The functional role of trace amine-associated receptors (TAARs) in genetically modified mouse strains (KO TAARs)

Project: Grant fulfilmentGrant stage fulfilment

Project Details

Description

The aim of the project is to investigate the functional role of trace amine-associated receptors (TAARs). It is proposed to study the neurophysiological and behavioral characteristics of genetically modified mouse strains knocked out for one of the TAARs (TAAR1 and TAAR5). The task is to study such neurophysiological mechanisms as sensory gating, mismatch negativity, pre-pulse inhibition, and to assess the consequences of stressful influences. The scientific novelty of the project means that for the first time, such neurophysiological (mismatch negativity, sensory gating) and behavioral mechanisms (pre-pulse inhibition), which play an important role in the norm and in various pathological conditions, will be studied in mouse strains with gene knockout of TAARs receptors. A complex of the three most significant endophenotypes of schizophrenia, altered in main disorders and observed both at different stages of the disease development and in the patients' relatives, is presented for study (Light, Swerdlow, 2015). The study will be conducted by a chronic experiment in mice with implanted epidural electrodes.
An important component of the study is to evaluate the effect of knockout of TAARs receptors on stress effects. Currently, the study of TAARs contribution to the development of post-stress disorders is fragmentary. The trace amine-associated receptors role in the regulation of CNS electrophysiological parameters of activity after the action of stressors by recording the evoked brain potentials - sensory gating (sensory dosing) and electrophysiological correlates of the mechanisms of involuntary attention - generation of mismatch negativity (MMN) have not yet been studied. The relevance of the problem of stress, the study of mechanisms of its development and the search for stress-protective drugs is beyond doubt. In this regard, a comprehensive study of stress effect on the evoked brain potentials - sensory gating and electrophysiological correlates of involuntary attention - the mismatch negativity; pre-pulse inhibition to elucidate the mechanisms of neural networks functioning by using knockout animals (KO TAARs) will allow to study more completely the contribution of TAARs to the biochemical basis of electrophysiological and behavioral indicators of brain dysfunctions, as well as to shed light on the possible pathophysiological consequences of TAARs receptor dysfunction.
AcronymRSF_SRG_2022 - 1
StatusActive
Effective start/end date1/01/2231/12/22

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