitory ratio in single IC neurons. 2. Determine the importance of cell type specificity in local and inter-collicular circuitry. 3. Determine the requirements for inter-collicular connectivity. Our results will delineate the constraints on excitability in the normal auditory system set by network and cellular components, and will further our understanding of the factors that lead to the hyperexcitable state that gives rise to epileptic seizures.

描述(申请人提供)：听觉系统的一个主要任务是处理声音刺激中包含的时间和强度信息，这是通过整合来自不同来源的兴奋性和抑制性输入来完成的。中枢神经系统中发生这种整合的第一个核是下丘(IC)。IC是一个脑干核团。它接受来自脑干中大多数听觉核团的直接输入，进而向听觉前脑提供几乎所有的输入。除了在听觉处理中的重要性外，IC还是导致声诱发癫痫的病理性过度兴奋的起源部位。尽管它的战略位置和广泛的输入收敛，但尚未研究输入和内在神经元属性对兴奋性的调节，根据定义的细胞和连接类别的基本电路的定义是理解其功能所必需的。我们最近证明，兴奋性和抑制性输入到IC选择性地调节增益控制和神经元的兴奋性。这种对增益控制的调节决定了IC中神经元编码声音强度的能力。我们还发现了IC中存在局部兴奋性循环回路的证据。此外，活动在IC的两侧之间以一种复杂的方式传播。我们将结合单个神经元活动的电生理记录、神经元群体反应的光学监测与电压敏感染料和计算建模技术来解决以下具体目标：1.确定模式突触输入如何调节单个IC神经元的兴奋/抑制比。2.确定细胞类型特异性在局部和丘间回路中的重要性。3.确定节间连通的要求。我们的结果将勾勒出正常听觉系统中网络和细胞成分对兴奋性的限制，并将进一步理解导致癫痫发作的过度兴奋状态的因素。