Characterizing Changes to Event-Related Potentials and Neural Oscillations in the Auditory Cortex Following Inactivation of Parvalbumin and Somatostatin Interneurons.

表征小白蛋白和生长抑素中间神经元失活后听觉皮层事件相关电位和神经振荡的变化。

• 批准号: 10464758
• 负责人: Mawaheb Kassir
• 金额: $ 4.14万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10464758
• 关键词: Aging; Attenuated; Auditory; Auditory area; Biological Markers; Brain; Cell physiology; Cells; D Cells; Dependovirus; Disease; Electrodes; Electroencephalogram; Electrophysiology (science); Event-Related Potentials; Frequencies; Functional disorder; Goals; High Frequency Oscillation; Human; Injections; Interneurons; Left; Ligands; Measures; Mediating; Membrane; Motor; Movement; Mus; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neurons; Oxides; Parvalbumins; Pattern; Periodicity; Phase; Play; Population; Recovery; Research; Rest; Role; Sensory; Shapes; Somatostatin; Stimulus; Techniques; Testing; age related; autism spectrum disorder; awake; base; cell type; clinically relevant; density; designer receptors exclusively activated by designer drugs; hearing impairment; inhibitory neuron; insight; mouse model; novel; relating to nervous system; response; sensory stimulus; sound; voltage

Project Summary/Abstract The proposed study will identify interneuron subtypes that regulate the auditory event-related potential (ERP) and neural oscillatory activity in the auditory cortex. The ERP is widely-used to identify translationally relevant biomarkers and to characterize sensory deficits implicated in autism spectrum disorders, aging and hearing loss. However, the cortical circuit mechanisms that underlie the ERP are unknown. Functional deficits in GABAergic interneurons, namely parvalbumin-positive (PV) and somatostatin-positive (SOM) neurons, have been suggested in shaping ERP changes. PV and SOM neurons play a role in regulating the gain of stimulus-related responses and synchrony of neural responses in the cortex. However, the impact of altered PV and SOM neuron function on the ERP and neural oscillations in the auditory cortex remains poorly understood. The proposed study will integrate electrophysiology and chemogenetic techniques in order to directly manipulate the activity of PV and SOM neurons in the auditory cortex (AC) and characterize changes to the ERP and to neural oscillations. We will inject an adeno-associated virus (AAV) carrying Cre-dependent designer receptors exclusively activated by designer drugs (DREADD) into the AC of PV-Cre and SOM-Cre mice. Following recovery mice will receive systemic injections of the DREADD ligand clozaping-n-oxide or vehicle and auditory cortical activity will be recorded as mice are awake and freely moving in a sound-insulated arena where sound stimuli will be presented to them. We will record resting EEG and ERP and characterize changes in gamma and beta frequencies in the resting EEG and changes in ERP amplitude and latency during PV and SOM cell inactivation compared to control. The goal of this study is to generate novel insights into how interneuron dysfunction leads to altered sensory responses.

项目总结/摘要 这项研究将确定调节听觉事件相关电位（ERP）的中间神经元亚型 和听觉皮层的神经振荡活动。ERP被广泛用于识别与业务相关的 生物标志物和表征与自闭症谱系障碍、衰老和听力有关的感觉缺陷 损失然而，ERP背后的皮层回路机制是未知的。功能缺陷， GABA能中间神经元，即小清蛋白阳性（PV）和生长抑素阳性（SOM）神经元，具有 在塑造ERP变革方面提出了建议。PV和SOM神经元在调节神经元的获得方面发挥作用 刺激相关反应和皮层神经反应的同步性。然而，改变的影响 PV和SOM神经元对ERP和听皮层神经振荡的作用仍然很差 明白拟议的研究将整合电生理学和化学遗传学技术，以 直接操纵听觉皮层（AC）中PV和SOM神经元的活动并表征变化 ERP和神经振荡。我们将注射一种腺相关病毒（AAV）， 设计者受体专门由设计者药物（DREADD）激活进入PV-Cre和SOM-Cre的AC 小鼠恢复后，小鼠将接受DREADD配体氯扎平-n-氧化物或 当小鼠清醒并在隔音的环境中自由移动时，记录载体和听觉皮层活动。 竞技场，在那里声音刺激将呈现给他们。我们将记录静息脑电和脑电波并进行表征 静息EEG中γ和β频率的变化以及 与对照相比，PV和SOM细胞失活。这项研究的目的是产生新的见解，如何 中间神经元功能障碍导致感觉反应改变。