Absence of parvalbumin results in an Autism Spectrum Disorder-like phenotype in mice

Autism spectrum disorder (ASD) patients are characterized by impairments in social interaction, communication and stereotyped patterns of behavior, interests, and activities. ASD-associated genes often encode proteins that are implicated in synaptic transmission and/or structure. Functionally these changes result in an impairment of neurotransmission at individual synapses and at the network level, in modifications of e.g. the excitation/inhibition (E/I) balance that might be caused by mutations in ASD risk genes during earlier steps in neurodevelopment. Within the global neuronal network, interneurons play a key role in the maintenance of the overall balance of activity and interneuron dysfunctions are linked with cognitive impairment in neuropsychiatric disorders. In particular, the number of fast-spiking interneurons (FSI) expressing the calcium-binding protein parvalbumin (PV) has been reported to be decreased in different well-assessed mouse models of ASD. PV-deficient mice (PV-/and PV+/-) show ASD-like symptoms similar to ones reported in other “canonical” ASD mouse models (Wöhr et al., 2015). According to the current view, the decrease in PV-immunoreactive (PV-ir) neurons in mouse ASD models is the result of a “loss” of PV-expressing FSI, leading to a change in the E/I balance.