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

项目摘要/摘要 这项拟议的研究将确定调节听觉事件相关电位(Erp)的中间神经元亚型。 以及听觉皮质的神经振荡活动。ERP被广泛用于识别与翻译相关的内容 生物标记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，事件相关电位背后的大脑皮层回路机制尚不清楚。功能缺乏症 GABA能中间神经元，即小白蛋白阳性(PV)和生长抑素阳性(SOM)神经元， 在塑造企业资源规划变化方面提出了建议。PV和SOM神经元在调节神经元获得性改变中起作用 刺激相关反应和大脑皮层神经反应的同步性。然而，改变的影响 PV和SOM神经元对听觉皮质ERP和神经振荡的作用仍然很差 明白了。这项拟议的研究将整合电生理学和化学遗传学技术，以便 直接操纵听觉皮质(AC)中PV和SOM神经元的活动并表征变化 到事件相关电位和神经振荡。我们将注射携带Cre依赖的腺相关病毒(AAV) 设计师药物(DREADD)对PV-CRE和SOM-CRE AC的特异性激活作用 老鼠。康复后的小鼠将接受DREADD配体Clozaping-N-Oxide或 当小鼠清醒并在隔音环境中自由活动时，将记录车辆和听觉皮质活动 将声音刺激呈现给他们的竞技场。记录静息脑电和事件相关电位，并进行特征分析 静息脑电的伽马和β频率变化及事件相关电位波幅和潜伏期的变化 PV和SOM细胞失活与对照组比较。这项研究的目标是产生新的见解，了解 神经元间功能障碍会导致感觉反应的改变。

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.