Perirhinal and postrhinal cortices are necessary for retrieving latently-acquired stimulus associations

The perirhinal and postrhinal cortices reside in the parahippocampal region of the medial temporal lobe. They receive and process sensory information from cortical and subcortical sources and support hippocampal functions via direct connectivity and indirectly via the entorhinal cortex. Previous studies using the sensory preconditioning paradigm have shown that the perirhinal and postrhinal cortices are necessary for associating cues during preconditioning and retrieving the associations during conditioning. However, the question of whether these regions are also required for stimulus association retrieval during re-exposure to the preconditioning cue had not been addressed. Using a chemogenetic approach, we temporarily suppressed the perirhinal or postrhinal cortex in adult male rats during the preconditioning cue test phase. Both suppression groups showed impaired sensory preconditioning compared to sham surgery controls, as indicated by significantly reduced preferential responding. Implications of our findings are discussed in relation to the importance of the PER and POR in context processing and episodic-like memory in animal models. Significance statementAlthough Pavlovian conditioning between two stimuli is widely used in neuroscience, associative learning in the real-world is often too complex to be modeled by first-order conditioning alone. Proper responding may require integrating multiple associations via common elements, i.e. higher-order conditioning, the neural basis of which is not well understood. Whereas existing research indicates the perirhinal and postrhinal cortices in the medial temporal lobe contribute to certain forms of sensory preconditioning (SPC, a type of higher-order conditioning), we suggest their contributions lie in the encoding and retrieving latently acquired associations, processes which are central to all forms of SPC. We argue this interpretation also captures perirhinal and postrhinal contributions to contextual and episodic memory, hence offering a unifying explanation regarding the contributions of these cortices across multiple paradigms.