PV+ optogenetic stimulations at specific frequencies in specific brain regions can restore navigational flexibility in an acute MK801 mouse model of schizophrenia

Impairments of decision-making and behavioral flexibility in schizophrenia (SCZ) are currently the most investigated features. One convincing hypothesis explaining this cognitive impairment is the excitatory/inhibitory (E/I) ratio imbalance in brain regions such as the medial prefrontal cortex (mPFC) and the ventral hippocampus (vHPC). An increased GLUergic excitatory activity and a decreased GABAergic inhibitory activity induces an mPFC-vHPC {gamma}/{theta} band desynchronization in many tasks testing behavioral flexibility. However, these tasks were carried out using "perceptual" decision-making/flexibility but not navigational decision-making/flexibility. Our study addressed the role of frequency-specific optogenetic stimulations of GABAergic parvalbumin-positive (PV+) interneurons in mPFC (50Hz, {gamma}-like) and vHPC (10Hz, {theta}-like) in an acute-MK801 mouse model of navigational inflexibility. We used the active place avoidance task on a rotating arena. Results showed that frequency-specific optogenetic stimulations of mPFC or vHPC acted differently in restoring navigational flexibility, advancing our knowledge of the pivotal role of PV+ activity in SCZ-like navigational decision-making/flexibility.