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J N Rawlins

Publications and source records attributed to J N Rawlins.

At least 91 records · Page 5Linked to original sources

Intra-ventricular infusion of the NMDA antagonist AP5 impairs performance on a non-spatial operant DRL task in the rat.

Rats were trained to lever press on a differential reinforcement of low rates (DRL-18 s) schedule. They were then allocated to four treatment groups. These were: hippocampal aspiration lesions [HIPP]; implantation of osmotic minipumps for intraventricular infusion of either (a) the NMDA receptor antagonist 30 mM D, L-2-amino-5-phosphonopentanoic acid [AP5] or (b) vehicle [VEH]; and an unoperated control group [UNOP]. In subsequent DRL testing, the HIPP group showed a profound and enduring loss of efficiency, resulting from an increased tendency to respond too early; the AP5 group showed a qualitatively similar, but less severe, impairment followed by full recovery once the minipumps had expired; the VEH and UNOP groups both maintained their pre-operative levels of efficiency. We conclude that AP5 infusion disrupts temporary memory storage in the hippocampus, and that the hippocampus is concerned with the retention of memories outside the purely spatial domain.

2-Amino-5-phosphonovalerate↗

The hippocampus and conditioning to contextual cues.

Two experiments are reported in which behavioral control by contextual cues was assessed in groups of rats with dorsal hippocampal (HC), neocortical (NC), or operated control (OC) lesions. Following Odling-Smee's (1975) procedure, a Pavlovian conditioning paradigm was followed in which conditioned stimuli (CSs: tone, light) predicted an unconditioned stimulus (US:footshock) always, never, or half the time. Conditioning trials took place in a small black box. Subsequently, conditioning to background contextual cues was assessed by measuring the amount of time rats spent in the black box in preference to an adjacent white one with neither CS nor US presented. In OC groups and, to a lesser extent, NC groups, conditioning to background cues was inversely related to the probability that CS predicted US. In contrast to graded contextual conditioning in control groups, the HC groups consistently showed abnormally strong conditioning to context that was at or near asymptotic level. The results, which were related to current theories of the relation between contextual stimuli and CSs, suggest that the hippocampus may play an important role in stimulus selection during learning.

Animals↗

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.

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The effects of hippocampal lesions upon spatial and non-spatial tests of working memory.

A series of experiments examined the proposal that the primary effect of hippocampal damage in rats is to disrupt working memory. Although extensive hippocampal lesions produced a severe impairment in forced-choice alternation--a test of spatial working memory--the same lesions did not impair the acquisition of a non-spatial test of working memory--delayed non-matching-to-sample. This test of object recognition required the rats to select that arm in a Y-maze which contained unfamiliar stimuli. Rats with hippocampal lesions were able to learn and perform this task at normal rates, even with retention delays of as long as 60 s. Two additional experiments helped confirm that the animals had indeed learnt a non-spatial test of working memory. The final experiment examined whether hippocampal lesions resulted in an increased sensitivity to proactive interference. It was found that repetition of test stimuli within a session, which increased interference, did attenuate recognition performance but there was no evidence that the animals with hippocampal lesions were differentially affected.

Animals↗

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↗

Resistance to extinction after schedules of partial delay or partial reinforcement in rats with hippocampal lesions.

Two experimental procedures were employed to establish the reason why hippocampal lesions apparently block the development of tolerance for aversive events in partial reinforcement experiments, but do not do so in partial punishment experiments. Rats were trained to run in a straight alley following hippocampal lesions (HC), cortical control lesions (CC) or sham operations (SO), and resistance to extinction was assessed following differing acquisition conditions. In Experiment 1 a 4-8 min inter-trial interval (ITI) was used. Either every acquisition trial was rewarded immediately (Continuous Reinforcement, CR), or only a randomly selected half of the trials were immediately rewarded, the reward being delayed for thirty seconds on the other trials (Partial Delay, PD). This delay procedure produced increased resistance to extinction in rats in all lesion groups. In Experiment 2 the ITI was reduced to a few seconds, and rats were trained either on a CR schedule, or on a schedule in which only half the trials were rewarded (Partial Reinforcement, PR). This form of partial reinforcement procedure also produced increased resistance to extinction in rats in all lesion groups. It thus appears that hippocampal lesions only prevent the development of resistance to aversive events when the interval between aversive and subsequent appetitive events exceeds some minimum value.

Animals↗

Fornix-fimbria section and 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 50% of trials (partial reinforcement, PR) and were 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 significantly reduced by lesions of the fornix-fimbria. The reduction was largely a consequence of a reduction in resistance to extinction in PR-trained rats with fimbria-fornix lesions. These results are discussed in the light of other experiments that have studied disconnections in the septo-hippocampal system.

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The effects of delaying reward on choice preference in rats with hippocampal or selective septal lesions.

Two experiments are reported in which rats were trained to choose one of two goal arms in a Y-maze, for water reward. In one arm, the rats always received water (the continuously reinforced-CRF-arm). In the other arm the rats only sometimes received water (the partially reinforced-PRF-arm). During the critical test phase in both experiments, we delayed the reward in the CRF arm only by 10 s. Experiment 1 tested intact rats given saline injections, or injections of chlordiazepoxide hydrochloride (Librium, 5 mg/kg), and rats with hippocampal or cortical control lesions. When reward was immediate in both arms all rats preferred the CRF arm. Once reward was delayed, the rats with hippocampal lesions switched their preference to the PRF arm, while the rats in the other treatment groups did not. Experiment 2 tested rats with medial septal lesions, lateral septal lesions or control operations in the same way. The rats with medial septal lesions, and to a lesser extent those with lateral septal lesions, switched their preference to the PRF arm when compared to the sham-operated controls. We conclude that damage to the hippocampus or its afferent pathway from the septum increases rats' sensitivity to temporal discontiguities between the outcome of a response and its emission.

Animals↗

Habituation of the shortening reflex in the medicinal leech.

The shortening reflex was elicited in food-sated Hirudo medicinalis by light flashes delivered at 20-s intervals over a 40-trial session. The reflex was enhanced if animals were stored at 5-7 degrees C rather than 20 degrees C. Short-term, that is, within-sessions, habituation was readily observed. Dishabituation could be produced by a single electric shock at Trial 30. However, the shock also enhanced responding when delivered before Trial 1 (sensitization). No long-term, that is, between-sessions, habituation occurred over 6 consecutive days of testing; on the contrary, responding gradually increased.

Animals↗

Voltammetrically monitored brain ascorbate as an index of excitatory amino acid release in the unrestrained rat.

To discover the significance of changes in the extracellular concentration of brain ascorbate, we used linear sweep voltammetry to monitor the ascorbate signal. Recordings were made with carbon paste electrodes implanted in the striatum and hippocampus of anaesthetised and unanaesthetised rats under a variety of conditions. Intraperitoneal administration of excitatory amino acid transmitters, but not tyrosine or glycine, increased extracellular striatal ascorbate; similarly, microinfusion of L-glutamate beside striatal electrodes enhanced the ascorbate signal. Electrical stimulation of the perforant path increased the extracellular concentration of dentate ascorbate in the unanaesthetised, but not in the anaesthetised, rat. These results support our hypothesis that changes in the extracellular concentration of brain ascorbate monitored by voltammetry reflect the release of excitatory amino acids.

Amino Acids↗

Dorsal bundle lesions do not affect latent inhibition of conditioned suppression.

Three experiments are reported which examine the effects of lesions of the dorsal ascending noradrenergic bundle (DB) on latent inhibition using a conditioned suppression procedure in rats. In none of the experiments did the DB lesion have any effect, despite changes in the extent of latent inhibition and in the control procedures used to assess it. The results are discussed in relation to the attentional theory of DB function.

Animals↗

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.

Animals↗

Tetanus toxin as a tool for studying epilepsy.

The use of tetanus toxin, injected into the hippocampus of the rat, to produce an "animal model" of chronic limbic epilepsy is described. This model has yielded information complementary to that derived from other animal models and has several important advantages: while it involves spontaneous seizures, it occurs without gross damage to the brain ; it is eventually reversible in terms of fits and the overall reappearance of the EEG. It can therefore be used to look both at the effects of ongoing epilepsy and also at the long-term changes in brain function induced by previous epilepsy. Evidence is presented that the toxin probably remains localised at the site of injection. The information which has so far been obtained with this model on the relation between epilepsy and abnormal behaviour is summarised. In particular, it appears that the epilepsy produces long-term deficits in the animals' ability to learn and remember of a sort which suggest that an enduring malfunction has been induced in the hippocampus. The significance of the findings for clinical research and for future investigation of the nature of epilepsy are described. It is emphasised that the neurotoxins may be usefully exploited not only for investigating the molecular basis of neuronal mechanisms but also for inducing long-lasting plastic changes in integrated brain function.

Animals↗

Hippocampal lesions do not alter the partial punishment effect.

Rats were trained to run in an alley for food reward. In a 'partial punishment' condition the animals also received occasional footshock in the goalbox; controls received only food reward during training. In a test phase all animals were given both food and footshock in the goalbox on every trial. Previously partially punished animals demonstrated greater persistence in running to the goal during this test phase. This 'partial punishment effect' was unchanged by hippocampectomy whether the experiment was conducted with an inter-trial interval of a few minutes or one of 24 h. The presence of the partial punishment effect in hippocampectomised rats is in sharp contrast with the abolition of the partial reinforcement extinction effect (which is very similar to the partial punishment effect, but based upon nonreward rather than punishment) previously reported after hippocampectomy.

Animals↗

The hippocampus, time and working memory.

Rats were trained on a discrete trial working memory leverpress alternation task, following hippocampal lesions (HC), cortical control lesions (CC) or sham operations (SO). Each trial consisted of a forced information response, for which a randomly selected lever was presented followed by a free choice stage, when both levers were presented. The rats were rewarded for pressing the lever which had not been presented at the information stage. When the information response was not rewarded, all rats learnt the task equally well at IRIs of up to 12.75 sec. When the information response was rewarded, the HC rats showed impaired choice accuracy. The extent of this impairment depended on the IRI, being greatest at long IRIs, and least at short ones. Varying the number of leverpresses required to complete the information response affected choice accuracy equivalently in all groups: all rats chose significantly less accurately when only one leverpress was required than when ten leverpresses were required. There was no interaction between the lesion treatments and the information response requirements. It was concluded that both the length of the IRI and the occurrence of events during the IRI determine the extent of the hippocampal lesion-induced performance deficit in working memory tasks. It is proposed that hippocampal damage disrupts an intermediate-term, high-capacity memory buffer, but leaves both a residual short-term memory system and the long-term retention of associations unaffected. This proposal leads to the prediction that reference memory tasks should also be affected by hippocampal lesions when a delay is introduced between making a response and being rewarded for doing so.

Animals↗

The hippocampus, collateral behavior, and timing.

Rats with hippocampal lesions (HC), cortical control lesions, or sham operations were trained to lever press on a differential reinforcement of low rates (DRL) schedule requiring 12 sec between responses. In four experiments, factors affecting performance efficiency in this paradigm were manipulated. Providing extra opportunities for collateral mediating behavior (Experiment 1) aided all groups nondifferentially. Adding a limited hold (Experiment 2) or administering chlordiazepoxide HCl (Experiment 3) reduced DRL efficiency in all groups nondifferentially. However, adding an auditory stimulus marking the halfway point in the DRL requirement (Experiment 4) differentially aided the HC group. The implications of these findings for different theories of hippocampal function are discussed.

Animals↗