Social recognition in laboratory mice requires integration of behaviorally-induced somatosensory, auditory and olfactory cues.

In humans, discrimination between individuals, also termed social recognition, can rely on a single sensory modality, such as vision. By analogy, social recognition in rodents is thought to be based upon olfaction. Here, we hypothesized that social recognition in rodents relies upon integration of olfactory, auditory and somatosensory cues, hence requiring active behavior of social stimuli. Using distinct social recognition tests, we demonstrated that adult male mice do not exhibit recognition of familiar stimuli or learn the identity of novel stimuli that are inactive due to anesthesia. We further revealed that impairing the olfactory, somatosensory or auditory systems prevents behavioral recognition of familiar stimuli. Finally, we found that familiar and novel stimuli generate distinct movement patterns during social discrimination and that subjects react differentially to the movement of these stimuli. Thus, unlike what occurs in humans, social recognition in mice relies on integration of information from several sensory modalities.

Pharmacological modulation of AMPA receptors rescues specific impairments in social behavior associated with the A350V Iqsec2 mutation.

In this study we tested the hypothesis that pharmacological modulation of glutamatergic neurotransmission could rescue behavioral deficits exhibited by mice carrying a specific mutation in the Iqsec2 gene. The IQSEC2 protein plays a key role in glutamatergic synapses and mutations in the IQSEC2 gene are a frequent cause of neurodevelopmental disorders. We have recently reported on the molecular pathophysiology of one such mutation A350V and demonstrated that this mutation downregulates AMPA type glutamatergic receptors (AMPAR) in A350V mice. Here we sought to identify behavioral deficits in A350V mice and hypothesized that we could rescue these deficits by PF-4778574, a positive AMPAR modulator. Using a battery of social behavioral tasks, we found that A350V Iqsec2 mice exhibit specific deficits in sex preference and emotional state preference behaviors as well as in vocalizations when encountering a female mouse. The social discrimination deficits, but not the impaired vocalization, were rescued with a single dose of PF-4778574. We conclude that social behavior deficits associated with the A350V Iqsec2 mutation may be rescued by enhancing AMPAR mediated synaptic transmission.