SUMMARYExpression of the immediate-early gene c-fos was used to test for different patterns of temporal lobe interactions when rats explore either novel or familiar objects. A new behavioural test of recognition memory was first devised to generate robust levels of novelty discrimination and to provide a matched control condition using familiar objects. Increased c-Fos activity was found in caudal, but not rostral portions, of perirhinal cortex (areas 35/36) and in area Te2 in rats showing object recognition i.e. preferential exploration of novel versus familiar objects. The findings are presented at a higher anatomical resolution than previous studies of immediate-early gene expression and object novelty and, crucially, provide the first analyses when animals are actively discriminating the novel objects. Novel versus familiar object comparisons also revealed altered cFos patterns in hippocampal subfields, with relative increases in CA3 and CA1 and decreases in the dentate gyrus. These hippocampal changes match those previously reported for the automatic coding of object-spatial associations. Additional analyses of the c-Fos data using structural equation modelling indicated the presence of pathways starting in the caudal perirhinal cortex that display a direction of effects from the entorhinal cortex to the CA1 field (temporo-ammonic) when presented with familiar objects, but switch to the engagement of the direct entorhinal cortex pathway to the dentate gyrus (perforant) with novel object discrimination. This entorhinal switch provides a potential route by which the rhinal cortex can moderate hippocampal processing, with a dynamic change from temporo-ammonic (familiar stimuli) to perforant pathway (novel stimuli) influences.

The present study examines 2 factors that might moderate the object-recognition deficit seen after perirhinal cortex damage. Object recognition by normal rats was improved by extending (from 4 to 8 min) the sample period during which an object was first explored. Furthermore, there was a significant positive correlation between time spent in close exploration of the sample object and degree of successful novelty discrimination. In contrast, rats with perirhinal cortex lesions failed to benefit from increased close exploration and did not discriminate the novel object after even the longest sample period. Nevertheless, the lesions did not disrupt habituation across repeated exposure to the same object. The second factor was extent of perirhinal cortex damage. A significant correlation was found between total perirhinal cortex loss and degree of recognition impairment. Within the perirhinal cortex, only damage to the caudal perirhinal cortex correlated significantly with recognition memory deficits. This study highlights the critical importance of the perirhinal cortex within the temporal lobe for recognition memory and shows that the lesion-induced deficit occurs despite seemingly normal levels of close object exploration.

Animals often show an innate preference for novelty. This preference facilitates spontaneous exploration tasks of novelty discrimination (recognition memory). In response to limitations with standard spontaneous object recognition procedures for rodents, a new task ("bow-tie maze") was devised. This task combines features of delayed nonmatching-to-sample with spontaneous exploration. The present study explored aspects of object recognition in the bow-tie maze not amenable to standard procedures. Two rat strains (Lister Hooded, Dark Agouti) displayed very reliable object recognition in both the light and dark, with the Lister Hooded strain showing superior performance (Experiment 1). These findings reveal the potential contribution of tactile and odor cues in object recognition. As the bow-tie maze task permits multiple trials within a session, it was possible to derive forgetting curves both within-session and between-sessions (Experiment 1). In Experiment 2, rats with hippocampal or fornix lesions performed at normal levels on the basic version of the recognition task, contrasting with the marked deficits previously seen after perirhinal cortex lesions. Next, the training protocol was adapted (Experiment 3), and this modified version was used successfully with mice (Experiment 4). The overall findings demonstrate the efficacy of this new behavioral task and advance our understanding of object recognition.

The medial diencephalon is vital for memory, but it is not known why. The present study tested between the predictions of current hypotheses as to why this region is critical for memory. Lesions were made in the rat mammillothalamic tract, the only diencephalic structure consistently associated with amnesia in humans after ischemia. Decreased activity, as measured by immediate-early gene expression (c-fos), was found in three key sites associated with memory function: the hippocampus, the prefrontal cortex, and the retrosplenial cortex. The specificity of these changes was confirmed by the qualitatively different patterns of immediately-early gene changes seen after amygdala lesions, e.g., hypoactivity in the hippocampus and retrosplenial cortex following mammillothalamic tract lesions but not following amygdala lesions. The mammillothalamic lesion results unify substrates linked to diencephalic and temporal lobe amnesia, and thereby support a new account of diencephalic amnesia that emphasizes multiple dysfunctions across hippocampal, retrosplenial, and prefrontal areas. This account suggests a role for the mammillary bodies that is independent of their hippocampal inputs.

Rats with perirhinal cortex lesions were sequentially trained in a rectangular water tank on a series of 3 visual discriminations, each between mirror-imaged stimuli. When these same discriminations were tested concurrently, the rats were forced to use a configural strategy to solve the problems effectively. There was no evidence that lesions of the perirhinal cortex disrupted the ability to learn the concurrent configural discrimination task, which required the rats to learn the precise combination of stimulus identity with stimulus placement (“structural” learning). The same rats with perirhinal cortex lesions were also unimpaired on a test of spatial working memory (reinforced T maze alternation), although they were markedly impaired on a new test of spontaneous object recognition. For the recognition test, rats received multiple trials within a single session in which on every trial, they were allowed to explore 2 objects, 1 familiar, the other novel. On the basis of their differential exploration times, rats with perirhinal cortex lesions showed very poor discrimination of the novel objects, thereby confirming the effectiveness of the surgery. The discovery that bilateral lesions of the perirhinal cortex can leave configural (structural) learning seemingly unaffected points to a need to refine those models of perirhinal cortex function that emphasize its role in representing conjunctions of stimulus features.