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bioRxiv · 10.1101/2021.09.19.460973

Chronic hM4Di-DREADD mediated chemogenetic inhibition of forebrain excitatory neurons in postnatal or juvenile life does not alter adult mood-related behavior

Tiwari, P.·Kapri, D.·Pradhan, A.·Balakrishnan, A.·Chaudhari, P. R.·Vaidya, V. A.
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Abstract

G-protein coupled receptors (GPCRs) coupled to Gi-signaling, in particular downstream of monoaminergic neurotransmission, are posited to play a key role during developmental epochs (postnatal and juvenile), in shaping the emergence of adult anxio-depressive behaviors and sensorimotor gating. To address the role of Gi-signaling in these developmental windows, we used a CamKII-tTA::TRE hM4Di bigenic mouse line to express the hM4Di-DREADD in forebrain excitatory neurons and enhanced Gi-signaling via chronic administration of the DREADD agonist, CNO in the postnatal (PNCNO: postnatal day 2-14) or juvenile (JCNO: postnatal day 28-40) window. We confirmed that the expression of the HA-tagged hM4Di-DREADD was restricted to CamKII-positive neurons in the forebrain, and administration of CNO in postnatal or juvenile windows evoked inhibition in forebrain circuits of the hippocampus and cortex, as indicated by a decline in expression of the neuronal activity marker, c-fos. hM4Di-DREADD mediated inhibition of CamKII-positive forebrain excitatory neurons in postnatal or juvenile life did not impact the weight profile of mouse pups, and also did not influence the normal ontogeny of sensory reflexes. Further, postnatal or juvenile hM4Di-DREADD mediated inhibition of CamKII-positive forebrain excitatory neurons did not alter anxiety or despair-like behaviors in adulthood, and did not impact sensorimotor gating. Collectively, these results indicate that chemogenetic induction of Gi-signaling in CamKII-positive forebrain excitatory neurons in postnatal and juvenile temporal windows does not appear to impinge on the programming of anxio-depressive behaviors in adulthood.

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Tiwari, P., Kapri, D., Pradhan, A., Balakrishnan, A., Chaudhari, P. R., Vaidya, V. A.. 2021-09-21. Chronic hM4Di-DREADD mediated chemogenetic inhibition of forebrain excitatory neurons in postnatal or juvenile life does not alter adult mood-related behavior. https://doi.org/10.1101/2021.09.19.460973

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