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

描述（由申请人提供）：听觉系统的主要任务是处理声音刺激中包含的时间和强度信息，它通过整合来自不同来源的兴奋性和抑制性输入来完成。在中枢神经系统中，这种整合发生的第一个核团是下丘（IC）。IC是脑干核。它接收来自脑干中大多数听觉核团的直接输入，并反过来将几乎所有的输入提供给听觉前脑。除了在听觉处理中的重要性外，IC还是导致声音诱发癫痫发作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，兴奋性的输入和内在的神经元特性的调节还没有被调查，和一个基本电路的定义，定义类的细胞和连接是必要的，以了解其功能。我们最近证明，兴奋性和抑制性输入IC选择性调节增益控制和神经元兴奋性。这种增益控制的调节决定了IC中的神经元对声音强度的编码能力。我们还发现了证据，局部兴奋性循环回路中的IC。此外，活动以复杂的方式在IC的两侧之间传播。我们将结合联合收割机电生理记录的活动在单个神经元，光学监测的神经元群体响应与电压敏感染料和计算建模技术，以解决以下具体目标：1。确定模式化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.确定丘间连接的要求。我们的研究结果将描绘的网络和细胞组件设置在正常的听觉系统的兴奋性的限制，并将进一步我们的理解的因素，导致过度兴奋状态，引起癫痫发作。

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.