Synaptic basis for cortical tonal receptive field

描述（由申请人提供）：初级听觉皮层（Al）的大多数生理学研究都集中在神经脉冲输出上。然而，为了理解听觉皮层神经元的处理和计算，有必要研究皮层反应特性背后的突触机制，即在各种声音刺激下，将皮层细胞的突触输入与其输出联系起来。在我们的初步研究中，我们已经开发了听觉皮层神经元的体内全细胞记录技术，以建立对皮层反应的突触连接基础的基本理解。在这里，我建议系统地描述突触输入，从兴奋性和抑制性输入的角度，在单个A1神经元的频率调谐和频率强度音调接受野（TRFs）的阈上/阈下结构的基础上。在目标1中，我将讨论音调输入是如何由单个人工智能神经元表示的。我将利用体内全细胞电流箝法记录声诱发膜电位反应，确定单个A1神经元阈下trf与阈上trf的空间关系，并表征阈下trf随A1神经元特征频率（CFs）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光谱时间相互作用在形成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将通过在体全细胞电压钳记录得到。特别是，我将确定皮质抑制在形成频率调谐和trf中的作用。在Aim 3中，我将描述丘脑皮质和皮质内成分对单个A1神经元兴奋性突触TRFs的贡献，方法是利用药理学方法使皮质内连接沉默。随着对兴奋性输入的起源的理解，A1神经元TRFs背后的突触输入电路的基本模型将被构建。作为起点，本项目将专门针对成年大鼠A1输入层（3-4层）组织学上确定的兴奋性锥体神经元。这项研究将是我们初步研究的直接延伸，并将为理解听觉皮层中声音处理和表征的皮层机制提供必要的信息。综上所述，全细胞记录技术在这些研究中的应用将为解决有关听觉皮层反应机制的基本问题提供独特的机会，也可能为理解听觉皮层的生理和病理提供新的信息水平。

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.