Juan M.J. Ramos

The perirhinal cortex and long-term spatial memory in rats.

Two experiments examined the effects of perirhinal cortex and hippocampal neurotoxic lesions on the retention of allocentric information. Perirhinal (Expt. 1) and hippocampal rats (Expt. 2) were trained on an allocentric task until they reached a performance equal to that of the control groups. Results showed that 24 days after acquisition, during a retraining period, only the hippocampal rats presented a deficit in retention. These results suggest that the perirhinal cortex and the hippocampus can be functionally dissociated in terms of their participation in the formation of long-term spatial memory. Also, the allocentric spatial memory functions of the hippocampus seem not to depend on their afferent connections with the perirhinal cortex.

Preserved learning about allocentric cues but impaired flexible memory expression in rats with hippocampal lesions.

Several studies have shown that slight modifications in the standard reference spatial memory procedure normally used for allocentric learning in the Morris water maze and the radial maze, can overcome the classic deficit in allocentric navigation typically observed in rats with hippocampal damage. In these special paradigms, however, there is only intramaze manipulation of a salient stimulus. The present study was designed to investigate whether extramaze manipulations produce a similar outcome. With this aim a four-arm plus-shaped maze and a reference spatial memory paradigm were used, in which the goal arm was marked in two ways: by a prominent extramaze cue (intermittent light), which maintained a constant relation with the goal, and by the extramaze constellation of stimuli around the maze. Experiment 1 showed that, unlike the standard version of the task, using this special training procedure hippocampally-damaged rats could learn a place response as quickly as control animals; importantly, one day after reaching criterion, lesioned and control subjects performed the task perfectly during a transfer test in which the salient extramaze stimulus used during the acquisition was removed. However, although acquisition deficit was overcomed in these lesioned animals, a profound deficit in retention was detected 15 days later. Experiment 2 suggests that although under our special paradigm hippocampal rats can learn a place response, spatial memory only can be expressed when the requisites of behavioral flexibility are minimal. These findings suggest that, under certain circumstances, extrahippocampal structures are sufficient for building a coherent allocentric representation of space; however, flexible memory expression is dependent, fundamentally, on hippocampal functioning.

Differential contribution of hippocampus, perirhinal cortex and postrhinal cortex to allocentric spatial memory in the radial maze

Rats with hippocampal, perirhinal cortex and postrhinal cortex lesions were trained in a reference spatial memory task to determine whether these structures contribute differentially to the acquisition and retention of spatial information. The results of Experiment 1 indicated that hippocampal lesions profoundly impaired the acquisition of the task. However, postrhinal lesions produced only a mild deficit and perirhinal lesions produced no deficit whatsoever in the learning of the task. During acquisition, hippocampus-damaged rats committed more perseverative errors than postrhinal rats, suggesting that the nature of the operations performed by each of these structures is different. The results of Experiment 2 showed a profound deficit in retention in hippocampal and postrhinal-lesioned animals tested 24 days after training. Perirhinal-lesioned animals, however, executed the task just as well as the control subjects did. These functional data, in consonance with existing connectivity data, suggest that each of these medial temporal lobe regions makes a different contribution to allocentric spatial learning and memory.

Essential Role of the Perirhinal Cortex in Complex Tactual Discrimination Tasks in Rats

We designed a battery of tactual discrimination tasks to study whether rats with perirhinal cortex (Prh) lesions had any deficit in resolving complex/ambiguous tactual tasks in the dark. Animals had to discriminate among 3 stimuli simultaneously exposed in 3 arms of a 4-arm plus-shaped maze. Rats with Prh lesions showed a profound impairment in a texture discrimination learning task when the stimuli had a high or intermediate degree of feature ambiguity (experiments 1a and 1b), but not when they had a low degree of feature ambiguity (experiment. 1c). Hippocampal lesions, however, did not cause any impairment in task acquisition even when the stimuli had a high degree of feature ambiguity (experiment 2). Experiments 3a, 3b, and 4 showed that perirhinal and control rats performed the task similarly when the animals had to discriminate on the basis of simple/individual, nonoverlapping features of the stimuli (size) with different levels of difficulty. Finally, to isolate the tasks memory functions from its perceptual functions, a reversal learning task revealed a profound deficit in the initial learning phase, but unimpaired learning in the reversal phase with identical stimuli (experiment 5). The findings suggest that the Prh plays an essential role in somatosensory perceptual functions.

Peripheral pathways mediating salivary secretion after nucleus parvocellularis activation in the rat

The present study demonstrates that activation of the nucleus parvocellularis in the pontine reticular formation of the rat evokes salivary hypersecretion. The secretory effect observed was found to be mediated by parasympathetic mechanisms, as transection of the preganglionic parasympathetic salivatory fibers at the level of the middle ear blocked the flow of saliva evoked by activation of the nucleus parvocellularis (Experiment 1). Furthermore, transection of these salivatory fibers was followed several days later by the development of a prandial model of drinking. These behavioral data suggest that the transection procedure employed in the present study indeed affected those parasympathetic fibers which control the secretory activity of all three pairs of major salivary glands (Experiment 2).

Submandibular and parotid salivary secretion after electrolytic lesioning of the brainstem nucleus parvocellularis in the rat

The present study, in consonance with recent anatomical investigations, demonstrates that activation of the nucleus parvocellularis in the rat evokes a potent hypersecretory effect in the submandibular and sublingual (S-S) salivary glands. Furthermore, electrolytic lesioning of this region in conjunction with peripheral removal of the parotid glands is followed by an increase in the number of drinking responses in the presence of dry food. Such prandial drinking behavior is only observed after total impairment of salivation (i.e., removal of the S-S + parotid glands), thus suggesting that the parvocellularis lesion led to a marked deficit in S-S salivary secretion. On the other hand, the activation of the nucleus parvocellularis was seen to have only a slight effect on parotid salivary secretion. Electrolytic lesions to this zone, when associated with peripheral removal of the S-S glands, failed to induce prandiality, suggesting that the parvocellularis nucleus exerted a low level of control over parotid salivary secretion. These results are interpreted as functional proof of the relationship between the parvocellularis reticular formation and the superior salivatory nucleus in the secretion of S-S saliva.

The perirhinal cortex of the rat is necessary for spatial memory retention long after but not soon after learning

Many observations in humans and experimental animals support the view that the hippocampus is critical immediately after learning in order for long-term memory formation to take place. However, exactly when the medial temporal cortices adjacent to the hippocampus are necessary for this process to occur normally is not yet well known. Using a spatial task, we studied whether the perirhinal cortex of rats is necessary to establish representations in long-term memory. Results showed that, in a spatial task sensitive to hippocampal lesions, control and perirhinal lesioned rats can both learn at the same rate (Experiment 1). Interestingly, a differential involvement of the perirhinal cortex in memory retention was observed as time passes after learning. Thus, 24 days following the end of learning, lesioned and control rats remembered the task perfectly as measured by a retraining test. In contrast, 74 days after the learning the perirhinal animals showed a profound impairment in the retention of the spatial information (Experiment 2). Taken together, these results suggest that the perirhinal region is critical for the formation of long-term spatial memory. However, its contribution to memory formation and retention is time-dependent, it being necessary only long after learning takes place and not during the phase immediately following acquisition.

The nucleus parvocellularis reticularis regulates submandibular-sublingual salivary secretion in the rat: a pharmacological study.

This experiment shows that activation of the nucleus parvocellularis reticularis in the rat brainstem provokes salivary hypersecretion by the submandibular-sublingual glands. The secretory effect is mediated by cholinergic mechanisms, as the administration of atropine blocked the flow of saliva evoked by stimulation of the nucleus parvocellularis. In contrast, injection of dihydroergotamine (an alpha-blocker) and/or propranolol (a beta-blocker) failed to significantly reduce submandibular and sublingual salivary secretion when compared to a control group injected with distilled water. The cholinergic nature of the salivary response suggests that the nucleus parvocellularis reticularis exerts its secretory effect on the salivary glands parasympathetically rather than through mechanisms associated with sympathetic pathways. The area of the brainstem activated in the present study closely overlaps the region in which cell bodies of superior salivatory neurons have recently been identified with retrograde transport of peroxidase. The data presented herein represent functional proof in support of the location of the superior salivatory nucleus within the parvocellularis reticular formation.

Rats with hippocampal lesions can learn a place response, but how long can they retain it?

Previous research has shown that electrolytic hippocampal lesions do not affect the acquisition of a place response if a special training procedure is used. However, 24 days later, the hippocampal rats manifest a profound deficit in the retention of the spatial information (J. M. J. Ramos, 2000). The goal of the present study was, therefore, to investigate how long the hippocampal rats can retain a place response. Results showed that, 3 days after the end of the training, lesioned rats remembered as well as the control rats, but this was no longer true 6 or 12 days after the training. This retention deficit was not observed when the spatial information was acquired by means of a guidance strategy. These results suggest that, when a special training procedure is used, the hippocampus is not necessary for the learning of a place task but is required for the formation of long-term spatial memory.

Hippocampal damage impairs long-term spatial memory in rats : Comparison between electrolytic and neurotoxic lesions

In previous studies we have suggested that the dorsal hippocampus is involved in spatial consolidation by showing that rats with electrolytic hippocampal lesions exhibit a profound deficit in the retention of an allocentric task 24 days after the acquisition. However, in various hippocampal-dependent tasks, several studies have shown an overestimation of the behavioral deficit when electrolytic versus axon-sparing cytotoxic lesions has been used. For this reason, in this report we compare the effects on spatial retention of electrolytic and neurotoxic lesions to the dorsal hippocampus. Results showed a similar deficit in spatial retention in both groups 24 days after acquisition. Thus, the hippocampus proper and not fibers of passage or extrahippocampal damage is directly responsible for the deficit in spatial retention seen in rats with electrolytic lesions.