The basolateral amygdala complex and perirhinal cortex represent focal and peripheral states of information processing in rats

We previously identified the roles of the basolateral amygdala complex (BLA) and perirhinal cortex (PRh) in sensory preconditioning in male and female rats (Wong et al., 2025). Here, we used variations of a sensory preconditioning protocol to test a general theory that the BLA and PRh represent focal and peripheral states of attention, respectively. We specifically tested predictions derived from the theory regarding when learning about a stimulus that signals danger will be disrupted by BLA or PRh infusions of the N-methyl-D-aspartate receptor (NMDAR) antagonist, DAP5. Consistent with the theory, the effects of these infusions depended on the novelty/familiarity of the conditioned stimulus, as well as the manner in which it was paired with foot shock. When a stimulus was novel, its conditioning required NMDAR-activation in the BLA and not the PRh, regardless of whether the stimulus and shock were presented contiguously or separated in time. When a pre-exposed and, thereby, familiar stimulus was presented contiguously with shock, its conditioning again required NMDAR-activation in the BLA and not the PRh. However, when a pre-exposed stimulus was indirectly paired with shock - because it was associatively activated at the time of shock or separated from the shock by another stimulus - its conditioning required NMDAR-activation in the PRh and not the BLA. These findings are discussed in relation to theories of information processing that distinguish between focal and peripheral states of attention/memory, and past studies that have examined the substrates of learning and memory in the PRh and BLA.

This study examined the effect of danger on consolidation of neutral information in two regions of the rat (male and female) medial temporal lobe: the perirhinal cortex (PRh) and basolateral amygdala complex (BLA). The neutral information was the association that forms between an auditory stimulus and a visual stimulus (labeled S2 and S1) across their pairings in sensory preconditioning. We show that, when the sensory preconditioning session is followed by a shocked context exposure, the danger shifts consolidation of the S2-S1 association from the PRh to the BLA; and does so by interacting with processes involved in encoding of the S2-S1 pairings. Specifically, we show that the initial S2-S1 pairing in sensory preconditioning is encoded in the BLA and not the PRh; whereas the later S2-S1 pairings are encoded in the PRh and not the BLA. When the sensory preconditioning session is followed by a context alone exposure, the BLA-dependent trace of the early S2-S1 pairings decays and the PRh-dependent trace of the later S2-S1 pairings is consolidated in memory. However, when the sensory preconditioning session is followed by a shocked context exposure, the PRh-dependent trace of the later S2-S1 pairings is suppressed and the BLA-dependent trace of the initial S2-S1 pairing is consolidated in memory. These findings are discussed with respect to mutually inhibitory interactions between the PRh and BLA, and the way that these regions support memory in other protocols, including recognition memory in people.SIGNIFICANCE STATEMENT The perirhinal cortex (PRh) and basolateral amygdala complex (BLA) process the pairings of neutral auditory and visual stimuli in sensory preconditioning. The involvement of each region in this processing is determined by the novelty/familiarity of the stimuli as well as events that occur immediately after the preconditioning session. Novel stimuli are represented in the BLA; however, as these stimuli are repeatedly presented without consequence, they come to be represented in the PRh. Whether the BLA- or PRh-dependent representation is consolidated in memory depends on what happens next. When nothing of significance occurs, the PRh-dependent representation is consolidated and the BLA-dependent representation decays; but when danger is encountered, the PRh-dependent representation is inhibited and the BLA-dependent representation is selected for consolidation.

The Long and the Short of It: Memory Signals in the Medial Temporal Lobe

Recent research suggests that the medial temporal lobe (MTL) is involved in perception as well as in declarative memory. Amnesic patients with focal MTL lesions and semantic dementia patients showed perceptual deficits when discriminating faces and objects. Interestingly, these two patient groups showed different profiles of impairment for familiar and unfamiliar stimuli. For MTL amnesics, the use of familiar relative to unfamiliar stimuli improved discrimination performance. By contrast, patients with semantic dementia—a neurodegenerative condition associated with anterolateral temporal lobe damage—showed no such facilitation from familiar stimuli. Given that the two patient groups had highly overlapping patterns of damage to the perirhinal cortex, hippocampus, and temporal pole, the neuroanatomical substrates underlying their performance discrepancy were unclear. Here, we addressed this question with a multivariate reanalysis of the data presented by Barense et al. (2011), using functional connectivity to examine how stimulus familiarity affected the broader networks with which the perirhinal cortex, hippocampus, and temporal poles interact. In this study, healthy participants were scanned while they performed an odd-one-out perceptual task involving familiar and novel faces or objects. Seed-based analyses revealed that functional connectivity of the right perirhinal cortex and right anterior hippocampus was modulated by the degree of stimulus familiarity. For familiar relative to unfamiliar faces and objects, both right perirhinal cortex and right anterior hippocampus showed enhanced functional correlations with anterior/lateral temporal cortex, temporal pole, and medial/lateral parietal cortex. These findings suggest that in order to benefit from stimulus familiarity, it is necessary to engage not only the perirhinal cortex and hippocampus, but also a network of regions known to represent semantic information.

ABSTRACTThere is much evidence that the perirhinal cortex of both rats and monkeys is important for judging the relative familiarity of visual stimuli. In monkeys many studies have found that a proportion of perirhinal neurons respond more to novel than familiar stimuli. There are fewer studies of perirhinal neuronal responses in rats, and those studies based on exploration of objects, have raised into question the encoding of stimulus familiarity by rat perirhinal neurons. For this reason, recordings of single neuronal activity were made from the perirhinal cortex of rats so as to compare responsiveness to novel and familiar stimuli in two different behavioral situations. The first situation was based upon that used in “paired viewing” experiments that have established rat perirhinal differences in immediate early gene expression for novel and familiar visual stimuli displayed on computer monitors. The second situation was similar to that used in the spontaneous object recognition test that has been widely used to establish the involvement of rat perirhinal cortex in familiarity discrimination. In the first condition 30 (25%) of 120 perirhinal neurons were visually responsive; of these responsive neurons 19 (63%) responded significantly differently to novel and familiar stimuli. In the second condition eight (53%) of 15 perirhinal neurons changed activity significantly in the vicinity of objects (had “object fields”); however, for none (0%) of these was there a significant activity change related to the familiarity of an object, an incidence significantly lower than for the first condition. Possible reasons for the difference are discussed. It is argued that the failure to find recognition‐related neuronal responses while exploring objects is related to its detectability by the measures used, rather than the absence of all such signals in perirhinal cortex. Indeed, as shown by the results, such signals are found when a different methodology is used. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

Much evidence indicates that recognition memory involves two separable processes, recollection and familiarity discrimination, with familiarity discrimination being dependent on the perirhinal cortex of the temporal lobe. Here, we describe a new neural network model designed to mimic the response patterns of perirhinal neurons that signal information concerning the novelty or familiarity of stimuli. The model achieves very fast and accurate familiarity discrimination while employing biologically plausible parameters and Hebbian learning rules. The fact that the activity patterns of the model's simulated neurons are closely similar to those of neurons recorded from the primate perirhinal cortex indicates that this brain region could discriminate familiarity using principles akin to those of the model. If so, the capacity of the model establishes that the perirhinal cortex alone may discriminate the familiarity of many more stimuli than current neural network models indicate could be recalled (recollected) by all the remaining areas of the cerebral cortex. This efficiency and speed of detecting novelty provides an evolutionary advantage, thereby providing a reason for the existence of a familiarity discrimination network in addition to networks used for recollection.

This study used variations of a sensory preconditioning protocol in male and female rats to test a theory that the basolateral amygdala complex (BLA) and perirhinal cortex (PRh) represent focal and peripheral states of attention, respectively. It specifically tested predictions derived from the theory regarding when learning about a stimulus that signals danger will be disrupted by BLA or PRh infusions of the N-methyl-D-aspartate receptor (NMDAR) antagonist, DAP5. Consistent with the theory, the effects of these infusions depended on the novelty/familiarity of the conditioned stimulus as well as the manner in which it was paired with foot shock. When a stimulus was novel, its conditioning required activation of NMDAR in the BLA and not the PRh (Experiments 2A and 2B) regardless of whether the stimulus-shock pairings were contiguous or separated in time. When a pre-exposed and, thereby, familiar stimulus was presented contiguously with shock, its conditioning again required activation of NMDAR in the BLA and not the PRh (Experiments 1A, 1B, 3A and 3B). However, when a pre-exposed stimulus was indirectly paired with shock - because it was associatively activated at the time of shock or separated from the shock by another stimulus - its conditioning required activation of NMDAR in the PRh and not the BLA (Experiments 1A, 1B, 3A and 3B). These findings are discussed in relation to theories of information processing that distinguish between focal and peripheral states of attention/memory, and past studies that have examined the substrates of learning and memory in the PRh and BLA.

This study used variations of a sensory preconditioning protocol in male and female rats to test a theory that the basolateral amygdala complex (BLA) and perirhinal cortex (PRh) represent focal and peripheral states of attention, respectively. It specifically tested predictions derived from the theory regarding when learning about a stimulus that signals danger will be disrupted by BLA or PRh infusions of the N-methyl-D-aspartate receptor (NMDAR) antagonist, DAP5. Consistent with the theory, the effects of these infusions depended on the novelty/familiarity of the conditioned stimulus as well as the manner in which it was paired with foot shock. When a stimulus was novel, its conditioning required activation of NMDAR in the BLA and not the PRh (Experiments 2A and 2B) regardless of whether the stimulus-shock pairings were contiguous or separated in time. When a pre-exposed and, thereby, familiar stimulus was presented contiguously with shock, its conditioning again required activation of NMDAR in the BLA and not the PRh (Experiments 1A, 1B, 3A and 3B). However, when a pre-exposed stimulus was indirectly paired with shock - because it was associatively activated at the time of shock or separated from the shock by another stimulus - its conditioning required activation of NMDAR in the PRh and not the BLA (Experiments 1A, 1B, 3A and 3B). These findings are discussed in relation to theories of information processing that distinguish between focal and peripheral states of attention/memory, and past studies that have examined the substrates of learning and memory in the PRh and BLA.

This study used variations of a sensory preconditioning protocol in male and female rats to test a theory that the basolateral amygdala complex (BLA) and perirhinal cortex (PRh) represent focal and peripheral states of attention, respectively. It specifically tested predictions derived from the theory regarding when learning about a stimulus that signals danger will be disrupted by BLA or PRh infusions of the N-methyl-D-aspartate receptor (NMDAR) antagonist, DAP5. Consistent with the theory, the effects of these infusions depended on the novelty/familiarity of the conditioned stimulus as well as the manner in which it was paired with foot shock. When a stimulus was novel, its conditioning required activation of NMDAR in the BLA and not the PRh (Experiments 2A and 2B) regardless of whether the stimulus-shock pairings were contiguous or separated in time. When a pre-exposed and, thereby, familiar stimulus was presented contiguously with shock, its conditioning again required activation of NMDAR in the BLA and not the PRh (Experiments 1A, 1B, 3A and 3B). However, when a pre-exposed stimulus was indirectly paired with shock - because it was associatively activated at the time of shock or separated from the shock by another stimulus - its conditioning required activation of NMDAR in the PRh and not the BLA (Experiments 1A, 1B, 3A and 3B). These findings are discussed in relation to theories of information processing that distinguish between focal and peripheral states of attention/memory, and past studies that have examined the substrates of learning and memory in the PRh and BLA.

This study used variations of a sensory preconditioning protocol in male and female rats to test a theory that the basolateral amygdala complex (BLA) and perirhinal cortex (PRh) represent focal and peripheral states of attention, respectively. It specifically tested predictions derived from the theory regarding when learning about a stimulus that signals danger will be disrupted by BLA or PRh infusions of the N-methyl-D-aspartate receptor (NMDAR) antagonist, DAP5. Consistent with the theory, the effects of these infusions depended on the novelty/familiarity of the conditioned stimulus as well as the manner in which it was paired with foot shock. When a stimulus was novel, its conditioning required activation of NMDAR in the BLA and not the PRh (Experiments 2A and 2B) regardless of whether the stimulus-shock pairings were contiguous or separated in time. When a pre-exposed and, thereby, familiar stimulus was presented contiguously with shock, its conditioning again required activation of NMDAR in the BLA and not the PRh (Experiments 1A, 1B, 3A and 3B). However, when a pre-exposed stimulus was indirectly paired with shock - because it was associatively activated at the time of shock or separated from the shock by another stimulus - its conditioning required activation of NMDAR in the PRh and not the BLA (Experiments 1A, 1B, 3A and 3B). These findings are discussed in relation to theories of information processing that distinguish between focal and peripheral states of attention/memory, and past studies that have examined the substrates of learning and memory in the PRh and BLA.

This study used variations of a sensory preconditioning protocol in male and female rats to test a theory that the basolateral amygdala complex (BLA) and perirhinal cortex (PRh) represent focal and peripheral states of attention, respectively. It specifically tested predictions derived from the theory regarding when learning about a stimulus that signals danger will be disrupted by BLA or PRh infusions of the N-methyl-D-aspartate receptor (NMDAR) antagonist, DAP5. Consistent with the theory, the effects of these infusions depended on the novelty/familiarity of the conditioned stimulus as well as the manner in which it was paired with foot shock. When a stimulus was novel, its conditioning required activation of NMDAR in the BLA and not the PRh (Experiments 2A and 2B) regardless of whether the stimulus-shock pairings were contiguous or separated in time. When a pre-exposed and, thereby, familiar stimulus was presented contiguously with shock, its conditioning again required activation of NMDAR in the BLA and not the PRh (Experiments 1A, 1B, 3A and 3B). However, when a pre-exposed stimulus was indirectly paired with shock - because it was associatively activated at the time of shock or separated from the shock by another stimulus - its conditioning required activation of NMDAR in the PRh and not the BLA (Experiments 1A, 1B, 3A and 3B). These findings are discussed in relation to theories of information processing that distinguish between focal and peripheral states of attention/memory, and past studies that have examined the substrates of learning and memory in the PRh and BLA.

This study used variations of a sensory preconditioning protocol in male and female rats to test a theory that the basolateral amygdala complex (BLA) and perirhinal cortex (PRh) represent focal and peripheral states of attention, respectively. It specifically tested predictions derived from the theory regarding when learning about a stimulus that signals danger will be disrupted by BLA or PRh infusions of the N-methyl-D-aspartate receptor (NMDAR) antagonist, DAP5. Consistent with the theory, the effects of these infusions depended on the novelty/familiarity of the conditioned stimulus as well as the manner in which it was paired with foot shock. When a stimulus was novel, its conditioning required activation of NMDAR in the BLA and not the PRh (Experiments 2A and 2B) regardless of whether the stimulus-shock pairings were contiguous or separated in time. When a pre-exposed and, thereby, familiar stimulus was presented contiguously with shock, its conditioning again required activation of NMDAR in the BLA and not the PRh (Experiments 1A, 1B, 3A and 3B). However, when a pre-exposed stimulus was indirectly paired with shock - because it was associatively activated at the time of shock or separated from the shock by another stimulus - its conditioning required activation of NMDAR in the PRh and not the BLA (Experiments 1A, 1B, 3A and 3B). These findings are discussed in relation to theories of information processing that distinguish between focal and peripheral states of attention/memory, and past studies that have examined the substrates of learning and memory in the PRh and BLA.

This study used variations of a sensory preconditioning protocol in male and female rats to test a theory that the basolateral amygdala complex (BLA) and perirhinal cortex (PRh) represent focal and peripheral states of attention, respectively. It specifically tested predictions derived from the theory regarding when learning about a stimulus that signals danger will be disrupted by BLA or PRh infusions of the N-methyl-D-aspartate receptor (NMDAR) antagonist, DAP5. Consistent with the theory, the effects of these infusions depended on the novelty/familiarity of the conditioned stimulus as well as the manner in which it was paired with foot shock. When a stimulus was novel, its conditioning required activation of NMDAR in the BLA and not the PRh (Experiments 2A and 2B) regardless of whether the stimulus-shock pairings were contiguous or separated in time. When a pre-exposed and, thereby, familiar stimulus was presented contiguously with shock, its conditioning again required activation of NMDAR in the BLA and not the PRh (Experiments 1A, 1B, 3A and 3B). However, when a pre-exposed stimulus was indirectly paired with shock - because it was associatively activated at the time of shock or separated from the shock by another stimulus - its conditioning required activation of NMDAR in the PRh and not the BLA (Experiments 1A, 1B, 3A and 3B). These findings are discussed in relation to theories of information processing that distinguish between focal and peripheral states of attention/memory, and past studies that have examined the substrates of learning and memory in the PRh and BLA.

Previous work has shown that immunohistochemical imaging of Fos protein is a reliable marker for changes in activity related to recognition memory in the perirhinal (PRH) cortex of the medial temporal lobe; however, whether PRH Fos expression is necessary for recognition memory had not been established. To investigate this potential requirement, antisense Fos oligodeoxynucleotide (ODN) was infused locally into PRH cortex to interfere with Fos production. As in previous studies, differential Fos expression produced by viewing novel or familiar visual stimuli was measured by immunohistochemistry: antisense Fos ODN infusion into PRH cortex disrupted the normal pattern of differential Fos expression in PRH cortex. The effect of antisense Fos ODN infusion into PRH cortex was therefore sought on recognition memory. Infusion before or immediately after acquisition impaired recognition memory for objects when the memory delay was 3 or 24 h, but not when the delay was 20 min, or when the ODN was infused before retrieval after a 24-h delay. The findings indicate a role for Fos in consolidation processes underlying long-term recognition memory for objects and establish that interfering with its expression impairs recognition memory. Antisense Fos ODN infusion also impaired object-in-place recognition memory. The results demonstrate that Fos is necessary for neuronal mechanisms in PRH cortex essential to recognition memory.

The present study examined immediate-early gene expression in the perirhinal cortex of rats with hippocampal lesions. The goal was to test those models of recognition memory which assume that the perirhinal cortex can function independently of the hippocampus. The c-fos gene was targeted, as its expression in the perirhinal cortex is strongly associated with recognition memory. Four groups of rats were examined. Rats with hippocampal lesions and their surgical controls were given either a recognition memory task (novel vs. familiar objects) or a relative recency task (objects with differing degrees of familiarity). Perirhinal Fos expression in the hippocampal-lesioned groups correlated with both recognition and recency performance. The hippocampal lesions, however, had no apparent effect on overall levels of perirhinal or entorhinal cortex c-fos expression in response to novel objects, with only restricted effects being seen in the recency condition. Network analyses showed that whereas the patterns of parahippocampal interactions were differentially affected by novel or familiar objects, these correlated networks were not altered by hippocampal lesions. Additional analyses in control rats revealed two modes of correlated medial temporal activation. Novel stimuli recruited the pathway from the lateral entorhinal cortex (cortical layer II or III) to hippocampal field CA3, and thence to CA1. Familiar stimuli recruited the direct pathway from the lateral entorhinal cortex (principally layer III) to CA1. The present findings not only reveal the independence from the hippocampus of some perirhinal systems associated with recognition memory, but also show how novel stimuli engage hippocampal subfields in qualitatively different ways from familiar stimuli.