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Synaptic circuits associated with social interactions are affected in an autism mouse model

Social cognition is an important human skill frequently impaired in several neurodevelopmental disorders, including autism. Human genetic approaches have led to the identification of a number of genes associated with autism. However, how mutations in autism-associated genes affect the synaptic circuits of specific brain areas relevant for social interaction are not known.

To identify synaptic circuits relevant to social interaction, we have used the three-chamber social test, in which the tested mouse performs social and non-social interactions with an animated and unanimated caged-stimuli, respectively. We have modified the three-chamber test to record local field potentials (LFPs) in selected brain areas of behaving mice. Chamber modifications did not affect the behavior of the tested mice, as increased interaction of control mice with the social stimulus is preserved. Interestingly, electrophysiological recordings in control mice showed a differential pattern of activity during interaction with social versus non-social stimulus in selected brain areas of the prefrontal cortex and of the dorsal striatum. We have performed similar recordings in behaving βNrx1ΔC mice, a validated mouse model of autism that expresses a dominant negative Neurexin mutant in an inducible manner. In contrast to control mice, βNrx1ΔC mice do not show preferential interaction with the social stimulus in the three-chamber test. Notably, the electrophysiological signature induced by the interaction with the social stimulus in control mice was impaired in βNrx1ΔC mice.

Our approach allows the characterization of synaptic circuits and electrophysiological activity in brain areas during social interaction in mice and may help to understand the mechanisms responsible for autistic-like behavior. This knowledge may contribute to identify molecular mechanisms for future interventions in autism.

Local field potential recordings in behaving mice during three-chamber social test.
A. General view of the modified three-chamber apparatus.
B. Illustrative diagram and example of traces recorded from a wild-type mouse into different brain regions during social (green) vs non-social (red) interaction.