Reduced theta-band transfer entropy from vHPC to mPFC in MCAO mice with novel object recognition memory impairment

Ischemic stroke is a leading cause of cognitive impairment, notably affecting object recognition memory. At the neural circuit level, the ventral hippocampus (vHPC)-medial prefrontal cortex (mPFC) pathway is essential for encoding novel object recognition memory. While studies in healthy animals indicate that successful recognition is associated with enhanced theta oscillatory coupling between the vHPC and mPFC, the information flow between circuit remains unclear. Moreover, whether and how ischemic stroke alters this dynamic circuit interaction, thereby contributing to memory impairment, is still unknown. To address this, we investigated whether ischemic injury disrupts theta oscillatory activity and directional information transfer within the vHPC-mPFC circuit, using a mouse model of middle cerebral artery occlusion (MCAO). We combined novel object recognition (NOR) testing with in vivo multichannel electrophysiology to record local field potentials from the vHPC and mPFC during task performance. Directional information transfer was assessed using amplitude transfer entropy. Behaviorally, MCAO mice showed significantly reduced novel object discrimination compared with controls. Neural oscillations revealed that theta power in both regions during novel object exploration was markedly lower in MCAO mice. Furthermore, theta-band directional analysis identified vHPC → mPFC as the predominant information flow pathway, and its strength was significantly weakened after ischemia. These results demonstrate that MCAO-induced recognition memory impairment is closely linked to dysfunction of theta-band directional information transfer from the vHPC to the mPFC. Our study provides new insights into the circuit mechanisms underlying cognitive deficits after stroke.