It is widely believed that declarative memory is mediated by a medial temporal lobe memory system consisting of several distinct structures, including the hippocampus and perirhinal cortex. The strong version of this view assumes a high degree of functional homogeneity and serial organization within the medial temporal lobe, such that double dissociations between individual structures should not be possible. In the present study, we tested for a functional double dissociation between the hippocampus and peri-postrhinal cortex in a single experiment. Rats with bilateral excitotoxic lesions of either the hippocampus or peri-postrhinal cortex were assessed in tests of spatial memory (radial maze) and object recognition memory. For the latter, the spontaneous object recognition task was conducted in a modified apparatus designed to minimize the potentially confounding influence of spatial and contextual factors. A clear functional double dissociation was observed: rats with hippocampal lesions were impaired relative to controls and those with peripostrhinal cortex lesions on the spatial memory task, whereas rats with peri-postrhinal lesions were impaired relative to the hippocampal and control groups in object recognition. These results provide strong evidence in favor of heterogeneity and independence of function within the temporal lobe.

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The touchscreen testing method for rodents is a computer-automated behavioral testing method that allows computer graphic stimuli to be presented to rodents and the rodents to respond to the computer screen via a nose-poke directly to the stimulus. The advantages of this method are numerous; however, a systematic study of the parameters that affect learning has not yet been conducted. We therefore sought to optimize stimuli and task parameters in this method. We found that when parameters were optimized, Lister Hooded rats could learn rapidly using this method, solving a discrimination of two-dimensional stimuli to a level of 80% within five to six sessions lasting ∼30 min each.In a final experiment we tested both male and female rats of the albino Sprague-Dawley strain, which are often assumed to have visual abilities far too poor to be useful for studies of visual cognition. The performance of female Sprague-Dawley rats was indistinguishable from that of their male counterparts. Furthermore, performance of male Sprague-Dawley rats was indistinguishable from that of their Lister Hooded counterparts. Finally, Experiment 5 examined the ability of Lister Hooded rats to learn a discrimination between photographic stimuli. Under conditions in which parameters were optimized, rats were remarkably adept at this discrimination. Taken together, these experiments served to optimize the touchscreen method and have demonstrated its usefulness as a high-throughput method for the cognitive testing of rodents.It is now well understood that the use of animal models is an essential component in our quest to understand the brain mechanisms of cognition. In addition, such models are necessary for researchers to be able to test potential therapeutic agents in a direct and expedient manner that is not possible in human subjects. Moreover, we are experiencing a revolution in the sophistication of transgenic and knock-out animal models that creates opportunities for cognitive testing and therapeutic screening that were until recently, unthinkable (Kobayashi and Chen 2005).To achieve successful translation of findings from animal models to humans, the cognitive tasks we use with our rodents should resemble as closely as possible those used with human subjects. Increasingly, human subjects are tested using computerautomated methods. A particularly powerful approach is the "touchscreen" testing method, in which subjects respond directly to stimuli on a computer screen (e.g., Robbins et al. 1994). The advantages of this method are numerous and include facilitated performance due to contiguity between stimuli and responses and the ability to present a battery of different cognitive tests in which parameters such as stimuli, responses, and feedback are consistent across tasks and conditions.To create a cognitive testing method for rodents that matched, as far as possible, the touchscreen testing method for humans, Bussey et al. (1994Bussey et al. ( , 1997a) (see Fig. 1A) developed the touchscreen testing method for rats, a method which has...

Poor memory after brain damage is usually considered to be a result of information being lost or rendered inaccessible. It is assumed that such memory impairment must be due to the incorrect interpretation of previously encountered information as being novel. In object recognition memory experiments with rats, we found that memory impairment can take the opposite form: a tendency to treat novel experiences as familiar. This impairment could be rescued with the use of a visual-restriction procedure that reduces interference. Such a pattern of data can be explained in terms of a recent representational-hierarchical view of cognition.

De-activation of the hippocampus caused impairments in a PAL task. The selective nature of this effect (only one of the two tasks was impaired), suggests the effect is specific to cognition and cannot be attributed to gross impairments (changes in visual learning). The pattern of results suggests that rodent PAL may be suitable as a translational model of PAL in humans.

The perirhinal cortex (PRh) is widely accepted as having an important role in object recognition memory in humans and animals. Contrary to claims that PRh mediates declarative memory exclusively, previous evidence suggests that PRh has a role in the perceptual processing of complex objects. In the present study, we conducted an examination of the possible role of PRh in perceptual function in rats. We examined whether bilateral excitotoxic lesions of PRh or PPRh (perirhinal plus postrhinal cortices) in the rat would cause deficits in a zero-delay object-recognition task and a simultaneous oddity discrimination task. Both of these tasks measured spontaneous (untrained, unrewarded) behavior, and the stimuli in these experiments were manipulated to produce varying levels of perceptual difficulty. As predicted by simulations using a computational model, rats with PPRh lesions were impaired in object recognition when the stimuli to be discriminated were manipulated to share many features in common. Furthermore, rats with PPRh and PRh lesions were impaired in a simultaneous oddity discrimination task when the stimuli to be discriminated were manipulated explicitly to be more perceptually similar. These findings provide support for the idea that PRh in the rat is important for the perceptual processing of complex objects, in addition to its well established role in memory.

The hippocampus is widely considered to be a critical component of a medial temporal lobe memory system, necessary for normal performance on tests of declarative memory. Object recognition memory is thought to be a classic test of declarative memory function. However, previous tests of the effects of hippocampal lesions on object recognition memory have not always supported this view. One possible reason for this inconsistency is that previously reported effects of hippocampal lesions on object recognition memory tasks may have stemmed not from a deficit in object recognition memory per se, but as a result of spatial and contextual confounds in the task. Thus, in the present study, we used a spontaneous object recognition test in a modified apparatus designed to minimize spatial and contextual factors. A group of rats with complete excitotoxic lesions of the hippocampus and a group of control rats were tested on this modified spontaneous object recognition task with retention delays of up to 48 h. These rats were also tested on a spatial nonmatching-to-place task. Spatial memory performance was abolished following hippocampal lesions, whereas performance on the recognition memory task was intact at all delays tested.

Damage to perirhinal cortex (PRh) impairs object recognition memory in humans, monkeys, and rats when tested in tasks such as delayed nonmatching to sample, visual paired comparison, and its rodent analog, the spontaneous object recognition task. In the present study, we have capitalized on the discrete one-trial nature of the spontaneous object recognition task to investigate the role of PRh in several distinct stages of object recognition memory. In a series of experiments, transient inactivation of PRh was accomplished with bilateral infusions of lidocaine directly into PRh immediately before the sample phase (encoding), immediately before the choice phase (retrieval), or within the retention delay after the sample phase (storage-consolidation). Compared with performance on trials in which they received saline infusions, rats were significantly impaired when lidocaine was infused before the sample phase, regardless of the length of the retention delay. Similarly, delay-independent deficits were observed after immediate pre-choice infusions of lidocaine. Finally, PRh inactivation immediately and 20 min after the sample phase, but not 40, 60, or 80 min after, also disrupted subsequent object recognition when the retention delay was sufficiently long to ensure the dissipation of the actions of lidocaine during the choice phase. The effects of pre-sample and pre-choice inactivation indicate involvement of PRh in encoding and retrieval stages of object recognition, and the time course of post-sample inactivation effects suggests a role for PRh in the maintenance of the object trace during memory consolidation.