A role for SHANK3 in social reward

Reversal of social deficits: Mice in which SHANK3 is downregulated in the ventral tegmental area (shShank3) display a time-dependent loss of social interest in the three-chamber social interaction test compared with control mice (scrShank3). These social deficits are reversed by administration of an mGluR1 positive allosteric modulator (Ro 677476) during early postnatal development. Normalized SP2: social preference during the second half of the 10-minute test over the total social preference. Image from Bariselli S. et al. (2016).

Impaired function of the reward circuitry has been suggested to contribute to social deficits in autism. In the current study, SFARI Investigator Christian Lüscher and his colleague Camilla Bellone examined mice in which expression of the autism risk gene SHANK3 was downregulated in the ventral tegmental area — a key brain region involved in reward. These mice exhibit altered excitatory synapse transmission that converges to reduce dopaminergic neuron activity and generates impaired social behaviors. Importantly, the synaptic, circuit and behavioral deficits in these mice are ameliorated by administration of a type 1 metabotropic glutamate receptor (mGluR1) agonist during early postnatal development. These results provide further support for the importance of reward circuit function in the control of social behaviors, and suggest mGluR1 modulation as a potential therapeutic strategy for some forms of autism.

SHANK3 controls maturation of social reward circuits in the VTA.

Bariselli S., Tzanoulinou S., Glangetas C., Prévost-Solié C., Pucci L., Viguié J., Bezzi P., O'Connor E.C., Georges F., Lüscher C., Bellone C.

Nat. Neurosci. 19, 926-934

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