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

描述（由申请人提供）：增益控制机制介导神经元传递函数，并动态地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。神经元增益的这种连续调整使编码效率最大化。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通过对紧张性兴奋性的影响来调节输入-输出功能，但局部回路在改变受控刺激期间的增益控制中的作用仍然不确定。 在这里，我们建议检查本地电路在编码听觉刺激在清醒（未麻醉）小鼠体内的作用，使用高二价阳离子阻断本地电路，从而使我们能够分离的电路特性的影响，从那些外在的输入在中枢神经系统中的编码信息。下丘是中脑听觉核团，其神经元分为兴奋性和抑制性两种不同的局部回路。这些非线性回路决定了声音强度的动态范围，不同的局部回路的神经元中产生不同的速率水平函数。我们将测试的假设，即激活的局部电路在下丘是必要的编码的声音强度，听觉编码的功能，需要输入招聘，并表现出症状的动态增益控制，和声音强度编码是一个新兴的属性的IC。更重要的是，成功地使用高的二价阳离子分离局部电路的影响，从外在的输入在体内将成为一个非常有价值的工具，在系统以外的听觉系统的CNS功能的研究，将是一个重大的进展，在CNS的病理状态的研究。 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作用。因此，有必要开发一种工具，可以普遍使用来区分神经编码的这两个特征，以便可以理解它们对神经系统反应的单独影响。通过这种方式，可以更好地理解神经系统的正常功能以及病理疾病状态。在这个提议中，我们的目标是开发这些工具来研究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加工的机制。

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.