Cortical Circuits of Interhemispheric Communication

项目摘要/摘要 听觉半球间通信仍然是一个神经生物学之谜。听觉信号的处理在 大脑皮层水平需要两个半球之间的感觉输入协调。异常电路 潜在的大脑半球间沟通可以解释沟通和社会行为方面的缺陷 自闭症谱系障碍(ASD)和听觉言语幻觉(AVH)是最常见的 精神分裂症的突出症状，影响到大约70%的患者。然而，该组织和 这些电路的功能仍不清楚。下丘是脑内的主要加工中心。 听觉通路。特别地，IC是用于定位声音的信息处理的主要中心 太空中的资源。重要的是，听觉皮质(AC)第5层的一部分神经元投射到IC (CCol神经元)和对侧AC(CORT神经元)。向第5层细胞的胼胝体投射起源于 交流的第2/3层和第5层。确定第2/3层和第5层的功能效果和连通性 在这些神经元上的胼胝体投射对于理解两者的听觉处理是至关重要的。 皮质和皮质下水平。 这项建议的目的是分析这两个层面是否对对侧皮质有类似的影响。在……里面 具体地说，两层神经元均可兴奋CCol，抑制CCort神经元。或者，特定于层的刺激 可能对第5层神经元有不同的影响，对CCol和Ccort神经元的输入平衡也不同 对这些神经元的不同反应有贡献。我们的发现将建立一个新的框架 了解第2/3层和第5层胼胝体投射在皮质和皮质下调节中的作用 两个半球之间的感觉输入的连续性所需的听觉处理。 本方案的目的是：(1)确定第2/3层和第5层的突触组织 AC向CCort和CCol神经元的投射。(2)建立穹隆双突触的突触机制 对AC中CCort和CCol神经元的抑制作用。(3)在光发生过程中测定AC的音调诱发反应 刺激第2/3层和第5层的膝盖骨投射。解决这些目标的方法将使用 以小鼠为实验模型，逆行和光遗传标记，特异性光生理记录 以及体内电生理学来量化兴奋性和 层间、层内的抑制成分和神经元的亚类投射特异性 在膝盖骨投射的光激活过程中被招募。这项工作的发现将是重大的 因为它们将提供有关交流神经元电路和功能方面的基础知识 有助于大脑半球间的通讯，这在临床上与皮质神经病理学有关。

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.