What pharmacological interventions indicate concerning the role of the perirhinal cortex in recognition memory

Abstract

Findings of pharmacological studies that have investigated the involvement of specific regions of the brain in recognition memory are reviewed. The particular emphasis of the review concerns what such studies indicate concerning the role of the perirhinal cortex in recognition memory. Most of the studies involve rats and most have investigated recognition memory for objects. Pharmacological studies provide a large body of evidence supporting the essential role of the perirhinal cortex in the acquisition, consolidation and retrieval of object recognition memory. Such studies provide increasingly detailed evidence concerning both the neurotransmitter systems and the underlying intracellular mechanisms involved in recognition memory processes. They have provided evidence in support of synaptic weakening as a major synaptic plastic process within perirhinal cortex underlying object recognition memory. They have also supplied confirmatory evidence that that there is more than one synaptic plastic process involved. The demonstrated necessity to long-term recognition memory of intracellular signalling mechanisms related to synaptic modification within perirhinal cortex establishes a central role for the region in the information storage underlying such memory. Perirhinal cortex is thereby established as an information storage site rather than solely a processing station. Pharmacological studies have also supplied new evidence concerning the detailed roles of other regions, including the hippocampus and the medial prefrontal cortex in different types of recognition memory tasks that include a spatial or temporal component. In so doing, they have also further defined the contribution of perirhinal cortex to such tasks. To date it appears that the contribution of perirhinal cortex to associative and temporal order memory reflects that in simple object recognition memory, namely that perirhinal cortex provides information concerning objects and their prior occurrence (novelty/familiarity).

Fig. 1

Schematic diagram of four object recognition memory tasks. (A) Novel object preference task (OR), (B) object location task (OL), (C) object-in-place task (OiP) and (D) temporal order task (TO).

Fig. 2

Schematic representation of different patterns of response reduction on stimulus repetition. There are three patterns of neuronal response reduction found on repetition of novel and highly familiar visual stimuli found in monkey anterior inferior temporal cortex, including the perirhinal cortex. Neurons with ‘recency responses’ signal that a stimulus has been seen recently by a reduced response to that stimulus, but do not signal whether it is unfamiliar or highly familiar, because the response to both types of stimulus is the same. ‘Familiarity responses’ signal that a stimulus is highly familiar (has been seen many times on previous days) by a reduced response to such a stimulus but do not signal that a stimulus has been seen recently (within the past several minutes), because the responses to its first and second occurrence are the same. ‘Novelty responses’ signal that the stimulus is being seen for the first time by a vigorous response that is much weaker when the stimulus is repeated and much briefer (thinner bar) if the stimulus is highly familiar. (After Fig. 17 of Brown & Xiang (1998); reproduced with permission).

Fig. 3

Neuronal memory spans. (A) Responses averaged across populations of novelty, recency and familiarity neurons recorded in anterior inferior temporal cortex in the monkey. The mean response (% of background activity) to novel stimuli is shown in by the first bar (‘N’). Subsequent bars give the mean response to repeat presentations after the indicated number of intervening trials (0–64) or after a 24 h delay. Note that for novelty and recency neurons the response to repeat presentations is reduced and that the magnitude of the reduction decreases as the intervening interval increases (‘forgetting curve’). In contrast, for familiarity neurons there is no significant reduction at short intervals but then the reduction increases with interval. ^⁎ Difference from response to novel, p<0.05. (B) The proportion of neurons with reduced response on stimulus repetition where the reduction was still significant after a 24 h interval between initial and subsequent presentation. Data are shown for novelty, recency and familiarity neurons in anterior visual association cortex (TE), perirhinal cortex (PRH) and entorhinal cortex (ENT). Note the high proportion of familiarity neurons with memory spans of ≥24 h. Data from Xiang & Brown (1998).

Fig. 4

Differential memory decays (forgetting curves) produced by selective glutamatergic and cholinergic antagonists. The curves follow the ‘forgetting curves’ of the different neuronal types – novelty and recency (N) compared to familiarity (F) – as shown in Fig. 3A. If kainate (KAR) and muscarinic receptor antagonists target ‘novelty’ and ‘recency’ (fast synaptic change) neurons, while NMDA and nicotinic receptor antagonists target ‘familiarity’ (slow synaptic change) neurons, then the different forgetting curves provide potential explanation for the different amnesic effects observed: NMDA or muscarinic antagonism results in short-term memory followed by forgetting at longer intervals, whereas kainate (KAR) or muscarinic antagonism produces short-term forgetting followed by long-term remembrance.

Fig. 5

Schematic representation of connections within the perirhinal–hippocampal–medial prefrontal circuit involved in object-in-place and temporal order memory.