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Biomedical subjects

J N Rawlins

Publications and source records attributed to J N Rawlins.

At least 73 records · Page 4Linked to original sources
PubMed1992

Hippocampal aspiration lesions fail to impair performance of a delayed alternation GO/NO-GO task.

Rats with hippocampal aspiration lesions (HIPP), cortical control lesions (CORT) or sham operations (SHAM) were trained on a delayed alternation GO/NO-GO task, in which responding was reinforced on odd-numbered GO trials but was not reinforced on even-numbered NO-GO trials. The number of responses required to obtain reinforcement, and the length of the inter-trial intervals (ITIs), were varied in different stages of the experiment. These systematic parametric manipulations were conducted in order to compare the roles of intra- and inter-trial information and the temporal spans which could be bridged in performing the task across the three different lesion groups. In addition, at a later stage of testing interference was introduced during the ITI to investigate its effect on task performance. The differences observed between the HIPP, CORT and SHAM groups were generally non-specific for trial type, with HIPP animals responding more overall on both NO-GO and, to a lesser extent, GO trials following each of the ITIs used. The results were consistent with the behavioural inhibition theory of hippocampal function, but not with the temporal discontiguity or working memory models. These surprising findings contrast sharply with those observed following an electrolytic lesion of the hippocampus, which has been reported to produce a delay-dependent impairment of performance on the GO/NO-GO task in rats using a very similar procedure. It is speculated that differences in performance following aspiration and electrolytic lesions may be at least partially attributable to rats adopting different response strategies induced by ITI differences in the two tasks. However, the results also raise an important question concerning the assumed equivalence of aspiration and electrolytic lesions of the hippocampus. The possibility that an interaction between procedural and lesion differences may contribute to the discrepant findings is also considered. The findings illustrate the sensitivity of the hippocampal mnemonic effect on what has become an established testing procedure in the hippocampal literature.

Animals↗
PubMed1992

Mammillary body lesions and restricted subicular output lesions produce long-lasting DRL performance impairments in rats.

Rats given either electrolytic lesions of the mammillary bodies (MB), transection of the descending columns of the fornix (DCF), transection of fibres projecting from subiculum to ventral striatum (SC) or sham operations (SO) were tested in three DRL experiments. DRL-18 efficiency was impaired significantly in MB rats, and non-significantly in DCF and SC rats. Analysis of timing behaviour revealed modifications in all three lesion groups, with a unique pattern in the SC group. DRL-36 efficiency was significantly impaired in all three lesion groups; the SC group again showed a unique timing pattern. Finally we assessed retention of DRL-36 in SO rats given mammillary body lesions. There was a lesion-induced impairment, smaller than that seen with postoperative training. We propose that the subicular output plays an important part in normal DRL performance; that the subicular outputs to the mammillary bodies and ventral striatum play independent roles in DRL; and that the effects of mammillary body lesions resemble those of hippocampal lesions because of the important functional relationship between subiculum and the mammillary bodies.

Animals↗
PubMed1992

A neuroleptic-like effect of ceronapril on latent inhibition.

Three experiments that used a latent inhibition procedure to investigate the effects of ceronapril on attentional processes in the rat are reported. Latent inhibition is a behavioural paradigm in which prior exposure to a stimulus with no significant consequences retards subsequent conditioning to that stimulus when it is paired with reinforcement. Latent inhibition reflects a process of learning to ignore, or tune out, irrelevant stimuli, and has been suggested as an animal model of the attentional processes disrupted in the acute phase of schizophrenia. In animals, latent inhibition is disrupted by the administration of low doses of amphetamine and enhanced by the administration of neuroleptics. Ceronapril is an angiotensin converting enzyme inhibitor that has been shown to retard the breakdown of central cholecystokinin. It has been proposed that elevation of cholecystokinin levels in the brain may possess neuroleptic-like properties. We assessed this possibility by determining the effects of ceronapril on latent inhibition using a conditioned emotional response procedure, consisting of three stages: pre-exposure, in which the to-be-conditioned stimulus, a tone, was repeatedly presented without reinforcement; conditioning, in which the pre-exposed stimulus was paired with shock; and test, where latent inhibition was indexed by animals' suppression of licking during tone presentation. In Experiment 1, 20 tone pre-exposures were given, and conditioning consisted of five tone-shock pairings; we assessed the effects of 0.005 mg/kg, 0.05 mg/kg and 0.5 mg/kg ceronapril, compared with vehicle injections. In Experiment 2, five tone pre-exposures were given, and conditioning consisted of two tone-shock pairings: we assessed the effects of 0.05 mg/kg ceronapril, compared with vehicle injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1992

Aspiration lesions of rat ventral hippocampus disinhibit responding in conditioned suppression or extinction, but spare latent inhibition and the partial reinforcement extinction effect.

Latent inhibition refers to a decrement in learning about a stimulus as a result of its prior non-reinforced presentation. There is evidence that lesions of nucleus accumbens and conventional hippocampal lesions both disrupt the development of latent inhibition. The partial reinforcement extinction effect reflects the observation that resistance to extinction is normally greater in animals that have been rewarded on a 50% random proportion of acquisition trials than in those rewarded on every trial. Conventional hippocampal lesions, excitotoxic lesions of hippocampus plus subiculum, or conventional lesions of nucleus accumbens abolish this effect. The present experiments examined the possibility that a projection originating in the ventral [temporal in the nomenclature proposed by Blackstad: (1956) J. comp. Neurol. 105, 417-537] subiculum and terminating in nucleus accumbens underlies the normal development of latent inhibition and the partial reinforcement extinction effect, by evaluating the performance on these two behaviours of rats with aspiration lesions in the ventral hippocampal region. There was equally clear evidence of latent inhibition and of a partial reinforcement extinction effect in controls and in rats with ventral hippocampal damage. However, superimposed on this, the hippocampal lesion induced a loss of behavioural inhibition in both paradigms. Subsequent anatomical analyses indicated that cell bodies in nearby retrohippocampal cortex had maintained intact projections to nucleus accumbens. We suggest that these extra-hippocampal projections may underlie the ability to learn to ignore irrelevant stimuli.

Analysis of Variance↗
PubMed1991

Electrolytic lesions of the nucleus accumbens in rats which abolish the PREE enhance the locomotor response to amphetamine.

The partial reinforcement extinction effect (PREE) refers to the increased resistance to extinction observed in animals trained on a partial reinforcement (PR) schedule compared with those trained on a schedule of continuous reinforcement (CR). It has been suggested that the PREE is dependent upon the integrity of the septo-hippocampal system, but recent evidence has indicated that the role originally proposed for the lateral septal nucleus may in fact be subserved by the nucleus accumbens. Experiment I therefore tested the effects of electrolytic lesions of the nucleus accumbens on the PREE. These lesions abolished the PREE, the abolition resulting from a decreased rate of extinction in the lesion CR rats coupled with an increased rate of extinction in the PR rats. These results clearly implicate the nucleus accumbens in the development of the PREE, and suggest that theoretical models of the PREE based simply upon consideration of septohippocampal interactions need radical revision. The lesion also enhanced running speeds in acquisition in both the CR and the PR groups. Experiment II therefore assessed spontaneous locomotor activity and the locomotor response to amphetamine challenge at two doses. The lesion produced no increase in spontaneous locomotion; an enhanced increase in response to 1 mg/kg amphetamine; and no changes in the stereotyped behaviours induced by 10 mg/kg amphetamine.

Amphetamine↗
PubMed1991

The competitive NMDA antagonist AP5, but not the non-competitive antagonist MK801, induces a delay-related impairment in spatial working memory in rats.

Rats were trained to alternate responses on a discrete trial working memory task on a T-maze. In Experiment 1, the rats were then matched for choice accuracy and allocated to three treatment groups. These were: implantation of osmotic minipumps for intraventricular infusion of either (a) 15 mM D-2-amino-5-phosphonopentanoic acid (AP5) or (b) artificial cerebrospinal fluid (VEH); and an unoperated control group (UNOP). In Phase 1 we assessed alternation performance with a minimal delay between responses: the UNOP and VEH rats continued to choose accurately; the AP5 rats showed an impairment of choice accuracy, but recovered over days. In Phase 2 a 20-s delay between responses was enforced, and choice accuracy was assessed following injections either of saline or of Milacemide HCl (10 mg/kg). There was now a severe and enduring impairment of choice accuracy in the AP5 group, but Milacemide injections did not affect performance in any of the treatment groups. In Experiment 2 rats were trained in a similar way, and then given intraperitoneal injections of MK801 or of physiological saline in a within-subjects design and tested for T-maze performance with a minimal or a 20-s delay between responses. In the first Phase, MK801 was given 10-min before behavioural testing commenced; in the second Phase, it was given 28-40 min before behavioural testing commenced. The outcome depended critically on the time between drug injection and testing. There was a significant drug-induced impairment of choice accuracy in both Phases; but in Phase 1 there was no impairment in testing with a minimal retention interval and an impairment with a 20-s retention both retention intervals. We conclude that AP5, but not MK801, interferes with temporary memory storage in a delay-dependent manner.

2-Amino-5-phosphonovalerate↗
PubMed1990

Effects of GABAergic drugs, fornicotomy, hippocampectomy and septal lesions on the extinction of a discrete-trial fixed ratio 5 lever-press response.

The effects of certain GABA-modulating drugs, fornicotomy, hippocampectomy and various septal lesions were analysed in a discrete-trial fixed ratio 5 (FR5) bar-press paradigm. Chlordiazepoxide, fornicotomy, hippocampectomy, electrolytic lateral septal lesions and ibotenic acid medial septal lesions facilitate extinction of the FR5 response. Some of these treatments (chlordiazepoxide, hippocampectomy, electrolytic lateral septal lesions) have previously been found to increase resistance to extinction of alley-running after continuously reinforced (CRF) acquisition training. The treatments which facilitated extinction in the discrete-trial FR5 paradigm have been found to reduce or abolish the partial reinforcement extinction effect in the alley. These results indicate that the discrete-trial FR5 paradigm is not analogous to a runway CRF schedule, but may be analogous to a runway partial reinforcement schedule.

Animals↗
PubMed1990

The effects of ibotenic acid lesions of the nucleus basalis and cholinergic-rich neural transplants on win-stay/lose-shift and win-shift/lose-stay performance in the rat.

Rats were trained to criterion performance in 2-lever operant conditional memory tasks that required them to follow either a Win-stay/Lose-shift, or else a Win-shift/Lose-stay response rule. Substantial impairments in performance of both pretrained conditional tasks were seen following ibotenic acid lesions of the nucleus basalis, but not of the globus pallidus. The deficit in both tasks was apparent at all inter-response retention intervals, indicating that nucleus basalis lesions produced a general impairment in the performance of the complex conditional operant tasks, and not a specific deficit in short-term memory. The nucleus basalis lesion rats were then divided into groups matched for equivalent performance. One group was given cell suspension grafts into neocortex of E15 cholinergic-rich forebrain tissue; a second group was given similar grafts of E17 hippocampal tissue; and a third group was given sham transplants. Testing beginning 3 months post-transplant showed that there was no evidence of recovery of performance on these tasks in the cholinergic-rich transplanted groups compared to the controls. However, the rats with cholinergic-rich transplants subsequently showed a significant improvement in retention of a step-through passive avoidance task. The results indicate that either cholinergic deafferentation of the neocortex is not critical for the observed deficits in the operant conditional tasks, or recovery of function following cholinergic-rich transplants is task-specific, in that more complex cognitive tasks may require different levels of graft-host neural integration.

Animals↗
PubMed1990

Section of the descending columns of the fornix produces delay- and interference-dependent working memory deficits.

Rats were allocated to one of three surgical treatment groups, and given either sham operations (SHAM), transection of the descending columns of the fornix (DCF), or transection of fibres at the base of the lateral septal nuclei (SC). They were trained on a rewarded alternation task, run as a spatial working memory task on an elevated T-maze, with a minimal intratrial interval. There were no differences between the SHAM and the SC rats. The DCF rats showed an initial impairment in acquisition, but their performance gradually improved to control levels. The imposition of a 20-s intratrial interval impaired choice accuracy in all groups, but the extent of the impairment was significantly greater in the DCF group. Addition of an extra, and conflicting, 'information run', to provide a source of proactive interference, also impaired performance in all groups, but the impairment was again greatest in the DCF group, suggesting that this lesion increases intrusion errors. Subsequent testing in the acquisition of 2-way active avoidance revealed that the DCF lesion facilitated learning with respect to the other two groups. The results indicate that there are clear functional differences between the different outputs from the subiculum, and that the descending subicular output plays a significant role in normal memory.

Animals↗
PubMed1990

An investigation into the early stages of the inflammatory response following ibotenic acid-induced neuronal degeneration.

Injection of the excitatory neurotoxin ibotenic acid into the septum produces rapid destruction of neuronal cell bodies and accompanying gliosis. We have previously shown that following ibotenate-induced cell death this may also result in damage to healthy axons en passage (Coffey et al., Neurosci. Lett. 84, 178-184, 1988). We suggested that the axonal damage resulted from non-specific damage by recruited inflammatory cells. In this study we have further examined the phenotype of the cells involved in the inflammatory response in the rat. Immunocytochemical identification of cells in the region of the lesion site identifies them as being of haematopoitic origin and most of them have the phenotype of macrophages. The dramatic increase in their number following an ibotenate lesion is sensitive to irradiation of the body providing evidence that the majority are blood derived. The inflammatory response is accompanied by a loss of myelin and a breakdown of the blood-brain barrier in the region of the lesion site. We have shown that these two effects are consequences of the inflammatory response since reduction in the inflammatory response by prior irradiation will abrogate these two effects.

Animals↗
PubMed1989

Ibotenate-induced total septal lesions reduce resistance to extinction but spare the partial reinforcement extinction effect in the rat.

Rats were given sham operations, vehicle injections, or injections of the axon-sparing excitotoxin ibotenic acid into the septum. In Experiment 1, behavioural testing commenced 16 days after the operation; in Experiment 2 behavioural testing commenced following testing on another task, 31 days after the operation. The rats were trained to run in an alley for food reward given on every trial (Continuous Reinforcement, CR) or on a random fifty percent of trials (Partial Reinforcement, PR) and then the running response was extinguished. All the experimental groups showed the normal partial reinforcement extinction effect (PREE) in that PR-trained animals were significantly more resistant to extinction than CR-trained animals. However the rats with ibotenic acid lesions also showed a significant decrease in resistance to extinction regardless of training condition. The same pattern of results was seen at each of the two post-operative testing times. The results were thus readily replicable, and entirely unlike previous reports of the behavioural effects on this task of conventional septal lesions of equivalent size. In Experiment 3, neurochemical analysis of the hippocampus in rats with ibotenic acid-induced lesions demonstrated that choline acetyl-transferase levels were reduced to the same extent as in rats with comparable conventional lesions.

Animals↗
PubMed1989

The role of subicular outputs in the development of the partial reinforcement extinction effect.

Rats were trained to run in an alley for food reward given on every trial (Continuous Reinforcement, CR) or on a random fifty percent of trials (Partial Reinforcement, PR) and the running response was then extinguished. Sham Operated controls showed the normal partial reinforcement extinction effect (PREE) in that PR-trained animals were significantly more resistant to extinction than CR-trained animals. The PREE was abolished by a knife cut placed at the base of the lateral septum to interrupt ventral subicular fibres destined for the ventral striatum. This outcome stemmed purely from a decrease in resistance to extinction in the lesion PR group. A large lesion that also sectioned the dorsal subicular pathway in the descending columns of the fornix left the PREE intact, though there were some signs of a reduction in its size primarily due to increased resistance to extinction in the lesion CR group. We conclude that previous reports demonstrating reduction or abolition of the PREE following conventional total septal or lateral septal lesions, may have achieved their results through damage to subicular fibres en passage through the septum.

Animals↗
PubMed1989

Effects of amygdaloid and amygdaloid-hippocampal lesions on object recognition and spatial working memory in rats.

Neurotoxic lesions of the amygdala did not affect the postoperative acquisition of a nonspatial test of object recognition (delayed nonmatching to sample) even when retention delays were increased from 0 s to 20 or 60 s, or when test stimuli were deliberately repeated within a session. Although these amygdaloid lesions did not alter forced-choice spatial alternation, they slightly increased neophobic responses to novel foods and environments. In contrast, combined amygdalohippocampal (A + H) lesions impaired performance on the object recognition task when the retention intervals were increased beyond 0 s and when test stimuli were repeated within a session. The A + H rats were also severely impaired on the spatial alternation task, and they showed reduced neophobia. Comparisons with a previous study show that damage to the amygdala or hippocampus does not affect object recognition, whereas A + H damage produces clear deficits.

Amygdala↗
PubMed1989

Retinal transplant-mediated learning in a conditioned suppression task in rats.

Retinae were transplanted from embryonic rats to a location over the midbrain of unilaterally anucleated newborn rats. At maturity, the rats were trained to "lever-press" for a food reward. By using a Pavlovian conditioned suppression paradigm, it was found that light delivered to the transplant could be recognized by the host rat as a conditioned stimulus, resulting in a reduced rate of lever pressing.

Animals↗
PubMed1988

The effects of fornix section on win-stay/lose-shift and win-shift/lose-stay performance in the rat.

Two groups of rats were trained in 2-lever operant tasks that required them to follow either a Win-shift/Lose-stay rule, or else a Win-stay/Lose-shift rule. The rats in each testing condition attained a similar level of performance. Once the tasks had been learnt, half of the rats in each testing condition were given fornix lesions. These lesions produced a clear performance impairment at all inter-response retention intervals tested in those rats trained on the Win-shift/Lose-stay task, but impaired performance in rats trained on the Win-stay/Lose-shift condition only when the inter-response interval reached 10 s. The implications of these results for the working memory theory and for the temporal discontiguity theory are discussed.

Animals↗
PubMed1988

Ibotenic acid induced demyelination in the central nervous system: a consequence of a local inflammatory response.

We examined the effects of injections of ibotenic acid into the medial septum (MS), dorsal lateral geniculate nucleus (dLGN), caudate-putamen (CP) or fornix-fimbria (FF) on fibres close to the injection site. Injections into the MS and dLGN resulted in demyelination. The area of demyelination correlated with the area of maximal gliosis. The major cell type in the area of gliosis were cells of haemopoietic origin, as revealed by using monoclonal antibodies (Mabs). Demyelination was not observed in the CP or FF. Axonal transport in fibres en passage through the dLGN lesion was also disrupted following injections of horseradish peroxidase (HRP) into the eye contralateral to the lesion. These results show that when ibotenic acid induces cell death it can secondarily damage myelin sheaths and disrupt axonal transport in areas containing diffuse fibre systems. We suggest that this is due to a non-specific effect of the inflammatory response.

Animals↗