Our suggestion focuses on determining the causal role of serotonin (5-HT) in controlling inhibition in cortical activity and its implications for working memory maintenance. 5-HT controls inhibition in the prefrontal cortex (PFC) via various receptors that are expressed preferentially in different GABAergic cell types. In addition, aberrant GABAergic neurotransmission in the PFC is a key component of the pathophysiology of schizophrenia and depression. However, currently existing 5-HT signalling medications have addressed a variety of mental health problems but not typically cognitive capacities. As a result, determining the causative role of each 5-HT receptor is crucial. Understanding the circuit mechanism of working memory requires an understanding of the effects of particular GABAergic cell types on circuit activity. Then we’ll be able to create new, effective treatments. To capture cortical activity at the mesoscopic and local levels, this study will use cell type-specific optical voltage imaging methods, including wide-field and two-photon imaging. First, as well-trained mice perform a delayed Go or No-Go auditory task, we will simultaneously monitor pyramidal and 5-HT receptor-specific GABAergic cell types, as well as apply pharmacological 5-HT modulation to monitor and characterise serotonin-related changes in cortical dynamics and behaviour. Then we’ll combine optical and magnetic imaging. During the execution of the above-mentioned delayed task, optogenetic silencing was used to dissect the function of several 5-HT receptor-specific GABAergic cell types. Finally, we’ll employ computer modelling to provide quantitative descriptions of brain networks in order to better understand the working memory circuit dynamics. Models can aid in the prediction of mental diseases and the tracking of disease progression.
Author (S) Details
University of Barcelona, Catalonia, Spain.
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