A platform to investigate social behaviour in physiological and pathological conditions: neuronal network dynamics in the olfactory bulb and prefrontal cortex in response to social odorant stimuli

This thesis investigated social behavior in both physiological and pathological conditions by examining behavior and neuronal network dynamics in the olfactory bulb (OB) and prefrontal cortex (PFC) in response to odorant stimuli in mice. Odors, particularly amines, which are volatile compounds found in biological fluids such as urine, are known to elicit both attractive and aversive behaviors (Liberles, 2015). Amines, which bind to a distinct class of receptors, the Trace Amine-Associated Receptors (TAARs), in the main olfactory bulb, have been associated with innate behaviors that are believed to be controlled by subcortical areas such as the amygdala and hypothalamus (Liberles, 2015). However, whether and how amines are processed in higher brain areas involved in social cognitive functions, such as the prefrontal cortex (PFC), remains unclear. In this work, we addressed this open question by performing behavioral tests and recordings from the OB and PFC. Specifically, we optimized a three-chamber task and recorded local field potentials (LFPs) in the OB and PFC of head-restrained mice. Using this modified three-chamber task, we found that wild-type (WT) mice showed a clear preference for TMA, as expected. In contrast, OPHN1 mutant mice, a model of intellectual disability (ID) and autism spectrum disorder (ASD), displayed no such preference, suggesting impairments in processing socially relevant cues. Recordings of LFPs in the OB and PFC of head-restrained mice revealed distinct neural responses to different odors, depending on the mice's genotype. Both WT and mutant mice showed an increase in the OB, in beta oscillations, which are associated with odor processing, in response to all odorant stimuli, regardless of their social valence. However, when comparing the beta power increase between genotypes, we found a statistically significant difference between WT and mutant mice only for socially relevant stimuli. In the PFC, we observed a clear increase in beta power exclusively in mutant mice. Coherence between brain areas is crucial for effective communication (Fries, 2005). To assess this, we calculated the coherence between OB and PFC and found higher correlated activity in mutant mice, but only in response to social odorants. Altogether, our results establish a platform for detecting behavioral and neural network differences in response to social stimuli between WT and mutant animals. Notably, we demonstrated that amines are processed in the PFC, and we identified distinct differences in both behavior and network dynamics between WT and mutant mice.