Synaptic circuitry mechanisms for auditory cortical processing

描述(申请人提供)：了解皮质突触回路的结构是理解听觉皮质中信息表示和处理的关键。然而，由于技术的限制，皮质突触回路的一般结构，以及这种结构如何决定皮质功能，在很大程度上仍不清楚。作为解决这个问题的第一步，在这个项目中，我们将研究单个皮质神经元功能反应背后的兴奋性和抑制性突触输入的模式，并揭示决定或塑造这些反应特性的突触机制。在听觉皮质中，突触输入的模式可以在很大程度上由其频率强度的音调感受野(TRFs)来反映。这些模式代表了作为单个皮质神经元功能基础的突触输入电路的基本结构特性。利用活体全细胞记录技术，我们将确定成年大鼠听皮层输入层兴奋性神经元和抑制性神经元突触输入的“光谱时间”模式。我们将通过药物沉默大脑皮层来剖析兴奋性输入的丘脑皮质成分。被记录的神经元的细胞类型将由它们的尖峰和形态特性决定。我们将通过活体全细胞电压钳记录技术揭示兴奋性和抑制性突触输入的模式，以确定皮层锥体神经元频率/强度调节的兴奋性和抑制性突触机制。我们将通过开发一种新的药理学方法来有效和特定地沉默皮质，来阐明丘脑皮质兴奋性输入对皮质神经元反应特性的贡献。最后，通过根据组织学和生理学区分皮质抑制神经元，我们将确定皮质GABA能中间神经元的反应特性，以及它们潜在的突触机制。

DESCRIPTION (provided by applicant): Understanding the structure of cortical synaptic circuits is key to comprehending information representation and processing in the auditory cortex. However, due to technical limitations, the general structure of cortical synaptic circuits, and how this structure determines cortical function, remains largely unknown. As a first step to addressing this issue, in this project, we will investigate the patterns of excitatory and inhibitory synaptic inputs underlying the functional responses of individual cortical neurons and reveal the synaptic mechanisms determining or shaping these response properties. In the auditory cortex, patterns of synaptic inputs can be largely reflected by their frequency-intensity tonal receptive fields (TRFs). These patterns represent basic structural properties of synaptic input circuitry underlying the functioning of individual cortical neurons. Using an in vivo whole-cell recording technique, we will determine the "spectrotemporal" pattern of synaptic inputs for both excitatory and inhibitory neurons in the input layers of the adult rat auditory cortex. We will dissect the thalamocortical components of excitatory inputs by pharmacologically silencing the cortex. The cell type of recorded neurons will be determined by their spiking and morphological properties. We will determine excitatory and inhibitory synaptic mechanisms for the frequency/ intensity tuning of cortical pyramidal neurons by revealing the patterns of excitatory and inhibitory synaptic inputs with in vivo whole-cell voltage-clamp recording techniques. We will explicate the contribution of thalamocortical excitaotry inputs to the response properties of cortical neurons by developing a novel pharmacological approach to effectively and specifically silence the cortex. Finally, by distinguishing cortical inhibitory neurons according to histology and physiology, we will determine response properties of cortical GABAergic interneurons, and their underlying synaptic mechanisms.