Cortical Circuits of Interhemispheric Communication

半球间通讯的皮层回路

基本信息

批准号：
9888369
负责人：
Alfonso J Apicella
金额：
$ 29.4万
依托单位：
UNIVERSITY OF TEXAS SAN ANTONIO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-10 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9888369
关键词：
Action Potentials Address Affect Architecture Area Auditory Auditory area Axon Behavior Brain Stem Cells Central Auditory Processing Disorder Communication Contralateral Corpus Callosum Electrophysiology (science)Enterobacteria phage P1 Cre recombinase Equilibrium Experimental Models Foundations In Vitro Inferior Colliculus Interneurons Ipsilateral Knowledge Label Left cerebral hemisphere Measures Mus Neurobiology Neurons Output Parvalbumins Pathology Pathway interactions Patients Physiological Production Psyche structure Research Role Schizophrenia Sensory Signal Transduction Social Behavior Somatostatin Sound Localization Source Specificity Speech Structure Symptoms Synapses Testing Verbal Auditory Hallucinations Work auditory pathway auditory processing autism spectrum disorder cell type clinically relevant communication behavior experience experimental study hippocampal pyramidal neuron in vivo information processing neuronal patterning neuropathology optogenetics patch clamp photoactivation postsynaptic recruit response sensory input sound

项目摘要

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.

项目摘要/摘要听觉间跨性传播仍然是神经生物学的谜。处理听觉信号皮质水平需要两个半球之间的感觉输入协调。异常电路潜在的半球间交流可能解释了沟通和社会行为的赤字在自闭症谱系障碍（ASD）和听觉言语幻觉（AVH）中观察到，其中一种精神分裂症的显着症状，影响约70％的患者。但是，组织和这些电路的功能尚不清楚。下丘（IC）是一个主要的处理中心听觉路径。特别是，IC是处理用于本地化声音的信息的主要中心太空中的来源。重要的是，在听觉皮层（AC）的第5层中，神经元的子集投影到IC （CCOL神经元）和对侧AC（CCOT神经元）。 Callosal对5层单元的预测起源于 AC的第2/3层和第5层。确定第2/3和第5层的功能效应和连通性对这些神经元上的callosal预测对于了解这两者的听觉处理至关重要皮质和皮质下水平。该提议的目的是剖析是否两层对对侧皮层有相似的影响。在特别是，这两个层都可以激发CCOL并抑制CCORT神经元。或者，特定于层的刺激可能对5层神经元有不同的影响，并且输入与CCOL和CCORT神经元的平衡不同有助于这些神经元的不同反应。我们的发现将为了解第2/3层和第5层callosal预测在皮质和皮层调节中的作用两个半球之间感觉输入的连续性所需的听觉处理。该提案的目的是（1）确定第2/3和第5层的突触组织对AC中的CCORT和CCOL神经元的投影。（2）建立callosal dionnnnaptic的突触机制抑制AC中的CCORT和CCOL神经元。（3）确定光学遗传过程中AC中的诱发响应刺激第2/3层和第5层的呼叫预测。解决这些目标的方法将使用小鼠作为实验模型，逆行和光遗传学标记，特定的光学记录定义途径和体内电生理学中的突触连通性，以量化兴奋性和神经元的抑制性成分，腔内和层次的投影特异性在Callosal预测的光激活期间招募。从这项工作中发现将是重要的因为它们将提供有关AC神经元电路和功能方面的基本知识有助于与皮质神经病理学相关的临床上明确通信。