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Biomedical subjects

L E Jarrard

Publications and source records attributed to L E Jarrard.

At least 37 records · Page 2Linked to original sources
PubMed1993

Hippocampal lesions do not impair negative patterning: a challenge to configural association theory.

According to configural association (CAS) theory (Sutherland & Rudy, 1989), an intact hippocampus is required for rats to solve learning problems that are based on "configural" processes. This theory identifies the negative patterning discrimination as a critical example of this type of problem. Rudy and Sutherland (1989) reported disruption of negative patterning following hippocampal formation damage produced by intracranial infusion of a mixture of kainic acid + colchicine (KA + COL). We assessed acquisition of negative patterning in rats with hippocampal damage produced by KA + COL compared with rats with more selective ibotenate lesions of hippocampus. Neither group showed impaired negative patterning relative to controls. A transfer test provided evidence that all groups used configural processes to solve the problem. Thus contrary to CAS theory, the hippocampus is not an important substrate for the operation of configural processes.

Acoustic Stimulation↗
PubMed1993

Selective excitotoxic pathology in the rat hippocampus.

The pattern of cell loss and neuronal degeneration resulting from multiple microinjections of N-methyl-D-aspartate (NMDA), ibotenate (IBO), quisqualate (QUIS), and kainate (KA) into hippocampus was studied, together with the protection provided by the NMDA antagonist 3-(+/-)-2-carboxypiperazin-4-yl-propyl-1-phosphonate (CPP). Histological evaluation was carried out after 7 days of survival. NMDA and IBO resulted in an extensive loss of all cells in the hippocampus including dentate gyrus, hilar cells, and CA3-CA1 pyramidal cells, but there was an absence of damage to areas and structures outside hippocampus. After QUIS and KA injections the hippocampal damage was limited to hilar cells in the dentate gyrus, CA3 pyramidal cells, and partial loss of CA1 cells; there was extensive extrahippocampal damage including entorhinal cortex, amygdala, layers III, V, and VI of ventral neocortex, olfactory areas, and various thalamic nuclei. CPP provided almost complete protection from the effects of intrahippocampal injections of NMDA and IBO, but did not affect the hippocampal cell loss found after QUIS and KA (with the exception of minor protection of some CA1 cells). CPP protected most extrahippocampal sites from the damage resulting from QUIS and KA, indicating that such excitotoxic cell death is indirect and involves NMDA receptor activation by an endogenous agent. The use of multiple microinjections as opposed to single injections allows a clearer interpretation of selective excitotoxic vulnerability.

Animals↗
PubMed1992

Effects of medial and lateral septal lesions on acquisition of a place and cue radial maze task.

Rats with lesions limited to either the medial septal (MS) or dorsolateral septal (LS) nuclei were trained on a place and cue version of the radial maze using a procedure that permits determination of both reference memory (RM) and working memory (WM). Following training the presence or absence of hippocampal theta for MS and LS groups was determined. The results showed that both MS- and LS-lesioned rats were impaired in acquisition. Specifically, the pattern of results indicated a general impairment in working memory that was found on both the place and cue tasks together with impaired acquisition of the place (but not the cue) task. While both septal lesion groups evidenced a similar impairment, rats in the MS group made more errors than LS rats on several components of the tasks. Electroencephalographic recordings revealed that hippocampal theta was not affected in the LS group but was abolished in rats with MS lesions. Thus, it appears that the functional role of the septo-hippocampal system cannot be fully described by a single mechanism or process but rather several processes seem to be affected when the septal area is damaged.

Animals↗
PubMed1992

Strategy selection in a task with spatial and nonspatial components: effects of fimbria-fornix lesions in rats.

The main purpose of the present research was to investigate the ability of rats to learn a 12-arm radial maze task that requires the concurrent utilization of both spatial and intramaze cue information. The task involves in a single trial both place and cue learning as well as reference memory (RM) and working memory (WM). Since the animal can choose place and cue arms in any order, the strategies employed to learn the task can be studied as well as the kinds of memory errors that are made. The results of Experiment 1 showed that the number of errors made on the place and cue components of the task did not differ, and that more RM than WM errors were made early during learning. As the task was learned, the animals tended to choose the place arms before choosing the intramaze cue arms, thus suggesting that a spatial strategy was employed first followed by a cue strategy. In Experiment 2 lesions of the fimbria-fornix resulted in temporary impairments in both RM and WM that were especially apparent on the spatial component of the task. The lesioned rats also switched from choosing mostly place arms early during the trial to choosing more cue arms. While fimbria-fornix lesioned rats recovered from the memory impairments with training, the change in response strategy persisted throughout postoperative testing. The procedure of combining both spatial and non-spatial components concurrently in the same task should prove of value in studying response strategies in animals.

Animals↗
PubMed1992

Potency of food deprivation intensity cues as discriminative stimuli.

Rats were trained to use stimuli arising from 0 and 24 hr without food as discriminative signals for shock. In Experiment 1, one group was shocked under 0-hr food deprivation and not shocked under 24-hr food deprivation. Another group received the reverse contingency. The groups received only 3 training trials under each deprivation level. Learning was revealed in a test phase when greater extinction of freezing was observed under the nonshocked than under the shocked deprivation level for both groups. A similar pattern of results was obtained in Experiment 2 when auditory cues were also relevant throughout training. Furthermore, prior training with food deprivation cues seemed to reduce learning about auditory cues subsequently trained in compound with deprivation stimuli. The results indicate that food deprivation intensity cues can be potent discriminative stimuli. The idea that deprivation cues function as conditioned modulatory stimuli cues is also discussed.

Animals↗
PubMed1991

On the hippocampus and learned conditional responding: effects of aspiration versus ibotenate lesions.

To study the possible involvement of the hippocampus in learned conditional responding, rats with aspiration lesions of the hippocampus and others that had the hippocampus removed with ibotenic acid were trained on concurrent Pavlovian conditional and nonconditional discriminations. In agreement with the results reported by Ross et al. (1984), animals that had the hippocampus removed with aspiration were unable to learn the conditional discrimination, but learned the simple nonconditional discrimination without difficulty. In contrast, rats that had the hippocampus removed with ibotenic acid did not differ from controls in learning either discrimination. Furthermore, transfer test results were consistent with the hypothesis that ibotenate-lesioned rats performed conditional operations to solve the conditional discrimination problem. Histological analysis indicated that the ibotenate lesions resulted in the removal of the hippocampus and dentate gyrus with minimal involvement of other structures. In aspiration hippocampal animals there was less overall damage to the hippocampus, but there was also extensive damage to the axons passing in alveus and fimbria, together with bilateral loss of cells in the subicular complex, the cingulate gyrus, and the cortex. Since rats with ibotenate lesions had more complete removal of the hippocampus, yet learned both discriminations, the impaired conditional responding found in aspiration hippocampals must be due to extrahippocampal damage.

Animals↗
PubMed1991

Selective fimbria and thalamic lesions differentially impair forms of working memory in rats.

Several series of experiments were designed to compare the effects of selective lesions of the fimbria or of thalamic nuclei on three different tasks involving working memory in rats: object recognition, place recognition, and the radial arm maze test. The main effects of fimbria lesions were as follows: they produced deficits in the radial maze; object recognition was spared or even facilitated, whereas place recognition was impaired. Electrolytic lesions of either centromedian-parafascicularis (CM-Pf) or dorsomedialis (DM) nuclei produced highly significant deficits in the radial maze test but spared object and place recognition. Ibotenate lesions of the CM-Pf had no effect on any test, which means that the critical structure in the effects of the electrolytic lesions of the CM-Pf was the fasciculus retroflexus (FR). These data may contribute two main points to animal models of hippocampal and thalamic amnesia: (1) different forms of working memory in rats might have different neural bases and (2) the FR may be involved in learning and memory processes.

Animals↗
PubMed1991

Complementary roles for the amygdala and hippocampus in aversive conditioning to explicit and contextual cues.

Experiment 1 investigated the effects of catecholaminergic deafferentation or cell body lesions of the amygdala on fear conditioning to explicit and contextual cues. Bilateral infusions of quinolinic acid mainly damaged neurons within the basolateral region of the amygdala. 6-Hydroxydopamine infusions at the same coordinates resulted in an 86% depletion of noradrenaline and a 63% depletion of dopamine from the amygdala, but had no effect on the concentration of 5-hydroxytryptamine. After recovery from surgery, lesioned rats and controls were exposed to pairings of an auditory (clicker) conditioned stimulus and (foot shock) unconditioned stimulus in a distinctive environment. During testing, rats with both 6-hydroxydopamine and cell body lesions showed severely impaired conditioning to explicit cues, compared with controls, indicated by their reduced suppression of drinking when the conditioned stimulus was introduced into a separate, lick-operant chamber. Neither lesion affected fear conditioning to contextual cues, measured as preference for a "safe" environment over the one in which they were shocked. In Experiment 2, rats received bilateral, ibotenic acid-induced lesions of the hippocampal formation. Lesioned rats and controls were again tested for aversive conditioning to explicit and contextual cues. Rats with cell body lesions of the hippocampus showed normal suppression of drinking in the presence of the conditioned stimulus, but were severely impaired in choosing the safe environment based on contextual cues alone. These results suggest a double dissociation of the effects of amygdala and hippocampal damage on fear conditioning to explicit and contextual cues.

Amygdala↗
PubMed1989

Scopolamine impairs both working and reference memory in rats: a replication and extension.

Rats were trained to run in a spatial, radial maze for sucrose reward using a procedure that permitted determination of two memory functions [working memory (WM) and reference memory (RM)]. Injections of saline, 0.1, 0.4, and 0.8 mg/kg of scopolamine hydrobromide were administered using a Latin-square design; a single dose (0.4 mg/kg) of scopolamine methylbromide served as a control for peripheral drug effects. The smallest dose of scopolamine (0.1 mg/kg) had no measurable effect on performance, but as the dose was increased to 0.4 and 0.8 mg/kg there were increases in both WM and RM errors, in errors of omission, and increases in running time. These results support the view that the effects of scopolamine on performance in the radial maze is not specific for working memory, but rather the effects are more general in nature.

Animals↗
PubMed1989

On the use of ibotenic acid to lesion selectively different components of the hippocampal formation.

Procedures are described for lesioning two components of the hippocampal formation (hippocampus, subiculum) using multiple injections of small amounts of ibotenic acid (IBO). The resulting loss of cells is more selective and limited than can be obtained with conventional techniques. Thus, problems associated with damage to adjacent areas, fibers-of-passage, and damage to the vasculature are minimized. The results of behavioral experiments indicate that the effects of IBO lesions of the hippocampus are more subtle than those found with conventional lesion techniques. The general approach of using multiple injections of small amounts of neurotoxins can be used to selectively lesion other components of the hippocampal formation.

Animals↗
PubMed1989

Effects of anterior or dorsomedial thalamic ibotenic lesions on learning and memory in rats.

Sprague-Dawley rats were used to study the effects of ibotenic acid lesions of the anterior (A.Th.) and the dorsomedial (MD) thalamic nuclei on learning and memory. Memory was assessed by employing a temporal alternation task in a straight alley with varying intertrial intervals. In addition, spatial orientation and response flexibility were evaluated on a radial maze and on a spatial reversal task (SSDR). The results indicated that MD rats required more trials to learn the temporal alternation task and exhibited impaired performance compared to A.Th. and control groups at the shortest delay (15 s). In contrast, compared to the control group, A.Th. subjects which required less trials to master the task and exhibited normal performance at the 15-s delay were impaired when the intertrial interval was increased to 45 s. Whatever the lesion, no impairments were found in the SSDR or the radial maze while only MD lesions were found to result in a night hyperactivity associated with greater food and water consumptions. These findings indicate that A.Th. and MD are differentially involved in learning and memory processes. It is suggested that the MD is mostly involved in registering new information while the A.Th. plays a role in the maintenance of information over time.

Animals↗
PubMed1988

The effects of intra-subicular ibotenate on resistance to extinction after continuous or partial reinforcement.

Intracerebral injections of ibotenate were used to produce, in rats, extensive cell loss in the subiculum. These rats and sham-operated controls were trained to run in a straight alley for food reward delivered on a continuous (CR) or partial (PR) reinforcement schedule. In controls PR training gave rise to the well-known partial reinforcement extinction effect (PREE), i.e., greater resistance to extinction than that observed in CR-trained animals. Previous experiments have shown that large aspiration lesions of the hippocampal formation eliminate the PREE; and that ibotenate-induced lesions of the subicular region plus either the hippocampus or the entorhinal cortex disrupt it. In contrast to these previous results, the PREE was unaltered in the present experiment by damage largely restricted to the subiculum. This lesion caused only relatively small changes in running speeds during acquisition. Thus the critical region(s) of damage within the hippocampal formation for disruption of the PREE remains uncertain.

Animals↗
PubMed1988

Acquisition of a complex place task in rats with selective ibotenate lesions of hippocampal formation: combined lesions of subiculum and entorhinal cortex versus hippocampus.

The effects of isolating the hippocampus from its neocortical inputs and outputs by damaging the deep layers of entorhinal cortex and subiculum were compared with direct removal of the hippocampus using acquisition of a complex radial maze task. A series of eight problems (four out of eight arms being correct) were learned under either massed (45 s) or distributed (10 min) practice conditions, thus varying contextual information. Performance of rats with subiculum/entorhinal cortex lesions was similar to that of controls in all aspects of the radial maze task; whereas animals with hippocampal lesions were impaired on nearly all dependent measures. Although the effects of varying the intertrial interval were generally small, distributed practice did serve to facilitate the performance of hippocampal rats in terms of working memory. These findings are discussed as they related to recent theorizing in the area.

Animals↗
PubMed1986

The effects of intrahippocampal ibotenate on resistance to extinction after continuous or partial reinforcement.

Intracerebral injections of ibotenate were used to produce, in rats, extensive cell loss in the hippocampus and dentate gyrus (complete hippocampal, CH), in the CH plus subiculum (SUB + CH), or in the subiculum plus entorhinal cortex (SUB + EC). These rats and sham-operated controls were trained to run in a straight alley for food reward delivered on a continuous (CR) or partial (PR) reinforcement schedule. In controls PR training gave rise to the well-known partial reinforcement extinction effect (PREE), i.e., greater resistance to extinction than that observed in CR-trained animals. Previous work had shown that large aspiration lesions of the hippocampal formation eliminate the PREE by increasing resistance to extinction in CR-trained animals and decreasing resistance to extinction in PR-trained animals. In the present experiments the PREE survived CH lesions, which increased resistance to extinction in both CR and PR training conditions; these effects were observed in the start and run (but not goal) sections of the alley. In contrast, subicular cell loss (in both SUB + CH and SUB + EC groups) abolished the PREE (but in the goal section only) by increasing resistance to extinction in the CR condition and decreasing resistance to extinction in the PR condition. In addition, some of the effects of PR training on start and run speeds during acquisition were altered by the CH and SUB + CH lesions. These results confirm previous data showing that the hippocampal formation plays a role in mediating the behavioural effects of PR training, but require modification of the model previously proposed to account for these data.

Animals↗
PubMed1986

Selective cytotoxic lesions of the hippocampal formation and DRL performance in rats.

Rats were given injections of ibotenic acid that made lesions of neurons throughout the hippocampus (CHC), or restricted to area CA3 (CA3), or to the subiculum (SUB), and were trained to lever press on a differential reinforcement of low rates (DRL) schedule. Their performance efficiency was compared with that of sham-operated (SO) rats in three experiments. Acquisition of DRL 12 s was only slightly impaired by any of the lesions. Increasing the DRL requirement to 18 s did not affect asymptotic efficiency of responding in the SO, CA3, or SUB group but markedly reduced efficiency in the CHC group. Administration of scopolamine reduced efficiency to the same extent in rats in all surgical treatment groups. It is concluded that hippocampal lesions made with ibotenic acid resemble conventional hippocampal lesions in their behavioral effects on DRL performance; that the behavioral effects of scopolamine administration do not appear to depend on disruption of activity of cholinoceptive cells in the hippocampal formation; and that DRL schedules, although highly sensitive to septohippocampal system disruption, discriminate more between the extent than the location of lesions in the system.

Animals↗