Investigating the impact of OPHN1 on olfactory behaviour and neuronal network dynamics

Intellectual Disability-Autism spectrum disorder (ID-ASD) are complex neurodevelopmental diseases characterized by a wide spectrum of deficits in cognitive, social and adaptive functions. Among the X-linked gene associate to ASD-ID, OPHN1 encodes a Rho GTPase-activating protein (Rho-GAP) expressed in neurons and non-neuronal cells, during development and in adulthood, in brain areas with a high degree of plasticity, such as the cortex, the hippocampus, and the olfactory bulb (OB). Several evidence indicate that part of the ID-ASD pathology can be ascribed to defects in synaptic morphology and function3-5. Most of these studies has been conducted in vitro, leaving the impact of OPHN1 mutation at systems level unaddressed. Here, we analysed the role of OPHN1 on olfactory behaviour and networks dynamics, in OPHN1-/y mice. Olfaction offers a suitable brain area to address these questions, not only because OPHN1 is here highly expressed, but also because it allows to investigate sensory and cognitive functions, both affected in ID-ASD. We found that OPHN1 exhibit impairments in an olfactory behaviour. Performing electrophysiological recordings in the OB of freely behaving OPHN1-/y mice we identified power alterations in beta and gamma bands with respect to WT controls. To analyse the organization and dynamics of neuronal population in OPHN1-/y mice, we performed two photon Ca2+ imaging. Single cell features and network organizations appeared to be severely impaired in OPHN1-/y mice with respect to controls.