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Publication : Control of sustained attention and impulsivity by G(q)-protein signalling in parvalbumin interneurons of the anterior cingulate cortex.

First Author  Jendryka MM Year  2023
Journal  Transl Psychiatry Volume  13
Issue  1 Pages  243
PubMed ID  37407615 Mgi Jnum  J:337908
Mgi Id  MGI:7508763 Doi  10.1038/s41398-023-02541-z
Citation  Jendryka MM, et al. (2023) Control of sustained attention and impulsivity by G(q)-protein signalling in parvalbumin interneurons of the anterior cingulate cortex. Transl Psychiatry 13(1):243
abstractText  The anterior cingulate cortex (ACC) has been implicated in attention deficit hyperactivity disorder (ADHD). More specifically, an appropriate balance of excitatory and inhibitory activity in the ACC may be critical for the control of impulsivity, hyperactivity, and sustained attention which are centrally affected in ADHD. Hence, pharmacological augmentation of parvalbumin- (PV) or somatostatin-positive (Sst) inhibitory ACC interneurons could be a potential treatment strategy. We, therefore, tested whether stimulation of G(q)-protein-coupled receptors (G(q)PCRs) in these interneurons could improve attention or impulsivity assessed with the 5-choice-serial reaction-time task in male mice. When challenging impulse control behaviourally or pharmacologically, activation of the chemogenetic G(q)PCR hM3Dq in ACC PV-cells caused a selective decrease of active erroneous-i.e. incorrect and premature-responses, indicating improved attentional and impulse control. When challenging attention, in contrast, omissions were increased, albeit without extension of reward latencies or decreases of attentional accuracy. These effects largely resembled those of the ADHD medication atomoxetine. Additionally, they were mostly independent of each other within individual animals. G(q)PCR activation in ACC PV-cells also reduced hyperactivity. In contrast, if hM3Dq was activated in Sst-interneurons, no improvement of impulse control was observed, and a reduction of incorrect responses was only induced at high agonist levels and accompanied by reduced motivational drive. These results suggest that the activation of G(q)PCRs expressed specifically in PV-cells of the ACC may be a viable strategy to improve certain aspects of sustained attention, impulsivity and hyperactivity in ADHD.
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