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: 7846450
• 负责人: SHOBHANA SIVARAMAKRISHNAN
• 金额: $ 33.46万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-17 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7846450
• 关键词: Auditory; Auditory system; Behavior; Biological Neural Networks; Brain Stem; Categories; Cell Nucleus; Cells; Characteristics; Code; Complex; Contralateral; Disease; Divalent Cations; Ear; Employment; Equilibrium; Exhibits; Frequencies; Funding; Future; Hearing; Individual; Inferior Colliculus; Injection of therapeutic agent; Knowledge; Limb structure; Location; Mainstreaming; Mammals; Mediating; Midbrain structure; Mus; Nature; Nervous System Physiology; Nervous system structure; Network-based; Neuraxis; Neurons; Output; Pattern; Play; Population; Postdoctoral Fellow; Principal Investigator; Process; Property; Recovery; Recruitment Activity; Regulation; Research; Role; Route; Seizures; Sensory; Shapes; Signal Transduction; Site; Solutions; Specificity; Stimulus; Symptoms; Synapses; Synaptic Potentials; Synaptic Receptors; Synaptic plasticity; System; Techniques; Testing; Thalamic structure; Whole-Cell Recordings; Work; auditory stimulus; awake; base; cell type; extracellular; gamma-Aminobutyric Acid; in vivo; patch clamp; pressure; programs; public health relevance; relating to nervous system; response; segregation; sensory system; sound; tool; voltage gated channel

DESCRIPTION (provided by applicant): Gain control mechanisms mediate neuronal transfer functions, and dynamically adjust a neuron or neural system's output response range to match the range of its input signal. This continuous adjustment of neuronal gain maximizes coding efficiency. Individual neurons regulate their output gain primarily through multiplication of excitatory and inhibitory inputs, with further enhancement by voltage- gated channels. In many sensory nuclei in the CNS, neurons may be part of extensive local circuits, but although spontaneous activity in local circuits has been shown to modulate input-output functions through an effect on tonic excitability, the role of local circuitry in gain control during a changing controlled stimulus remains undefined. Here we propose to examine the role of local circuits in coding auditory stimuli in vivo in awake (unanesthetized) mice using high-divalent cations to block local circuits, thus allowing us to separate the effects of circuit properties from those of extrinsic inputs in coding information in the CNS. Neurons in the inferior colliculus, an auditory midbrain nucleus, are segregated into different excitatory and inhibitory local circuits. These non-linear circuits determine the dynamic range of sound intensity, with different rate-level functions arising in neurons that are parts of different local circuits. We will test the hypothesis that the activation of local circuits in the inferior colliculus is necessary for coding sound intensity, a feature of auditory coding that requires input recruitment, and exhibits symptoms of dynamic gain control, and that sound intensity coding is an emergent property of the IC. More importantly, the successful use of high-divalent cations to separate local circuit effects from extrinsic inputs in vivo will become a very valuable tool for the study of CNS function in systems other than the auditory system and will be a major advance in the study of pathological states in the CNS. PUBLIC HEALTH RELEVANCE: The coding of information in the central nervous system is a complex task that requires the synergistic interaction between the properties of individual nerve cells and the neural networks formed between large populations of nerve cells. It is thus necessary to develop a tool which can be used ubiquitously to separate these two features of neural coding, so that their individual influences on responses in the nervous system can be understood. In this manner, both the normal functioning of the nervous system as well as pathological disease states can be better understood. In this proposal we aim to develop these tools to examine the coding of sound information in the auditory system of mammals. This will help elucidate the mechanism of normal and pathological auditory processing.

描述（由申请人提供）：增益控制机制介导神经元传递函数，并动态调整神经元或神经系统的输出响应范围以匹配其输入信号的范围。这种神经元增益的连续调整可以最大限度地提高编码效率。单个神经元主要通过兴奋性和抑制性输入的倍增来调节其输出增益，并通过电压门控通道进一步增强。在中枢神经系统的许多感觉核中，神经元可能是广泛的局部回路的一部分，但是尽管局部回路中的自发活动已被证明可以通过对强直兴奋性的影响来调节输入输出功能，但在变化的受控刺激期间局部回路在增益控制中的作用仍然不明确。 在这里，我们建议使用高二价阳离子阻断局部电路来检查清醒（未麻醉）小鼠体内局部电路在编码听觉刺激中的作用，从而使我们能够将电路特性的影响与中枢神经系统编码信息中的外在输入的影响分开。下丘（听觉中脑核）中的神经元被分为不同的兴奋性和抑制性局部回路。这些非线性电路决定声音强度的动态范围，作为不同局部电路一部分的神经元中出现不同的速率级别函数。我们将测试以下假设：下丘局部电路的激活对于编码声音强度是必要的，这是听觉编码的一个特征，需要输入募集，并表现出动态增益控制的症状，并且声音强度编码是 IC 的一个新兴属性。更重要的是，成功利用高二价阳离子将局部电路效应与体内外源输入分开，将成为研究听觉系统以外系统中中枢神经系统功能的非常有价值的工具，并将成为中枢神经系统病理状态研究的重大进展。 公共卫生相关性：中枢神经系统中的信息编码是一项复杂的任务，需要单个神经细胞的特性与大量神经细胞之间形成的神经网络之间的协同相互作用。因此，有必要开发一种可以普遍使用的工具来区分神经编码的这两个特征，以便能够理解它们各自对神经系统反应的影响。通过这种方式，可以更好地了解神经系统的正常功能以及病理疾病状态。在本提案中，我们的目标是开发这些工具来检查哺乳动物听觉系统中声音信息的编码。这将有助于阐明正常和病理性听觉处理的机制。