Chemogenetic inhibition of the amygdala modulates emotional behavior expression in infant rhesus monkeys

Abstract

Statement of SignificanceMany neurodevelopmental disorders exhibit abnormal structural or functional amygdala development and alterations in socioemotional behavior. To date, developmental neuroscience studies have relied on permanent lesions techniques to investigate how atypical amygdala development impacts socioemotional behaviors, which may not adequately recapitulate the role of amygdala dysfunction in the manifestation of aberrant behavior. The present study sought to demonstrate that the designer receptors exclusively activated by designer drugs (DREADDs) chemogenetic tool could transiently inhibit amygdala activity in infant monkeys resulting in alterations in socioemotional behavior. This proof-of-principle study supports the use of chemogenetics for developmental neuroscience research, providing an opportunity to broaden our understanding of how changes in neuronal activity across early postnatal development influences behavior and clinical symptoms. Infant Chemogenetic Amygdala Inhibition

Chronic hM4Di-DREADD-Mediated Chemogenetic Inhibition of Forebrain Excitatory Neurons in Postnatal or Juvenile Life Does Not Alter Adult Mood-Related Behavior

“…Prior evidence indicates that transient hM4Di-DREADD inhibition of the amygdala in infant rhesus monkeys has long-lasting effects on emotionality, with a decline noted in fear and anxiety responses (Raper et al, 2019). A study also shows that constitutive overexpression of the Gi-coupled 5-HT 1A receptors (Kusserow et al, 2004) can program decreased anxiety-like behavior in adulthood.…”