Abstract
The perirhinal cortex (PER), a region within the hippocampal memory system, is implicated in both mnemonic and perceptual functions. However, its role in emotional learning and memory remains unclear. While the PER is well established in object recognition memory, emerging evidence suggests it may also facilitate the unitization of stimulus features across modality and time in emotional tasks. Unitization refers to the binding of multiple stimulus components into a unified representation. Previous research indicates that PER inactivation via a GABA agonist impairs fear extinction training and retrieval to a discontinuous stimulus. Here, this study aimed to investigate the role of PER in stimulus unitization during the retrieval of the extinction memory. Designer receptors exclusively activated by designer drugs (DREADDs) were used to selectively silence neuronal activity in PER during fear extinction retrieval. Male Sprague-Dawley rats received bilateral PER injections of an adeno-associated virus (AAV) carrying a synthetic human muscarinic 4 receptor (hM4Gi). After a 4-week period, animals underwent a fear extinction paradigm. On day 1, Fear Acquisition, rats received five presentations of a discontinuous light (conditioned stimulus; CS) paired with a brief foot shock (unconditioned stimulus; US). On day 2, Extinction Training, rats were presented with 20 CS-alone presentations. On day 3, rats were injected intraperitoneally with either the DREADD activator (deschloroclozapine, DCZ, experimental group) or dimethyl sulfoxide (DMSO, vehicle control group). After 30 min, rats underwent Extinction Retrieval, which included 15 CS-alone presentations. Results showed no significant group differences in freezing behavior during the retrieval of the extinction memory, suggesting that PER is not required. A Spontaneous Object Recognition task confirmed that PER inactivation impaired recognition memory, validating the effectiveness of the DREADD manipulation. These findings challenge the prediction that PER is necessary for stimulus unitization during retrieval of fear extinction and instead support a temporally specific role for PER during earlier phases of fear learning. Further studies are necessary to parse apart PER contributions to the CS-US fear association compared to the CS-no US extinction association.