Summary Decreased hippocampal-prefrontal synchrony may mediate cognitive deficits in schizophrenia but it remains unclear which cells orchestrate this long-range synchrony. Parvalbumin- (PV) and somatostatin-expressing (SOM) interneurons show histological abnormalities in individuals with schizophrenia, and they are hypothesized to regulate oscillatory synchrony within the prefrontal cortex. To examine the relationship between interneuron function, long-range hippocampal-prefrontal synchrony, and cognition, we optogenetically inhibited SOM and PV neurons in the medial prefrontal cortex (mPFC) of mice performing a spatial working memory task while simultaneously recording neural activity in the mPFC and the hippocampus (HPC). We found that inhibiting SOM, but not PV, interneurons during the encoding phase of the task impaired working memory accuracy. This behavioral impairment was associated with decreased hippocampalprefrontal synchrony and impaired spatial encoding in mPFC neurons. These findings suggest that interneuron dysfunction may contribute to cognitive deficits associated with schizophrenia by disrupting long range synchrony between the HPC and PFC.