Synapsins are a family of synaptic vesicle phosphoproteins (SVs) playing a key role in synaptic transmission and neuronal development. Mutations of Syn genes lead to dysregulation in brain network functions implicated in the pathophysiology of neurological and psychiatric disorders. We aimed at investigating the impact of deletion of all three Syn isoforms on social and cognitive behavior in Syn triple knockout (TKO) mice and on the neuronal activity of the glutamatergic transmission in the infralimbic medial prefrontal cortex (IL-mPFC) and in hippocampal CA3 using in vivo electrophysiology. A set of behavioral tests included T-maze test, marble test (MB), social discrimination test (SDC), stereotyped repetitive behaviors and five-trial social memory test (5-TSM). Single unit extracellular recordings measured the spontaneous electrical activity of glutamatergic pyramidal neurons in IL- mPFC and CA3. TKO exhibited social impairment, interacting for a significantly reduced time with the novel mouse compared to the WT (p<0.001) in the sociability test. A significant increase in the number (p<0.0001), duration of grooming behavior and a significant decrease in latency (p<0.05) was observed in TKO in contrast to rearing behavior where a significant decrease in the number (p<0.05) and in the duration (p<0.01) was measured. A significant reduction in firing rate was also detected in the IL-mPFC (p<0.05) of TKO mice. Our results suggest that the deletion of all three Syn genes in mice leads to reduction in firing activity of pyramidal neurons in the IL-mPFC, along with social and cognitive dysfunctions.