Effects of mGlu4 knock-down in the nucleus accumbens and basolateral amygdala of wild-type mice

Abstract

Autism Spectrum Disorders (ASD) are neuro-developmental pathologies characterized by social communication and interaction deficiency, and repetitive and restricted behaviors. The social motivation network, notably the nucleus accumbens (NAc), is dysfunctional in these disorders. We previously showed that pharmacological treatment facilitating the activity of the mGlu4 glutamate receptor relieves autistic symptoms in the Oprm1 -/- mouse model of autism. Interestingly, we also evidenced that mGlu4 can modulate the activity of the amygdala, a critical brain region for emotional responses and social behavior. Aim: Our hypothesis is mGlu4 in the NAc and the basolateral amygdala (BLA) plays a critical role in modulating autism-sensitive symptoms, namely social motivation and stereotyped behaviors. Methods : In order to test this, we performed the knockdown of the gene coding for mGlu4, Grm4 , in the nucleus accumbens or the basolateral amygdala of wild-type mice using bilateral stereotaxic injections of shRNA-expressing AAVs. We tested them in several behavioral tests to evaluate the presence or not of autistic symptoms. Results: Knocking down (KD) of Grm4 expression in NAc neurons induces autistic-like symptoms such as impaired social interactions and social preference Conclusions : These results suggest that mGlu4 receptors expressed in the NAc and BLA neurons play a major role in modulating sociability in mice.