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

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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.