Hippocampectomized Rats Research Articles

Home bases formed to visual cues but not to self‐movement (dead reckoning) cues in exploring hippocampectomized rats

Spatial theory proposes that the hippocampus contributes to exploratory behavior allowing animals to acquire information about their environment. In the present study, the exploratory movements of control rats, bulbectomized (anosmic) rats and hippocampectomized rats using the neurotoxin N-methyl-D-aspartate (NMDA) were monitored on a large circular table without walls and around which visual cues were manipulated. The rats displayed organized spatial behavior in that they developed home bases, one or more places operationally defined as those in which they spent a preponderance of time, in which they moved slowly, and to which they returned after excursions. Control rats and hippocampectomized rats were similar in that they established home bases: (i) adjacent to a proximal stable or moving visual landmark; (ii) in relation to more distant visual room cues; and (iii) in relation to contextually conditioned visual cues. Nevertheless, in exploratory tests given under infrared light, a wavelength to which rats are insensitive, control rats and bulbectomized rats established one or more home bases that were not dependent upon surface (e.g. olfactory) cues, whereas home base behavior was absent/fragmented in hippocampectomized rats. Thus, exploratory behavior, as exemplified by home base behavior, is organized in control and hippocampectomized rats in relation to visual cues, but is not organized in hippocampectomized rats when visual cues are absent. This result is discussed in relation to the idea that the hippocampus contributes to spatial behavior that is dependent upon guidance (dead reckoning) derived from self-movement cues.

Psychoemotional manifestations in hippocampectomized rats

The effects of lesioning of the dorsal hippocampus on the psychoemotional state of Wistar rats were studied. Hippocampal lesions did not affect the learning process, but affected mainly the pattern of psychoemotional manifestations in all animals regardless of the typology of higher nervous activity. All animals showed reductions in the extremes of types of passive and active stress reactions. Individual effects depended on the behavioral phenotypes of the animals. Hippocampal lesions in rapidly learning rats (10%) led to sharp decreases in irritability (active/passive = 0.35/0.5 instead of 1.0/0.4), while passive-defensive manifestations were not altered. In slowly learning animals (30%), hippocampal lesions were not accompanied by qualitative changes in the patterns of psychoemotional manifestations, while non-learning rats (60%) showed decreases in passive and increases in active manifestations (active/passive = 0.45/1.4 instead of 0.3/1.9). It is suggested that the hippocampus is involved in producing psychoemotional reactions, individual patterns of which depend on the morphofunctional characteristics of the system responsible for organizing the psychoemotional state.

Influence of hippocampectomy on habituation, exploratory behavior, and spatial memory in rats

Two frequently cited functions of the hippocampus are mediation of spatial memories and habituation. The present investigation employed head-shake response (HSR) as the habituated behavior in intact and bilaterally hippocampectomized rats. This HSR appears to be minimally influenced by spatial cues. These rats were further tested on two behavioral paradigms that make use of spatial cues, namely open field object exploration, and the Morris water maze. The results indicate that hippocampectomized rats revealed habituation of the HSR, but not to objects within the open field. In agreement with previous reports, hippocampectomized rats were severely impaired both in acquiring and recalling the location of the submerged platform in the Morris water maze task. In a separate experiment independent groups of rats were trained on one of these three paradigms, and tissues were collected from hippocampal, prefrontal, and piriform cortices for the measurement of matrix metalloproteinases (MMPs) as markers of neural plasticity. There were significant MMP-9 elevations in the prefrontal and piriform cortices of rats tested using the object exploration task, in the prefrontal and hippocampal cortices of rats that solved the Morris water maze task, but minimal MMP changes in any tissues taken from HSR habituated rats. These results question the hypothesis that habituation is solely mediated by the hippocampus in favor of a process that utilizes different brain structures and degrees of neural plasticity dependent upon task requirements.

Modulation of the Impairment of Hippocampectomized Rats on the Radial-Arm Maze Cue Task by Visual Characteristics and Subicular Damage.

Rats with N-methyl-D-aspartate lesions of the hippocampus that partially damaged the subiculum and controls were trained on 2 versions of the radial-arm maze cue task, with either proximal or distal visual stimuli. In Experiment 1, the relative positions of the stimuli varied across trials. Lesioned rats were impaired when trained on the distal version, as opposed to transiently slowed down when trained on the proximal version. In Experiment 2, the relative positions of the stimuli were fixed throughout training. Lesioned rats were impaired when trained on the distal or the proximal version. Further analyses showed that combined damage to the hippocampus and the subiculum was required to impair performance in the proximal, but not the distal, version.

Hippocampectomized rats can use a constellation of landmarks to recognize a place

The hippocampus, one of the most studied regions of the mammalian forebrain, plays some well-established roles in topographic navigation. For two decades, one widely accepted explanation for the observed impairment of hippocampectomized rats in spatial navigation has been an inability to form place representations. In this report, we present a direct experimental evidence that animals with hippocampal lesions can learn to recognize places using the constellation of distinct landmarks. The extrahippocampal implementation of all three basic constituents of topographic orientation — guidance, vector navigation, and place recognition — shows that the hippocampus, and its place cells, serve a much more specialized cognitive function than previously thought. We propose that this function includes multi-place and multi-vector topographic integration.

Neurotoxic Hippocampal Lesions Have No Effect on Odor Span and Little Effect on Odor Recognition Memory But Produce Significant Impairments on Spatial Span, Recognition, and Alternation

Recent work has shown that lesions of the hippocampus in monkeys cause deficits in the capacity to remember increasing numbers of objects, colors, and spatial locations (). However, others have observed that hippocampectomized monkeys can show intact memory for a list of objects or locations (). We wished to explore the effects of hippocampal damage on the capacity of memory in the rodent and, to do so, developed novel "span" tasks in which a variable number of odors or locations had to be remembered. In the odor span task (experiment 1), rats were trained on a nonmatching to sample task in which increasing numbers of odors had to be remembered. Half of the trained rats received ibotenic acid lesions of the hippocampus. Postoperatively, hippocampectomized animals did not differ from control animals even when required to remember up to 24 odors. However, when tested on delayed retention of a list of 12 odors, rats with hippocampal lesions were impaired at a long delay. Also, these rats were impaired on a subsequent test of delayed spatial alternation. In a spatial span task (experiment 2), naive rats were trained on a nonmatching to sample task in which a variable number of locations had to be remembered. After this, half of the animals received ibotenic acid lesions. Postoperatively, hippocampectomized animals performed above chance levels when required to remember a single cup location, but were unable to remember more. Subsequent testing on another spatial delayed alternation task suggested that hippocampectomized rats could recognize, but could not inhibit their approach to previously visited locations.

Effects of enriched postoperative housing conditions on spatial memory deficits in rats with selective lesions of either the hippocampus, subiculum or entorhinal cortex

Long-Evans male, adult rats received selective and bilateral lesions of either the hippocampus, subiculum or lateral entorhinal cortex, and were then housed for 30 days in either enriched or standard conditions. Rats were then tested in the eight-arm radial maze to assess spatial working memory and the strategies that were employed (i.e. pattern of arms visited). Lesions of the hippocampus induced both a working-memory impairment and a loss in the use of allocentric strategies to perform the task. Rats with lesions of the subiculum were also impaired but less than hippocampectomized rats and showed a similar pattern of arm visits as control rats. In contrast with other lesioned rats, rats with lateral entorhinal cortex lesions performed the task like control rats. Postoperative enriched housing conditions (EHC) globally enhanced performance of rats, but did not affect the strategies selected by the rats to solve the task. The beneficial effect of EHC was particularly obvious in rats with lesions of the subiculum. In enriched rats with such lesions, performance was not significantly different from that of control rats housed in standard conditions. The present results indicate that 1) the structures within the hippocampal formation are not similarly involved in spatial learning and memory processes and in the management of navigational demands of the radial maze, and 2) enriched conditions may enhance the spared spatial abilities of some lesioned rats thus promoting functional recovery.

Exposure to Predator Odor Reduces Locomotor Activity Levels in Adult Male Rats: Lack of Effect of Hippocampal Lesion

The hippocampus has been implicated in mediating responses to predators. Involvement of the hippocampus was tested in the present study in which a multivariate analysis of the locomotor activity of intact and hippocampectomized (destruction of dentate and CA1 cells) laboratory rats, Rattus norvegicus, was conducted following exposure to a predator odor. Levels of various activity variables were monitored in an automated activity monitoring system following a brief 3-min exposure to 2-propylthietane (weasel odor), caproic acid (goat odor), toluene (organic solvent), and a no-odor condition in hippocampal-lesioned (using colchicine) and sham-operated control male rats. Rats of both groups displayed reduced levels of total distance, movement time, vertical activity, and number of movements following exposure to weasel odor and toluene in comparison to the no-odor condition. Exposure to goal odor resulted only in reduced levels of vertical activity and number of movements. There were no differences in activity levels between hippocampal-lesioned and sham-operated rats during baseline activity recording or following exposure to any of the odors. However, hippocampal-lesioned rats spent less lime in the center of the activity boxes than sham-operated control rats across all conditions. This study demonstrates that laboratory rats show marked changes in locomotion in response to the odor of a predator and suggests that an intact hippocampus is not essential for mediating these responses.

Transplant-induced working memory deficits in hippocampectomized rats

This experiment determined the effects of transplantation of fetal hippocampus on the ability of male rats with hippocampal lesions to acquire versions of a radial arm maze that depended on either extramaze cues or intramaze cues for solution. Rats receiving transplants took significantly more trials than control rats to emit three consecutive errorless trials in the extramaze cue (spatial) variation of the maze. Rats with just hippocampal lesions never differed from any other group. No differences in this measure were found for the intramaze cue condition. Rats receiving transplants made more repeat entries into reinforced arms in both versions of the maze than control rats and more reentries into neverbaited arms in the spatial maze. Rats with hippocampal lesions failed to differ from any other group on this measure in the spatial maze, but were different from normal rats in the intramaze cue maze. These data suggest that in some tasks transplants of fetal tissue lead to greater behavioral impairment than lesions alone.

Effects of lesions in the medial pallium on instrumental learning in the toad ( Bufo arenarum)

Lesions of the medial pallium in toads significantly retarded extinction of a water-reinforced instrumental response in a runway training situation, relative to sham-operated and intact controls. The lesion had no effect on acquisition or in the amount of water uptake during acquisition. The results suggest that the medial pallium of toads plays a role in response inhibition. This possibility is discussed in relation to the results of analogous experiments with hippocampectomized rats.

The dorsal hippocampus modifies the negative feedback effect of glucocorticoids on the adrenocortical and median eminence CRF-41 responses to photic stimulation

In the present study we have evaluated the role of the dorsal hippocampus on the negative feedback effect of glucocorticoids (GC) following photic stimulation. In hippocampectomized rats the recovery of serum corticosterone (CS) to basal levels following photic stimulation, was significantly attenuated in relation to sham hippocampectomized rats. The inhibitory effect of either systemic dexamethasone administration or CS implanted in the paraventricular nucleus (PVN), on the adrenocortical responses to photic stimulation, was completely prevented in hippocampectomized rats in comparison to sham operated animals. In rats with sham operation, the depletion of median eminence CRF-41 induced by photic stimulation, was prevented by pretreatment with CS PVN implants or systemic dexamethasone. These effects were reversed in rats with dorsal hippocampectomy. The results suggest that the dorsal hippocampus modulates the negative feedback of GC on the adrenocortical response following photic stimulation at the PVN level and this effect is mediated by median eminence CRF-41.

Critical determinants of nonspatial working memory deficits in rats with conventional lesions of the hippocampus or fornix.

Rats with conventional lesions of the hippocampus or fornix were compared postoperatively with controls on nonspatial memory tasks. Neither lesion impaired delayed matching-to-sample (DMS) performance in a discrete-trial task involving "pseudo-trial-unique" complex stimuli. An impairment emerged if a single pair of complex stimuli was used throughout each day's session, and the greatest impairment was obtained with the use of a single pair of less complex stimuli throughout each day's test. Transfer to a continuous DMS task with no explicit intertrial interval produced a different pattern because both lesion and control levels of performance were depressed when two complex stimuli were used repeatedly. A final, separate discrimination learning experiment showed that hippocampectomized rats readily discriminated between the stimuli associated with the greatest lesion-induced DMS deficit. Hippocampal dysfunction thus produces clear deficits on non-spatial memory tasks under appropriate test conditions.

Ibotenate lesions of the hippocampus enhance latent inhibition in conditioned taste aversion and increase resistance to extinction in conditioned taste preference.

In 2 experiments, the effects of axon-sparing lesions of the hippocampus on performance in aversive and appetitive taste conditioning tasks were investigated. In Experiment 1, hippocampally lesioned rats showed no impairment of conditioned taste aversion learning relative to control subjects, but they did display an increased sensitivity to latent inhibition (LI). In Experiment 2, the same hippocampectomized rats acquired a conditioned taste preference but failed to show any evidence of extinction. The influence of the neurotoxic lesion on LI is in the opposite direction to the effect typically found following hippocampal damage induced by traditional methods. Accordingly, the data present challenges for most current theories of hippocampal function.

Choice behavior of hippocampectomized rats in the radial arm maze

Rats with hippocampal lesions (n = 16), sham-operated controls (n = 5), and unoperated controls (n = 8) were trained on place and cue tasks in an elevated radial arm maze. Hippocampallesioned rats had impaired working memory and impaired cognitive-map formation. The behavior of the hippocampals in choosing arms was different from that of the controls even immediately after training began. The hippocampals were not able to rapidly perceive the spatial requirements of the task and did not show the inherent stereotyped behavior employed by controls. Nonetheless, the hippocampals showed that they could learn problem-solving behavior as training progresses.

Rats with dorsal hippocampal lesions do react to new stimuli but not to spatial changes of known stimuli

The effect of visual distracting stimuli upon the straight alleyway performance of dorsal hippocampectomized Wistar rats was investigated. In comparison with control animals it was observed that dorsal hippocampectomized animals (1) ambulated more during the preexposure phase, (2) acquired at the same rate a running response for food (training phase), (3) reacted similarly to a new visual stimulus (black cards) presented in a sector of the alleyway, and (4) habituated to successive presentations of that stimulus in the same place. (5) However, dorsal hippocampectomized rats did not react, unlike the controls, to the presentation of the same stimulus in another place of the alleyway but (6) reacted to the visual pattern change of the stimulus (now black/white check cards) in the same place. These results indicate that under certain experimental conditions, hippocampus-lesioned animals are capable of interrupting a running response for food in order to explore a new conspicuously located stimulus, habituate to repeated presentations of that stimulus, and to react to a new pattern of visual stimulation. They suggest that hippocampectomized rats do not lose the capacity to react to a new stimulus; the disruption seems to be related to the spatial context of stimulus presentation, supporting a spatial mapping hypothesis of hippocampal function.

Glucocorticoid negative feedback and glucocorticoid receptors after hippocampectomy in rats.

In rats with dorsal hippocampectomy, glucocorticoid receptors in the hypothalamus and anterior pituitary, as well as the pituitary transcortin-like compound, are preserved, in spite of a 60% depletion of glucocorticoid receptors in the hippocampus. In the hippocampectomized group, basal levels of serum corticosterone (CORT) were increased, although there was a normal response to ether stress. Inhibition of the response to ether with dexamethasone (DEX) was dose-dependent: whereas 100 micrograms/kg completely suppressed serum CORT, 10 micrograms/kg were ineffective. However, we observed a reduced sensitivity to DEX inhibition with 25 micrograms/kg in hippocampectomized animals. These results indicate that the hippocampus is involved in negative feedback mechanisms, although different doses of DEX are needed for this demonstration. The inhibition of serum CORT due to 100 micrograms/kg DEX suggests that negative feedback at sites other than the hippocampus was still operative, in agreement with normal levels of glucocorticoid receptors in the anterior pituitary and hypothalamus of hippocampectomized rats.

Mineralocorticoid regulation of salt intake is preserved in hippocampectomized rats.

Considering the high concentration of binding sites for [3H]-aldosterone in the hippocampus, a relationship between these sites and the regulation of sodium appetite by aldosterone was investigated. After surgical hippocampectomy, rats showed an approximately 80% depletion of [3H]-aldosterone binding sites. In spite of this reduction, hippocampectomized rats developed a sodium appetite after adrenalectomy; this sodium appetite was suppressed by continuous administration of aldosterone, a response similar to the pattern found in normal rats. These results suggest that the hippocampus is not the main target of the effect of the hormone on salt intake.

Performance of hippocampectomized rats in a reference/working-memory task: Effects of preoperative versus postoperative training

Hippocampectomized and sham-operated male rats were pre- or postoperatively trained to perform a reference/working-memory task in a standard radial eight-arm maze. On each trial, three arms were baited. These “correct” arms formed one of two configurations, which changed between conditions. The remaining arms were never baited. The rats’ task was to enter each of the baited arms only once, and to refrain from entering any of the unbaited arms. Incorrect choices were punished with a brief period of confinement. Preoperatively trained groups were tested postoperatively for retention, and then trained on a new reference-memory task in which the baited arms formed the second configuration. Postoperatively trained groups were also trained on two such tasks in succession. Order of training on the two configurations was counterbalanced between groups. Postoperatively trained hippocampal groups were severely impaired in acquisition of the tasks. Preoperatively trained hippocampal groups were unimpaired, relative to sham-operated groups, in all measures of performance.

Successful overshadowing and blocking in hippocampectomized rats

Overshadowing (Experiment 1) and blocking (Experiment 2) were investigated using a conditioned suppression paradigm in rats. Neither hippocampectomy nor cortical control lesions affected the extent to which a salient stimulus overshadowed a less salient one. Nor did the lesions affect the extent to which a stimulus that was highly correlated with shock overshadow a stimulus that was less well correlated with shock. Finally, the lesions did not alter the extent to which a previously reinforced stimulus blocked conditioning to another stimulus when both were presented as a reinforced compound stimulus. It is thus possible for hippocampectomized rats to show apparently normal overshadowing and blocking, at least under some testing conditions.

Effects of serotonin synthesis inhibition on sleep in hippocampectomized rats

In adult rats an anterodorsal bilateral hippocampectomy produced an increase in motor activity without modification of the amount of the different sleep stages. In hippocampectomized rats p-chlorophenylalanine produced an insomnia which can be reversed by 5-HTP. These results show that the insomnia produced by brain serotonin depletion is not a result of the hyperactivity produced by the treatments which cause such depletion.