Hippocampal Animals Research Articles

Context-dependent extinction learning emerging from raw sensory inputs: a reinforcement learning approach

The context-dependence of extinction learning has been well studied and requires the hippocampus. However, the underlying neural mechanisms are still poorly understood. Using memory-driven reinforcement learning and deep neural networks, we developed a model that learns to navigate autonomously in biologically realistic virtual reality environments based on raw camera inputs alone. Neither is context represented explicitly in our model, nor is context change signaled. We find that memory-intact agents learn distinct context representations, and develop ABA renewal, whereas memory-impaired agents do not. These findings reproduce the behavior of control and hippocampal animals, respectively. We therefore propose that the role of the hippocampus in the context-dependence of extinction learning might stem from its function in episodic-like memory and not in context-representation per se. We conclude that context-dependence can emerge from raw visual inputs.

Hippocampal lesions, contextual retrieval, and autoshaping in pigeons

Both pigeons and rats with damage to the hippocampus are slow to acquire an autoshaped response and emit fewer overall responses than control animals. Experiment 1 explored the possibility that the autoshaping deficit was due to an impairment in contextual retrieval. Pigeons were trained for 14 days on an autoshaping task in which a red stimulus was followed by reinforcement in context A, and a green stimulus was followed by reinforcement in context B. On day 15, the subjects were given a context test in which the red and green stimuli were presented simultaneously in context A and then later in context B. Both control and hippocampal animals showed context specificity, that is, they responded more to the red stimulus in context A and to the green stimulus in context B. In Experiment 2 we video-recorded the control and hippocampal animals performing the autoshaping task. Hippocampal animals tended to miss-peck the key more often than control animals. In addition, the number of missed pecks increased across days for hippocampal animals but not for control animals, suggesting that while the control animals increased their pecking accuracy, the hippocampal animals actually decreased their pecking accuracy. Our findings suggest that impairments in moving through space may underlie the hippocampal autoshaping deficit.

Effects of lesions to the hippocampus or the fornix on allocentric conditional associative learning in rats.

Rats with lesions of the fornix, the hippocampus, or normal control animals were trained on a visual-spatial conditional associative learning task in which they had to learn to go to a particular location based on the presence of a specific visual cue; the rats approached the cues from different directions. Animals with damage of the fornix were able to learn the task at a rate comparable to that of the control animals. The performance of the hippocampal rats was significantly impaired as compared with the control group. Both the fornix and the hippocampal animals were significantly impaired on a spatial working memory task, the eight-arm radial maze. These findings suggest that, under certain conditions, a functional dissociation exists between the effects of damage to the fornix or the hippocampus and that the fornix may be only selectively involved in spatial learning and memory.

The hippocampus and flexible spatial knowledge in rats.

Lesions to the hippocampal system in rats result in a profound impairment of place or locale spatial learning although other learning strategies remain unaltered. The main objective of the present study was to investigate whether the spatial knowledge preserved in the hippocampal animals can be expressed flexibly under conditions different from those of the acquisition period. Rats with neurotoxic lesions to the dorsal hippocampus and sham-operated subjects were trained to reach the goal arm in a four-arm plus-shaped maze using a constant starting arm. During the training a transparent plexiglas barrier divided the maze in two equal halves in such a way that the animals could only travel from the starting arm to the goal arm, not having access to the remaining 50% of the maze. After seven days of training, a transfer test was used in which the starting arms were the two arms from which the animals had not started during the training phase. Results indicated that the lesioned rats made significantly more errors than the control subjects. But the most interesting results revealed that the kind of error made by the lesioned animals was congruent with the turn that they had to make during the acquisition phase in order to access the goal arm (reinforced). These results suggest that when the hippocampus is damaged a preserved highly inflexible egocentric strategy is employed to solve the spatial problem.

Long‐term spatial memory in rats with hippocampal lesions

In animal models of human amnesia, using lesion methods, it has been difficult to establish the role played by the hippocampus in the formation of long-term spatial knowledge. For example, lesions sustained after acquisition have generally produced a flat retrograde amnesia for spatial information. These results have not made it possible to dissociate the participation of the hippocampus in retrieval/performance processes from its participation in consolidation/retention. The present study was designed to investigate if electrolytic hippocampal lesions made before training lead to a deficit in the long-term retention of spatial knowledge when the rats show equal performance levels during the acquisition. Results show that lesioned rats learn a place response just as well as the control rats when, during the training, an intramaze cue orients the animal in its navigation towards the goal arm. One day after reaching criterion, lesioned and control rats remember the task perfectly during a transfer test in which the intramaze signal used previously is not present. However, 24 days later, the hippocampal animals manifest a profound deficit in the retention of the spatial information. When the spatial task learned during the acquisition phase requires only the use of a guidance strategy, control and lesioned animals show the same level of performance during the training phase and the same degree of retention during the retraining phase 24 days after criterion. Taken together, these results suggest that the hippocampus plays a crucial role in long-term retention of allocentric spatial information.

A comparison of the effects of hippocampal or prefrontal cortical lesions on three versions of delayed non-matching-to-sample based on positional or spatial cues

We trained rats to perform one of three versions of delayed non-matching-to-sample (DNMS): DNMS between two retractable levers in an enclosed operant chamber; varying-choice DNMS between two arms selected at random on every trial in an uncovered eight-arm radial arm maze; or recurring-choice DNMS between the same two arms on every trial in a covered radial maze ( N=33/task). Rats with medial prefrontal cortical lesions showed delay-independent impairments on the retractable lever and recurring-choice tasks, but performed varying-choice DNMS normally. Rats with hippocampal lesions exhibited delay-independent impairments of the retractable lever task and delay-dependent impairments of both radial maze tasks. When rats trained initially to perform recurring choice DNMS were switched to varying choice DNMS, the impairments of both the prefrontal and hippocampal groups were reduced, although hippocampal animals remained significantly impaired. When rats trained initially to perform varying choice DNMS were switched to recurring choice DNMS, the impairment of the hippocampal group was exacerbated while the prefrontal group remained unimpaired. Thus training the prefrontal group to perform the varying choice task first seemed to protect from impairment when these rats were subsequently trained to perform recurring choice DNMS. This protection provides evidence against the possibility that factors related to proactive interference or to temporal discrimination can account for the effects of prefrontal lesions on delayed conditional discriminations involving two response alternatives in fixed locations.

Neurotoxic lesions of the dorsal hippocampus disrupt auditory-cued trace heart rate (fear) conditioning in rabbits.

The first experiment in this study used the classical heart rate (HR) conditioning paradigm to determine if rabbits could associate an auditory conditioned stimulus (CS) and a fear-producing shock-unconditioned stimulus (US) separated by an empty 10-s trace interval. Trace conditioned rabbits (n = 7) acquired significant bradycardiac conditioned HR responses on CS-alone test trials during a single 35-trial conditioning session. Control animals (n = 7) which received unpaired CSs and USs did not show HR conditioning. During a retention session of CS-alone trials 24 h after the conditioning session, some trace-conditioned animals showed conditioned HR responses immediately following CS onset (n = 3), while others showed responses appropriately timed to the US onset (n = 4) used in trace conditioning 24 h earlier. Thus, rabbits remember the duration of the long 10-s trace interval 24 h after a single day of training. The second part of this study sought to determine if cells in the dorsal hippocampus play a role in trace HR conditioning. Rabbits were given bilateral ibotenic acid lesions in the neocortex (n = 7) or dorsal hippocampus (n = 8). During trace conditioning and retention, neocortical animals showed conditioned HR responses to the CS, whereas the hippocampal group showed no significant HR conditioning. One week after trace conditioning, the same animals received a delay HR conditioning session where no trace interval separated the CS and US. During delay conditioning, hippocampal animals showed significant conditioned HR responses to the CS that were similar to the neocortical group. Thus, the dorsal hippocampus plays a critical role in rabbit HR conditioning when the CS and US are separated by a 10-s trace interval. This paradigm may be ideal for in vivo electrophysiological recording studies because rabbits are easily immobilized during the testing procedure, and learning occurs during a single day of training.

Effects of confinement, previous experience and hippocampal damage on the DRL schedule

Rats with dorsal hippocampal (HIPP) and cortical (CX) lesions and control animals were tested for acquisition of a differential reinforcement of low rate of responding (DRL-20 s) task in a 6-compartment apparatus that permitted running, drinking and other activities. HIPP and CX animals and one group of control rats (NOR) were trained in an ‘open’ condition which allowed a variety of activities, while another control group (CON) were trained while confined to the food and lever area of the apparatus. In the second stage of the experiment conditions were reversed. DRL performance was significantly better in the ‘open’ condition for all groups: more pellets were gained with fewer lever presses. Groups HIPP performed worse than groups NOR and CX in both conditions. When NOR and CX rats were confined to the food area they developed a jumping behaviour, (attempts to leave the food area) which increased throughout the testing period, coupled with a progressive deterioration of performance. Rats initially trained in the ‘confined’ condition did not develop jumping. HIPP animals were significantly more active; they produced more lever presses, entered the different compartments more frequently and showed higher activity in the running wheel. The schedule-induced interim behaviour in the open condition was wheel-running in all groups. In the HIPP group the number of jumps was significantly less than in the NOR and CX groups i.e. they were less affected by confinement. These findings suggest that previous experience in the ‘open’ condition has a strong anterograde, seemingly irreversible, consequence on subsequent behaviour in the ‘confinement’ condition for normal and cortical control rats and this anterograde effect is less pronounced in animals with hippocampal damage.

Retention and acquisition of classical trace conditioned responses by rabbits with hippocampal lesions.

The effects of dorsal hippocampal lesions on retention of classical trace conditioned responses were examined using the rabbit nictitating membrane preparation. Animals were trained to criteria and then lesioned either in the cortex or in the hippocampus and the cortex. Hippocampal damage had no effect on the retention of responses but produced significantly longer onset latencies. A control group of hippocampal animals acquired conditioned responses (CRs) at least as quickly as the prelesion subjects, and they also exhibited longer response onset latency. A second experiment evaluated the performance of hippocampal lesioned animals in classical trace conditioning with either a low-intensity periorbital shock or corneal air puff as the unconditioned stimulus (UCS). Hippocampal animals successfully acquired CRs under both conditions but exhibited an alteration of response onset which was dependent on the form of the UCS. Hippocampal animals displayed shorter response onset in the air-puff condition and longer response onset in the shock condition. Cortical animals timed responses consistently regardless of the UCS. These findings strongly suggest that the hippocampus modulates temporal characteristics of learned behavior.

Biochemical indices of reactivity and habituation in rats with hippocampal lesions

The response of rats with hippocampal lesions to acute and repeated footshock stress was assessed by measurement of pituitary cyclic AMP, plasma corticosterone and plasma prolactin. Levels of pituitary cyclic AMP and plasma prolactin and corticosterone were similar in never-shocked sham controls, and never-shocked hippocampal and neocortical lesion groups. Acute first time shock markedly elevated all measured stress indices with no statistically significant differences observed among surgical groups. In rats subjected to repeated stress (one 15 min footshock session per day for 10 days) and sacrificed 24 hours after the last shock session, levels of pituitary cyclic AMP and plasma hormones were similar to levels in never-shocked shams with the exception of the hippocampal animals. The rats with hippocampal lesions had higher levels of pituitary cyclic AMP, plasma corticosterone and plasma prolactin compared to never-shocked animals. We suggest that these data reflect a hyperreactive response of the hippocampal animals to a situation previously associated with shock. Finally, rats in all surgical groups subjected to repeated stress and sacrificed immediately after the last shock session showed a diminished cyclic AMP response to the stressor as compared to first footshock session response, demonstrating a habituation to the stressor as measured by this index. No differences in habituation were observed among hippocampal, neocortical and sham groups. Plasma hormone responses did not habituate in any group. These data support the behavioral observations of hyperreactivity in hippocampal animals and indicate that hippocampal animals are able to habituate to repeated stressful stimuli.

Disruption of latent inhibition by placement of an electrode in the dorsal hippocampus

Rats were implanted unilaterally with electrodes placed in either the dorsal hippocampus or the mesencephalic reticular formation. Subgroups were given either zero or six preexposure trials to a tone that was subsequently paired with a footshock. An additional group of dorsal hippocampal animals was given 12 preexposure trials. Test performance indicated that all groups given preexposure trials, with the exception of the dorsal hippocampal group given six such trials, showed latent inhibition. A second experiment suggested that the disruption of latent inhibition in the dorsal hippocampal animals given six preexposure trials was not due to seizure activity. The implications of these results are discussed.

Passive avoidance learning in hippocampectomized rats under different shock and intertrial interval conditions

Two experiments were run comparing the performance of normal, cortically damaged and hippocampally damaged rats on a passive avoidance task [37]. The results of Experiment 1 indicated that hippocampally damaged rats learn to passively avoid after no more than three consecutive punishment trials. In Experiment 2, the passive avoidance performance of groups of normal, cortically damaged, or hippocampally damaged rats was studied using a factorial combination of two intertrial intervals (60 sec and 60 min) and two shock intensities (1.8 mA and 1.8 mA). Results indicated that the greatest and most persistent deficits in the performance of hippocampally ablated animals occurred in the low shock, short intertrial interval condition. No differences between the performance of hippocampally damaged animals and control animals were found in the high shock, long intertrial interval condition. Performance of the hippocampectomized animals in the remaining groups was poorer than controls, but intermediate between the performance of the hippocampal animals in the aforementioned groups. Results were interpreted as supporting an information processing model of hippocampal function.

Effets de l'environnement sur la restauration fonctionnelle après lésions hippocampiques chez des rats adultes

The effects of post-operative environment on recovery of learning capacity after hippocampal lesions were studied in male rats of the August strain; the rats were 120 days of age when the lesions were inflicted. Half the subjects received bilateral lesions of the dorsal hippocampus by the electrolytic method; the other half had sham operations. Five days after the operations half of each group was placed in an enriched environment and the other half in an impoverished environment. After 60 days in these differential environments, the rats were pretrained and tested in the 12 standard problems of the Hebb-Williams maze. Performances in this test were significatively affected by the lesion and the environment. Hippocampal rats made significantly more errors than controls ( p<0,01) and enriched rats made significantly fewer errors than the impoverished rats ( p<0,001). The effects of environment are more pronounced in hippocampal animals than in controls: the interaction between these factors is significant ( p<0,001).

Effects of context manipulation on memory and reversal learning in rats with hippocampal lesions.

In Experiment 1, groups of hippocampal and control rats learned a simultaneous discrimination habit and were subsequently tested for its retention under variable contextual conditions. All groups recalled the discrimination response to an equally high level when testing conditions were constant throughout, but the hippocampal group showed impaired memory when contextual stimuli at recall testing did not conform to those of original learning. Experiment 2 indicated that the hippocampal impairment was not simply the result of introducing novel stimuli. In Experimental 3, animals were administered a reversal learning task with contextual stimuli varied between the two tests. The typically observed impairment of hippocampal animals on this task was reduced by contrasting contextual conditions. The data are seen to support a contex-tetrieval interpretation of hippocampal function.

P-Chlorophenylalanine-produced effects on behavior in intact and brain-damaged rats

Introduction: Our aim was to determine if a reduction of serotonin (5-HT) synthesis in the brain would provide any protection from the behavioral alterations induced by hippocampal brain-damage. The development of open-field activity (5 minute sessions) over two weeks and the acquisition of a passive avoidance task were chosen for study. Methods: There were 3 groups of lesioned rats - those hippocampal aspiration lesions, those with only damage to the neocortex overlying the hippocampus, and a sham-operated group. Half of each group was treated 300 mg/kg p-chlorphenylalanine (PCPA) for 3 successive days to deplete levels of 5-HT and the other half were given the saline vehicle alone. [Hippocampal damage is associated with increased activity in the open field and impaired learning of the step-through passive avoidance response.] Results: 1/ Animals with hippocampal damage became hyperactive in the second week after operation. 2/ PCPA treatment had no effect on locomotion, (nor on the frequently observed thigmotaxic nature of the behavior) 3/ Rearing was initially depressed after the operation, and PCPA treatment facilitated its recovery - but PCPA decreased rearing in intact animals during the second week of testing. 4/ Reduced levels of grooming were seen in hippocampal animals, while PCPA reduced grooming in those with neocortical damage 5/ The animals with hippocampal damage were impaired in witholding response in the passive avoidance task - those treated with PCPA performed even worse in not witholding the shock-reinforced step-through response. This contrasted with the intact animals, where PCPA treatment reduced the amount of footshock the animals were exposed to in the task Conclusions: .The results are consistent with a role for mesolimbic 5-HT innervation of the dorsal hippocampus having an influence on novelty-elicited responses (e.g. grooming in home vs. novel cage and investigative rearing behavior) and in modulation of the sensitivity of response to electric footshock (hypersensitive in PCPA-intact animals, hyposensitive in PCPA-hippocampal animals).

Effects of hippocampal lesion on cardiovascular, adrenocortical and behavioral response patterns in mice

It was found that animals with a hippocampal lesion developed high blood pressure, low heart rates, and high plasma corticosterone during social interaction in a territorial situation. However, hippocampal animals kept in a nonterritorial situation with minimal social interaction did not show significant cardiovascular or plasma corticosterone changes as compared to unoperated controls or cortically lesioned controls. The socially interacting hippocampal animals failed to develop a social hierarchy and did not respond aggressively to an intruder placed in the colony. The data suggests that the hippocampus is involved in the maintenance of social behavior which in turn may modulate autonomic nervous system activity.

Influence of hippocampectomy on gastric ulcer in rats

Hippocampectomized male rats were prepared, and the incidence as well as severity of gastric ulceration upon restraint were compared with those of normal control animals and controls with localized damage to the cortex over the hippocampus. In another experiment, observations on gastric ulceration were made without restraint in hippocampectomized animals, normal controls, controls with cortical damage, vagotomized animals and animals that received hippocampectomy as well as vagotomy. Both in restrained and unrestrained states, the incidence of animals with ulcer as well as the number and the total area of ulcers per stomach were significantly larger in the hippocampal animals than they were in the other animal groups. Vagotomy abolished the effect of hippocampectomy upon gastric ulceration in the unrestrained state. We infer that the hippocampus helps to protect the stomach from ulceration partly by controlling vagal activity.

Situational control over electrically induced ingestive behavior: A comparison of hippocampal and hypothalamic feeding

Either hippocampal or hypothalamic stimulation was used to induce feeding in rats during five 1/2-h conditioning sessions. Subsequently, the animals were tested for feeding in the same situation, but without brain stimulation. During the no-stimulation condition, the hippocampal animals ate more than the hypothalamic animals and unstimulated control animals. The hypothalamic animals did not differ from controls on the no-stimulation days. These findings indicate that ingestive behavior induced by brain stimulation can come under situational control but that this phenomenon is dependent upon electrode placement.

Hippocampal lesions during rearing and transfer of perceptual learning in rats

Bilateral lesions of the hippocampus in humans result in severe deficits of recent memory which consist of an inability to recall events a few minutes after they have occurred. On the other hand, such patients demonstrate normal abilities to recall events that transpired before the operation. Studies employing animals as subjects have produced contrary evidence concerning a memory-consolidation view of hippocampal functioning because hippocampal animals are not deficient in learning a variety of tasks. In the present research, the recent memory hypothesis was reexamined employing the early experience paradigm of Gibson and Walk (1956). This methodological variation provided a testing situation more analogous to the human testing situation in that animals were required to utilize salient cues from their environment and to transfer this information to a subsequent discrimination task. It was found that animals receiving bilateral hippocampectomy before exposure to the to-be-discriminated stimuli fared no better in a subsequent discrimination test than animals not exposed to the stimuli. In addition, animals undergoing hippocampal ablation after exposure to the forms demonstrated significantly better performance in the test situation than nonexposed animals. The findings of the present research provide some support for the recent memory hypothesis of hippocampal functioning.

The effects of hippocampal-pyriform ablations on the acquisition and transfer of cues in successive discrimination by cats

The acquisition and transfer performance of six cats with hippocampal-pyriform ablations was compared with that of seven normal animals. All animals were trained on a successive, go/no-go, auditory-brightness discrimination (Task 1). Ss were tested for transfer to the auditory and/or brightness cues of Task 1 by training them on similar discriminations using only the brightness cue (Task 2) or the auditory cue (Task 3). The hippocampectomized Ss were inferior to the normals on acquisition of Task 1 (p <.022), but they were not significantly different from the normals on the two transfer tasks (2: p < 0.394; 3: p < 0.662). These results support the hypothesis that previous experience with the relevant cues of a successive discrimination is a crucial factor in reducing acquisition deficits on that discrimination by hippocampal animals.