Parotid hypersalivation after inferior salivatory nucleus glutamate/NMDA receptor excitation in the rat.

Although salivation is essential during eating behavior, little is known about the brainstem centers that directly control the salivary glands. With regard to the inferior salivatory nucleus (ISN), the site of origin of the parasympathetic preganglionic cell bodies that innervate the parotid glands, previous anatomical studies have located it within the rostrodorsal medullary reticular formation. However, to date there is no functional data that shows the secretory nature of the somas grouped in this region. To activate only the somas and rule out the activation of the efferent fibers from and the afferent fibers to the ISN, in exp. 1, NMDA neurotoxin was administered to the rostrodorsal medullary region and the secretion of saliva was recorded during the following hour. Results showed an increased secretion of parotid saliva but a total absence of submandibular-sublingual secretion. In exp. 2, results showed that the hypersecretion of parotid saliva after NMDA microinjection was completely blocked by the administration of atropine (a cholinergic blocker) but not after administration of dihydroergotamine plus propranolol (α and ß-adrenergic blockers, respectively). These findings suggest that the somata of the rostrodorsal medulla are secretory in nature, controlling parotid secretion via a cholinergic pathway. The data thus functionally supports the idea that these cells constitute the ISN.

Microinjection of NMDA-neurotoxin into the superior salivatory nucleus of the rat: Short-term secretory and long-term drinking behavior effects.

The anatomical location of the superior salivatory nucleus (SSN), the site of origin of the parasympathetic preganglionic cell bodies that innervate the submandibular-sublingual salivary glands, is well established in rats. However, as of yet there is no functional data that convincingly shows the secretory nature of this region. Previous studies have not been able to differentiate between interventions on efferent or afferent fibers connected to the SSN versus interventions on the salivatory nucleus itself. Taking advantage of the fact that salivatory neurons express NMDA-receptors on their somas, in the present study SSN cell bodies were activated and lesioned sequentially by means of intracerebral application of NMDA-neurotoxin. In exp. 1 two effects, a short- and a long-term effect, were observed following NMDA administration. The first effect was high submandibular-sublingual saliva secretion during the hour following administration of the neurotoxin and the second was a profound change in drinking behavior once the animals recovered from the lesion. Thus, on post-surgery days 16, 17 and 18, the rats exhibited hyperdipsia in the presence of dry food but not in the presence of wet food. In expt. 2 results showed that saliva hypersecretion observed after NMDA-microinjection was completely blocked by the administration of atropine (a cholinergic blocker) but not after the administration of dihydroergotamine plus propranolol (α and ß-adrenergic blockers, respectively). From a functional perspective, these data suggest that the somata of the parvocellular reticular formation control the secretory activity of the submandibular-sublingual salivary glands and thus constitute the SSN.

Rapid decay of spatial memory acquired in rats with ventral hippocampus lesions.

Several memory consolidation theories have proposed that following a learning situation the hippocampus gradually stabilizes labile recent memories into long-lasting remote memories. Most work in this field has focused on the dorsal hippocampus (DHip), giving little consideration to a possible contribution by the ventral hippocampus (VHip), particularly when spatial paradigms are used. However, in recent years a growing number of studies have suggested the existence of a functional continuum, related to spatial processing and navigation, along the dorsoventral hippocampal axis. For this reason, in the present study we compare the effect of DHip vs. VHip lesions on long-term spatial memory retention. Using a four-arm plus-shaped maze, rats with lesions in the DHip, VHip or sham-lesioned learned to criterion a place discrimination task based on allothetic cues. During two retraining phases (2 days and 24 days after learning) retention of the spatial information learned during the acquisition phase was evaluated. The main findings revealed no deficit 2 days after learning, but 24 days after learning both lesioned groups showed a profound impairment compared to control animals (expt. 1). In contrast, when rats learned a cue-guided navigation task in the acquisition phase, both lesioned groups performed the two retention tests, 2 days and 24 days after learning, at the same level as the control group (expt. 2). These results suggest not only that the DHip is vital, but also that normal VHip activity is critical during the post-learning period in order for a recent spatial memory to become a stable long-term memory.

Ventral hippocampus lesions and allocentric spatial memory in the radial maze: Anterograde and retrograde deficits.

Although the dorsal hippocampus (DHip) has been clearly implicated in spatial learning and memory, there is currently debate as to whether the ventral hippocampus (VHip) is also necessary in allocentric-based navigation tasks. To differentiate between these two subregions of the hippocampal dorsoventral axis, we examined the effect of neurotoxic lesions to the DHip and VHip in different learning situations, using a four-arm plus-shaped maze. In experiment 1 a spatial reference memory task was used, with results showing an acquisition deficit in DHip-lesioned rats but perfect learning in VHip-lesioned rats. However, in experiment 2 an acquisition deficit was found in VHip-lesioned rats using a doubly marked training protocol. In this case the position of the goal arm during training was marked simultaneously by the extramaze constellation of stimuli around the maze and an intramaze cue. The main results indicated that DHip and VHip groups presented significantly more allocentric errors in the probe test than the control rats. In experiments 3 and 4, animals with their brains still intact learned, respectively, a spatial reference memory task or a purely cue-guided navigation task, and DHip and VHip lesions were made 2-3 days after reaching learning criterion. Results indicated a profound retrograde deficit in both lesioned groups but only with regard to allocentric information. So, depending on the training protocol used, our results point to increased integration and cooperation throughout the hippocampal dorsoventral axis when allocentric learning and memory is involved. These data support the existence of a functional continuum from the dorsal to the ventral hippocampus.

Disconnection of the perirhinal and insular cortices severely disrupts taste neophobia.

It is well known that the perirhinal (Prh) and insular (IC) cortices are reciprocally connected, mainly through ipsilateral projections. Although some studies have demonstrated that excitotoxic lesions to these regions, each separately, disrupt taste neophobia, it is not yet known whether the two regions have functional interactions with one another. To find out if they form a functional unit, we examined the effects of crossed excitotoxic lesions to the Prh and the contralateral IC (contralateral group). This group's performance was compared to that of rats with ipsilateral Prh and IC lesions (ipsilateral group) and to that of control-operated rats. All the animals received a 0.3% saccharin solution for fifteen minutes on five consecutive days. Rats with contralateral Prh-IC lesions drank significantly higher amounts of saccharin than the other groups during the first encounter with the novel taste, indicating a disruption in neophobia. However, the lesions did not disrupt attenuation of neophobia, with the contralateral group reaching asymptote in trial 2 and the rest of the groups after 3-5 days of exposure to the saccharin. These findings suggest that both Prh and IC play a necessary role in taste neophobia. Additionally, the two cortices function interdependently and their interaction is critical for normal expression of taste neophobia.

Perirhinal cortex supports both taste neophobia and its attenuation.

Rats are often reluctant to consume novel tastes because they lack knowledge about the postingestive effects the new foods might have. This paper examines the effect of excitotoxic lesions and temporary inactivation of the perirhinal cortex (Prh), a key region in the recognition memory system, on taste neophobia and its attenuation. Using a two-bottle choice paradigm (saccharin vs water), excitotoxic lesions were found to disrupt taste neophobia to 0.3% and 0.5% saccharin. However, the lesions had no effect when using a concentration of 0.7%, which is qualitatively aversive (expt. 1a-1c). In a second series of experiments the same animals were able to acquire a flavor preference learning on the basis of a flavor-taste association. Lesioned and control rats showed, during a choice test, a clear preference for the flavor associated with saccharin (expt. 2a-2c). Finally, in a third series of experiments, Prh inactivation with lidocaine after trial 1 (expt. 3) and after trials 1-3 (expt. 4) delayed attenuation of the neophobia. These findings suggest that Prh lesions do not significantly affect taste processing/ perception. Prh thus appears to play an essential role in taste neophobia and its attenuation.

RELATIONSHIP between prandial drinking behavior and supersensitivity of salivary glands after superior salivatory nucleus lesions in RATS.

Prandial drinking, an increase in the number of drinking responses and secondary or non-homeostatic polydipsia in the presence of dry food, is typically associated with a deficit in salivary secretion. This study investigates the degree of salivary gland supersensitivity to pilocarpine administration after lesions to the superior salivatory nucleus (SSN), the site of origin of the parasympathetic preganglionic neurons that innervate the submandibular-sublingual (S-S) salivary glands. The main aim was to determine if there is a relationship between the degree of glandular supersensitivity, as an index of secretory deficit, and the development of prandial drinking in lesioned rats. Results showed that following SSN lesions two subgroups of rats were obtained. One subgroup exhibited prandial drinking but the other was similar to the control group. The SSN-lesioned prandial drinking subgroup presented significantly greater supersensitivity than the SSN-lesioned non-prandial drinking rats; the non-prandial drinking subgroup, in turn, presented significantly more supersensitivity than controls. Additionally, S-S supersensitivity observed in rats that exhibited prandial drinking due to the sectioning of chorda tympani efferent axons was compared to that observed in rats exhibiting prandial drinking due to SSN lesions. It was found that both groups presented the same S-S supersensitivity curve. These results indicate that SSN lesions produce a gradation of S-S supersensitivity values that appear to run parallel to the degree of glandular secretory deficit caused by the lesions. Thus, only the rats with greater secretory deficit (greater supersensitivity) develop prandial drinking. These data support the idea that there is in fact a functional link between the lateral reticular formation of the brainstem (the region associated with the SSN) and S-S salivary glands.

Perirhinal cortex involvement in allocentric spatial learning in the rat: Evidence from doubly marked tasks.

It has recently been suggested that the different cortices of the medial temporal lobe support a mixture of object and spatial processing functions, challenging the anterior model that emphasized a strict functional differentiation between regions. However, for some structures, the perirhinal cortex (Prh) for example, a number of studies using lesion methods have shown a profound deficit exclusively in tasks involving object learning but not allocentric spatial learning. It may be that the learning paradigms used in previous studies have not been sensitive enough to detect a possible allocentric deficit in Prh-lesioned animals. To examine whether Prh lesions critically affect allocentric spatial learning, experimental and control rats were trained in two doubly marked navigation tasks. In experiment 1, the use of either one of two different memory systems, allocentric versus egocentric, made it possible to locate the goal arm in a four-arm radial maze. In experiment 2, rats had to choose between an allocentric versus a S-R/habit strategy, both of which predicted the location of the goal arm. Results showed that both experimental and control animals learned both navigation tasks well, reaching the same level of performance at the end of training. However, a probe test performed 1 day after the learning ended revealed that Prh-damaged animals learned both tasks predominantly using a non-allocentric strategy. Specifically, in lesioned subjects the percentage of egocentric correct responses (experiment 1) and the percentage of habit-based correct responses (experiment 2) was significantly higher than in the control rats. On the other hand, in both experiments, control rats in the probe test presented a significantly higher number of allocentric correct responses than the lesioned subjects. These results clearly suggest that Prh is normally needed for using allocentric strategies in order to solve a navigation problem. © 2017 Wiley Periodicals, Inc.

Perirhinal cortex supports tactual discrimination tasks with increasing levels of complexity: Retrograde effect.

Recent studies have suggested that the perirhinal cortex (Prh) supports representations of feature conjunctions in the visual modality during the acquisition/encoding of complex discriminations. To extend this idea to other sensory modalities and to another stage of the discrimination process, we studied the effect of Prh lesions on the expression of a series of tactual discrimination tasks learned preoperatively. These tasks differed from one another in the degree of feature overlap of the stimuli and in the difficulty of the task. During pre- and post-operative testing phases, rats had to discriminate among 3 stimuli simultaneously exposed in 3 arms of a 4-arm plus-shaped maze. Prh-damaged rats showed a profound impairment in the expression of tactual discrimination tasks when the stimuli had a high or intermediate degree of feature ambiguity, but not when they had a low degree of ambiguity (experiments 1a-1c). In order to experimentally dissociate between subregions within the medial temporal lobe, experiment 2 was conducted to show that hippocampal lesions did not cause any impairment in task expression even when the stimuli had a high degree of feature ambiguity. When the tactual discrimination tasks used simple/individual nonoverlapping features of the stimuli (size), Prh lesions did not affect the expression of these discriminations despite the high level of difficulty of these tasks (experiments 3a and 3b). These findings suggest that, in the somatosensory modality, the Prh plays an essential role in the processing of complex stimuli with overlapping features but not in simple tactual discriminations. Furthermore, the Prh is necessary not just during acquisition but also during expression/performance of the discrimination task.

Differential contribution of perirhinal cortex and hippocampus to taste neophobia: effect of neurotoxic lesions.

Although the perirhinal cortex (Prh) has been extensively related to recognition memory, little is known about its specific role in taste memories. The main aim of the present series was therefore to examine the effect of neurotoxic lesions of the Prh on taste neophobia, a phenomenon consisting of a low intake of a novel food until its postingestive consequences are determined. The results showed that Prh-lesioned rats consumed significantly more novel saccharin in trial 1 than control subjects when a saccharin solution of 0.3% (expt. 1a) and 0.5% (expt. 1b) was presented. However, when the saccharin concentration was high and qualitatively more aversive, Prh lesions did not affect the neophobic response (0.7%, expt. 1c) and the lesioned and control animals consumed a similar amount of the fluid during the first and subsequent test trials. In all three experiments, Prh-lesioned and control rats showed a comparable intake at asymptote. Experiment 2 and 3 showed that neurotoxic lesions to the dorsal hippocampus prior to or 24h after the intake of the novel taste (0.3% saccharin) had no effect on the initial occurrence of the neophobic response or on the consolidation of safe taste memory, respectively. These findings support a dissociation of functions between the Prh and the hippocampus in taste neophobia. Also, the data suggests that the Prh plays an essential role in detecting the novelty of the new tastant.

Perirhinal cortex lesions attenuate stimulus generalization in a tactual discrimination task in rats.

Response generalization to a novel stimulus occurs when the new stimulus shares common features with the stimulus used in the original learning. Given the many recent studies suggesting that the perirhinal cortex is critical for disambiguating stimuli that share representational/perceptual elements, we hypothesize that lesions sustained to this region would attenuate response generalization. In the first part of this experiment lesioned and control rats learned a feature-ambiguous tactual discrimination task until they had all reached the same level of performance. In this task animals were asked to discriminate among 3 tactual stimuli simultaneously exposed in 3 arms of a 4-arm plus-shaped maze. In the second part of this experiment, the same rats were given a generalization test 24 h after acquisition of the tactual discrimination. In the generalization test the original tactual stimulus associated with reward during the learning of the discrimination was replaced by a novel tactual stimulus while the other two remained the same. Of the 3 stimuli used in the generalization test, the novel stimulus had the highest degree of feature overlap with respect to the original target stimulus used during the learning of the discrimination. The generalization test took place over two consecutive days, with 8 trials each day. On the first day of generalization, the results indicated that the lesioned rats generalized significantly worse than the control rats during the first 4 trials, but not during the last 4 trials. On the second day of generalization, however, both groups performed the test perfectly. These findings suggest that, in addition to the well-known mnesic function in object processing, the perirhinal cortex may also be involved in perceptual functions.

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 task's 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.

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.

Profound retrograde but absence of anterograde amnesia for cued place learning in rats with hippocampal lesions.

Previous studies in our lab have shown that slight modifications in the spatial reference memory procedure can overcome the deficit in spatial learning typically observed in rats with hippocampal damage. However, it is unknown if memory acquired under such training circumstances is spared after hippocampal lesions. With this aim a four-arm plus-shaped maze and a spatial reference memory paradigm were used, in which the goal arm was doubly marked: by an intramaze cue (a piece of sandpaper positioned on the floor of the arm) and by the extramaze constellation of stimuli around the maze. Experiment 1 replicated previous findings showing that hippocampally damaged rats can learn a place response just as well as the controls when the intramaze cue is present during the training, but they are unable to do so in the absence of the intramaze signal. When the learning procedure was doubly signaled, a transfer test performed 24h after the end of acquisition demonstrated that lesioned rats showed perfect memory for the goal arm when the intramaze cue was removed. Experiment 2 investigated the effect of hippocampal damage 1 day after the learning. Results showed that regardless of the training procedure employed (with or without the intramaze cue), hippocampal lesions produced a profound retrograde amnesia. Thus, although the absence of anterograde amnesia suggests that structures other that the hippocampus can take charge of the acquisition, the presence of retrograde amnesia indicates the critical role of the normal hippocampus in the long-term formation of allocentric information.

Perirhinal cortex lesions produce retrograde but not anterograde amnesia for allocentric spatial information: within-subjects examination.

Using a reference spatial memory task sensitive to hippocampal lesions, the same groups of rats were subjected to four successive experimental phases to investigate which aspects of spatial cognition are perirhinal cortex dependent. Results showed that the perirhinal cortex is not necessary for acquisition or for long-term spatial memory retention. However, the perirhinal cortex was differentially involved in spatial memory expression depending on whether the original learning took place in an intact brain or in a perirhinal damaged brain. Specifically, only when the lesions were made after learning was a profound impairment in the expression of preoperatively acquired spatial information observed. These results suggest that, in a normal brain, the perirhinal cortex plays an essential role in the expression of spatial information during the post-learning period.

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.

Remote spatial memory and the hippocampus: effect of early and extensive training in the radial maze.

In a previous study we showed a temporally graded retrograde amnesia after hippocampal lesions when rats learned a spatial reference memory task in which two types of signals simultaneously indicated the goal arm (shape of the experimental room and extramaze landmarks). To investigate the effect that the navigational demands of the task have on remote memory expression, the same task was used in the present study as in our previous report, but on this occasion the shape of the surroundings was not predictive, which resulted in a highly demanding spatial task. Additionally, animals received extensive training in an early phase to ensure that the task was well learned. Results indicated a profound retrograde amnesia when dorsal hippocampal lesions were made 1 or 70 d after the end of the training (experiments 1 and 2). Using a long period of retraining, however, lesioned animals in the 70-d groups showed progressively more spared memory than the lesioned rats of the 1-d group. Experiments 3 and 4 showed that rats did not learn the above spatial task through an S-R association. Specifically, when animals acquired the task using a single cue (intra- or extramaze), hippocampal lesions did not produce retrograde amnesia. These findings support the possibility that in a highly demanding spatial task, hippocampal lesions produce a performance/navigational impairment that could interfere with the expression of spared remote spatial memory. The long period of retraining, however, seems to partially compensate for this deficit, but only when a long learning-surgery interval is employed.

Is spatial memory transformed during the consolidation process? Effect of reminding.

Several studies in rats have shown activation of cortical regions and concurrent deactivation of the hippocampus during the retrieval of spatial memory, as the consolidation process progresses. To determine whether during this post-learning period of memory reorganization, spatial memories are transformed from a specific to a more generic representation, in Experiment 1 we compare remote spatial memory measured using a single probe trial versus relearning. Results show that spatial memory can be effectively retrieved using a single probe trial during the 18 days following learning; after this time a retraining procedure is necessary. In Experiment 2 and 3 we tested the effect of a reminder treatment on the retrieval of remote memory. Results indicate that when the reminder was applied after experimental day 18, the treatment did not significantly improve the retrieval of spatial memory during a retention test (Exp. 2); however, if the reminder was applied before day 18, a significant improvement during the retention test was observed (Exp. 3). In order to investigate the extent to which memory becomes more difficult to retrieve as time passes due specifically to a retrieval deficit, in experiment 4 no significant differences, but marginal ones, were detected between an overtrained group and a control group when the retention test took place 30 days after the end of learning. Overall, the present results suggest that as the consolidation process progresses, spatial information becomes more difficult to recover, in part because the original detailed trace has gradually been transformed into a more schematic representation.

Perirhinal cortex lesions produce retrograde amnesia for spatial information in rats: consolidation or retrieval?

Several lines of evidence in humans and experimental animals suggest that the hippocampus is critical for the formation and retrieval of spatial memory. However, although the hippocampus is reciprocally connected to adjacent cortices within the medial temporal lobe and they, in turn, are connected to the neocortex, little is known regarding the function of these cortices in memory. Here, using a reference spatial memory task in the radial maze, we show that neurotoxic perirhinal cortex lesions produce a profound retrograde amnesia when learning-surgery intervals of 1 or 50 d are used (Experiment 1). With the aim of dissociating between consolidation and retrieval processes, we injected lidocaine either daily after training (Experiment 2) or before a retention test once the learning had been completed (Experiment 3). Results show that reversible perirhinal inactivation impairs retrieval but not consolidation. However, the same procedure followed in Experiment 2 disrupted consolidation when the lidocaine was injected into the dorsal hippocampus. The results of Experiment 4 rule out the possibility that the deficit in retrieval is due to a state-dependent effect. These findings demonstrate the differential contribution of various regions of the medial temporal lobe to memory, suggesting that the perirhinal cortex plays a key role in the retrieval of spatial information for a long period of time.

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.