Separate elements of episodic memory subserved by distinct hippocampal-prefrontal connections

Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmaco-genetic deactivation technique enabled an investigation of the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways; one arising in the dorsal CA1 (dCA1), the other in the intermediate CA1 (iCA1). While, deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was significantly different; deactivation of the dCA1→mPFC pathway selecƟvely disrupted temporal order judgements, while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a major, previously unsuspected division of function among A1 neurons that project directly to the mPFC. Such sub-networks may enable the distinctiveness of contextual information to be maintained within an episodic memory circuit.