Synaptic basis for cortical tonal receptive field

描述（由申请人提供）：初级听觉皮层（Al）中的大多数生理学研究都集中在神经尖峰输出上。然而，为了理解听觉皮层神经元执行的处理和计算，有必要研究皮层响应特性的突触机制，即将皮层细胞的突触输入与它们在各种声音刺激下的输出相关联。在我们的试点研究中，我们已经开发出在体内的听觉皮层神经元的全细胞记录技术，以建立一个基本的理解皮层反应的突触连接的基础。在这里，我建议系统地表征突触输入，兴奋性和抑制性输入，潜在的频率调谐和超/阈下结构的频率强度音调感受野（TRFs）的单个A1神经元。在目标1中，我将讨论音调输入如何由单个AI神经元表示。本研究采用在体全细胞电流钳方法记录单个A1神经元的声诱发膜电位，研究阈下和阈上TRFs之间的空间关系，并以A1神经元的特征频率（CFs）表征阈下TRFs的变化。在目标2中，我将确定兴奋性和抑制性突触输入之间的spectrotemporal相互作用在塑造Al神经元的频率调谐和TRFs中的作用。纯兴奋性和抑制性突触输入的TRF将通过使用体内全细胞电压钳记录来导出。特别是，我将确定在形成频率调谐和TRFs的皮质抑制的作用。在目标3中，我将利用药理学方法沉默的皮质内连接的特点的贡献丘脑皮质和皮质内组件的兴奋性突触TRFs的单个A1神经元。了解兴奋性输入的来源后，我们将建立A1神经元TRFs的突触输入回路的基本模型。作为一个起点，这个项目将专门针对组织学确定的兴奋性锥体神经元的输入层（层3-4）的成年大鼠A1。这项研究将是我们的试点研究的直接延伸，并将产生必要的信息，了解听觉皮层的声音处理和代表的皮层机制。总之，在这些研究中应用全细胞记录技术将提供独特的机会，以解决有关的听觉皮层反应的机制的基本问题，也可能产生新的水平的信息，以了解听觉皮层的生理和病理。

DESCRIPTION (provided by applicant): Most physiological studies in the primary auditory cortex (Al) have focused on neural spike output. However, to understand the processing and computation performed by auditory cortical neurons, it is necessary to examine the synaptic mechanisms underlying cortical response properties, i.e. to correlate the synaptic inputs of cortical cells with their outputs under various sound stimuli. In our pilot studies, we have developed techniques of in vivo whole-cell recording from auditory cortical neurons, as to establish a fundamental understanding of the synaptic connection basis for cortical responses. Here, I propose to systematically characterize the synaptic inputs, in terms of both excitatory and inhibitory inputs, underlying the frequency tuning and the supra-/sub-threshold structure of the frequency-intensity tonal receptive fields (TRFs) of single A1 neurons. In Aim 1, I will address how the tonal inputs are represented by a single Al neuron. I will determine the spatial relationship between supra- and sub-threshold TRFs of single A1 neurons, by recording tone-evoked membrane potential responses with in vivo whole-cell current-clamp method, and also characterize the change of subthreshold TRFs with the characteristic frequencies (CFs) of A1 neurons. In Aim 2, I will determine the role of spectrotemporal interaction between excitatory and inhibitory synaptic inputs in shaping the frequency tuning and TRFs of Al neurons. TRFs of pure excitatory and inhibitory synaptic inputs will be derived by using in vivo-whole-cell voltage-clamp recording. In particular, I will determine the role of the cortical inhibition in shaping the frequency tuning and TRFs. In Aim 3, I will characterize the contributions of thalamocortical and intracortical components to the excitatory synaptic TRFs of single A1 neurons by exploiting pharmacological approaches to silent the intracortical connections. With the understanding of the origins of the excitatory inputs, a basic model of synaptic input circuits underlying the TRFs of A1 neurons will be constructed. As a starting point, this project will specifically target the histologically determined excitatory pyramidal neurons in the input layers (layer 3-4) of adult rat A1. This study will be a direct extension of our pilot studies, and will generate information essential for understanding the cortical mechanisms underlying sound processing and representation in the auditory cortex. Taken together, the application of whole-cell recording technique in these studies will provide unique opportunities to address the fundamental issues concerning the mechanisms underlying auditory cortical responses, and are also likely to yield new level of information to the understanding of physiology and pathology of the auditory cortex.