EthoLoop: automated closed-loop neuroethology in naturalistic environments.

Accurate tracking and analysis of animal behavior is crucial for modern systems neuroscience. However, following freely moving animals in naturalistic, three-dimensional (3D) or nocturnal environments remains a major challenge. Here, we present EthoLoop, a framework for studying the neuroethology of freely roaming animals. Combining real-time optical tracking and behavioral analysis with remote-controlled stimulus-reward boxes, this system allows direct interactions with animals in their habitat. EthoLoop continuously provides close-up views of the tracked individuals and thus allows high-resolution behavioral analysis using deep-learning methods. The behaviors detected on the fly can be automatically reinforced either by classical conditioning or by optogenetic stimulation via wirelessly controlled portable devices. Finally, by combining 3D tracking with wireless neurophysiology we demonstrate the existence of place-cell-like activity in the hippocampus of freely moving primates. Taken together, we show that the EthoLoop framework enables interactive, well-controlled and reproducible neuroethological studies in large-field naturalistic settings.

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

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.

SHANK3 controls maturation of social reward circuits in the VTA.

Haploinsufficiency of SHANK3, encoding the synapse scaffolding protein SHANK3, leads to a highly penetrant form of autism spectrum disorder. How SHANK3 insufficiency affects specific neural circuits and how this is related to specific symptoms remains elusive. Here we used shRNA to model Shank3 insufficiency in the ventral tegmental area of mice. We identified dopamine (DA) and GABA cell-type-specific changes in excitatory synapse transmission that converge to reduce DA neuron activity and generate behavioral deficits, including impaired social preference. Administration of a positive allosteric modulator of the type 1 metabotropic glutamate receptors mGluR1 during the first postnatal week restored DA neuron excitatory synapse transmission and partially rescued the social preference defects, while optogenetic DA neuron stimulation was sufficient to enhance social preference. Collectively, these data reveal the contribution of impaired ventral tegmental area function to social behaviors and identify mGluR1 modulation during postnatal development as a potential treatment strategy.