Neuropsychiatric disorders affect approximately 1 in 8 people globally, stemming from a complex interplay of genetics and environment, including copy number variations like the 15q13.3 microdeletion associated with heightened risks of schizophrenia and autism. Limited medication options coupled with social, cognitive, and adaptive challenges hinder the integration of affected individuals into society due to insufficient understanding of underlying pathophysiological mechanisms. To address this, we developed a triple transgenic mouse model combining the 15q13.3+/- microdeletion with TRAP2;Ai9, facilitating the study of neuronal ensemble activation after 3-chamber social interaction paradigm (3-CSI). Our findings revealed social impairments and distinct activation patterns in somatosensory and prefrontal cortices among 15q13.3+/- mice, particularly in GABAergic neurons expressing somatostatin and parvalbumin markers, with minimal involvement of non-neuronal cells, suggesting disruption of excitation/inhibition (E/I) balance at circuit level. Future research will utilize single-nucleus RNA sequencing to identify differentially regulated genes and employ RABID-seq to map cellular connections, aiming to elucidate molecular pathways and identify precise drug targets for symptom relief and behavioral phenotype rescue associated with the microdeletion. This comprehensive approach holds promise for enhancing understanding and treatment of psychiatric conditions.