Severe anxiety frequently co-occurs with core symptoms of autism spectrum disorders (ASD); however, the determinants are unexplored (Kerns et al., 2021). One of the most reliable anomalies reported in both ASD and anxiety disorder patients is an aberrant functional connectivity between the salience network and the default mode network (Uddin et al., 2015). Our data indicate that a specific inhibitory neuronal subpopulation plays a fundamental role in salience detection and in gating sensory stimuli to adaptively shape behavior. The aim of the project is to test whether failure in the encoding of salience by altered neuronal subpopulation functionality in ASD leads to altered processing of sensory stimuli, contributing to anxiety and ASD symptomatology. We generated a mouse line with a selective deletion of an ASD-related gene in our target population. Behavioral batteries are used to test if these animals display typical ASD-like dysfunctions and anxiety. Furthermore, we use dual-color Ca2+ imaging to investigate the altered functionality of the specific inhibitory neuronal subpopulation. Thus far, our investigations have revealed an absence of deficits in the tested ASD-related behaviors, including hyperlocomotion, spatial memory, compulsive behavior and social preference. However, alterations in anxiety-like behavior have been observed in female mice as assessed using an approach/avoidance-based test, namely the elevated plus maze. In conclusion, the selective deletion of an ASD associated gene within the specific neuronal subpopulation induces dysfunctions in anxiety-like behaviors. Further investigations regarding the potential of the subpopulation as a key player in anxiety and ASD are currently underway.