Integrins are biomechanical receptors that connect both physically and functionally the extracellular matrix (ECM) to the intracellular cytoskeleton, regulating synaptic connectivity and plasticity in response to extracellular cues. In particular, in the brain, β3 integrin interacts with the αV subunit to form the αVβ3 integrin heterodimer, which mediates adhesion strengthening of excitatory synapses in cortical pyramidal neurons.Alteration in integrin structure, expression or signalling is involved in the aetiology of various brain pathologies, including autism spectrum disorder (ASD) and epilepsy, two comorbid brain disorders. Specifically, β3 integrin haplo-insufficiency impairs network excitability and synchrony of cortical neuronal networks.We developed a CRISPRa technology to fine-tune the synaptic expression of endogenous β3 integrin as a rescue strategy to modulate cortical activity.Using mechanogenetic approaches coupled with behavioral analyses, we investigate how the modulation of β3 integrin expression influences cortical synaptic transmission and mice behavior. Our results provide insights on how β3 integrin regulates social behaviour. Targeting this mechanoreceptor could offer new possibilities for developing new therapeutic strategies for ASD and related forms of epilepsy.