Role of VTA dopamine neurons and neuroligin 3 in sociability traits related to nonfamiliar conspecific interaction

Sebastiano Bariselli, Hanna Hörnberg, Clément Prévost-Solié, Stefano Musardo, Laetitia Hatstatt-Burklé, Peter Scheiffele and Camilla Bellone ()
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Sebastiano Bariselli: University of Geneva
Hanna Hörnberg: Biozentrum of the University of Basel
Clément Prévost-Solié: University of Geneva
Stefano Musardo: University of Geneva
Laetitia Hatstatt-Burklé: Biozentrum of the University of Basel
Peter Scheiffele: Biozentrum of the University of Basel
Camilla Bellone: University of Geneva

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Atypical habituation and aberrant exploration of novel stimuli have been related to the severity of autism spectrum disorders (ASDs), but the underlying neuronal circuits are unknown. Here we show that chemogenetic inhibition of dopamine (DA) neurons of the ventral tegmental area (VTA) attenuates exploration toward nonfamiliar conspecifics and interferes with the reinforcing properties of nonfamiliar conspecific interaction in mice. Exploration of nonfamiliar stimuli is associated with the insertion of GluA2-lacking AMPA receptors at excitatory synapses on VTA DA neurons. These synaptic adaptations persist upon repeated exposure to social stimuli and sustain conspecific interaction. Global or VTA DA neuron-specific loss of the ASD-associated synaptic adhesion molecule neuroligin 3 alters the behavioral response toward nonfamiliar conspecifics and the reinforcing properties of conspecific interaction. These behavioral deficits are accompanied by an aberrant expression of AMPA receptors and an occlusion of synaptic plasticity. Altogether, these findings link impaired exploration of nonfamiliar conspecifics to VTA DA neuron dysfunction in mice.

Date: 2018
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DOI: 10.1038/s41467-018-05382-3

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