Monoamines, via their G-protein coupled receptors (GPCRs) are known to affect mood behaviours. Monoaminergic signalling dysfunction in early critical window of life is known to be associated with perturbed anxio-depressive behaviours in adulthood. We wanted to understand how Gq/Gi balance in early life can have long term consequences on schizoaffective disorders. To do this, we chronically activated or inhibited forebrain excitatory neurons in different critical epochs of life. We saw that chronically enhanced hM3Dq-mediated Gq signalling in forebrain excitatory neurons in early postnatal life, but not in juvenile or adult windows of life, can result in enhanced anxiety, despair and schizophrenia-like behaviour in adult animals. However, as a contrast, inhibition of forebrain excitatory neurons via enhanced hM4Di-mediated Gi signalling in any of these three windows of life did not affect schizoaffective disorders in adulthood.
We also explored the effects of acute hM3Dq and hM4Di DREADD-mediated activation of Gq and Gi signalling respectively in adulthood. We observed that increased Gq-mediated activation of forebrain excitatory neurons resulted in a significant decline in anxiety-like behaviour but did not have an effect on despair-like behaviour, whereas increased Gi-mediated inhibition of of forebrain excitatory neurons did not result in changes in either anxiety or despair-like behaviour.
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