Cortical Circuits of Interhemispheric Communication

项目概要/摘要 听觉半球间的交流仍然是一个神经生物学之谜。听觉信号的处理. 皮层水平需要两个半球之间的感觉输入的协调。异常电路 潜在的大脑半球间的沟通可以解释沟通和社会行为的缺陷 在自闭症谱系障碍（ASD）和听觉语言幻觉（AVH）中观察到， 精神分裂症的突出症状，影响约70%的患者。然而，该组织和 这些电路的功能仍然不清楚。下丘（IC）是大脑中的一个主要加工中心。 听觉通路特别地，IC是用于处理用于定位声音的信息的主要中心 太空中的源。重要的是，听觉皮层（AC）第5层中的神经元子集投射到IC (CCol神经元）和对侧AC（CCort神经元）。胼胝体向第5层细胞的投射起源于 AC的2/3层和5层。确定第2/3层和第5层的功能效果和连通性 胼胝体投射到这些神经元上，对于理解听觉处理过程和 皮质和皮质下水平。 本建议的目的是解剖两层是否对侧皮质有相似的影响。在 特别是，两层都能兴奋CCol神经元并抑制CCort神经元。或者，层特异性刺激 可能对第5层神经元有不同的影响，对CCol和CCort神经元的输入有不同的平衡 导致了这些神经元的不同反应。我们的研究结果将建立一个新的框架， 理解胼胝体第2/3层和第5层投射在皮质和皮质下神经元调制中的作用 两个半球之间的感觉输入的连续性所需的听觉处理。 本研究的目的是：（1）确定胼胝体第2/3层和第5层的突触结构 投射到AC中的CCort和CCol神经元。(2)建立胼胝体双突触的突触机制 抑制AC中的CCort和CCol神经元。(3)在光遗传学期间确定AC中的音调诱发反应 刺激胼胝体第2/3层和第5层投射。实现这些目标的方法将使用 以小鼠为实验模型，逆行标记和光遗传标记，特异性光生理记录 突触连接的定义的途径，并在体内电生理学定量的兴奋性和 层间、板内和神经元投射特异性亚类的抑制成分 在胼胝体投射的光活化过程中招募。这项工作的发现将具有重要意义 因为它们将提供关于AC神经元的电路和功能方面的基础知识 有助于临床上与皮质神经病理学相关的半球间通信。

PROJECT SUMMARY/ABSTRACT Auditory interhemispheric communication remains a neurobiological mystery. Processing of auditory signals at cortical level requires coordination of sensory input between the two hemispheres. Abnormal circuitry underlying interhemispheric communication may explain deficits in communication and social behavior observed in autism spectrum disorders (ASD) and auditory verbal hallucinations (AVH), one of the most prominent symptoms in schizophrenia, affecting approximately 70% of patients. However, the organization and functionality of these circuits remain unclear. The inferior colliculus (IC) is a major processing center in the auditory pathways. Particularly, IC is a major center for processing of information used in localizing sound sources in space. Importantly, a subset of neurons, in the layer 5 of the auditory cortex (AC), project to the IC (CCol neurons) and to the contralateral AC (CCort neurons). Callosal projections to layer 5 cells originate in layer 2/3 and layer 5 of AC. Determining the functional effects and connectivity of layer 2/3 and layer 5 callosal projections onto these neurons is critical for understanding auditory processing at both cortical and subcortical levels. The objective of this proposal is to dissect if both layers have a similar effect on the contralateral cortex. In particular, both layers could excite CCol and inhibit CCort neurons. Alternatively, layer-specific stimulation could have differing effects on layer 5 neurons, and a different balance of input to CCol and CCort neurons contributing to different responses of these neurons. Our findings will establish a new framework for understanding the roles of layer 2/3 and layer 5 callosal projections in the modulation of cortical and subcortical auditory processing required for the continuity of sensory input between the two hemispheres. The aims of this proposal are (1) Determine the synaptic organization of layer 2/3 and layer 5 callosal projections onto CCort and CCol neurons in AC. (2) Establish the synaptic mechanism of callosal disynaptic inhibition onto CCort and CCol neurons in AC. (3) Determine tone-evoked responses in AC during optogenetic stimulation of layer 2/3 and layer 5 callosal projections. The approach for addressing these aims will use the mouse as the experimental model, retrograde and optogenetic labeling, specific opto-physiological recordings of synaptic connectivity in defined pathways, and in vivo electrophysiology to quantify the excitatory and inhibitory component of the interlaminar, intralaminar, and the subclass projection specificity of the neurons recruited during photoactivation of the callosal projections. Discoveries from this work will be significant because they will provide foundational knowledge regarding circuit and functional aspects of AC neurons contributing to interhemispheric communication which is clinically relevant to cortical neuropathologies.