Serial Reversal Research Articles

A comparison of the effects of frontal cortical and thalamic lesions on measures of spatial learning and memory in the rat

Two experiments were conducted to compare the effects of radiofrequency lesions of thalamus and frontal cortex on three measures of spatial learning and memory: delayed non-matching to sample (DNMTS), radial arm maze with imposed delays, and serial reversal learning. Thalamic lesions were aimed at the lateral internal medullary lamina (L-IML) and cortical lesions at the projection areas of the mediodorsal nucleus along the medial wall (MW) and dorsal to the rhinal sulcus (RS) in frontal cortex. In Experiment 1 rats were trained on DNMTS prior to surgery. After recovery, rats with MW lesions showed persistent deficits on DNMTS that were significantly greater than for RS lesions. The deficits observed in MW lesioned animals were comparable to the effects of L-IML lesions on this task that have been described in previous studies. In Experiment 2 animals were trained to perform the radial arm maze task prior to treatment. After recovery, animals with L-IML lesions were impaired on the radial arm maze and on subsequent acquisition of the serial reversal task. Rats with RS and MW lesions showed transient impairments on the radial arm maze task, but otherwise performed as well as controls on both these tasks.

Styrene Impairs Serial Spatial Reversal Learning in Rats

To evaluate the effects of styrene exposure on learning, adult male Long-Evans rats learned repeated reversals of a spatial discrimination task. Styrene monomer (50% vol/vol in corn oil) was administered by gavage to groups of eight rats at 500 mg/kg/day, 5 days/week, for 8 weeks in Experiments (Exps) I and II (total dose = 20.0 g/kg) or for 1,3,5, or 8 weeks in Exp III (total dose = 2.5, 7.5, 12.5, or 20.0 g/kg). Control rats received corn oil vehicle for 8 weeks. Reversal training began 8 (Exp I), 10 (Exp II), or 32 (Exp III) weeks after termination of dosing. In Exp I, an instrumental (IN) schedule was used, under which rats received food after each presentation of a “positive” response lever (S+ ) only if they had made at least one response during that presentation of S+. In Exps II and III, an automaintenance (AU) schedule was used, under which rats received food after every presentation of S+, regardless of responding. In all experiments, a second manipulandum (S°) was presented randomly in time with respect to S + and food delivery. A discrimination ratio (DR) was calculated as the proportion of total responses on S+ in each block of 10 trials. A reversal involved switching the reward values of S+ and S°. Serial reversal learning was quantified in terms of trials to criterion. Reversal learning improved similarly in control and treated rats trained under the IN schedule, whereas treated rats trained under the AU schedule failed to improve as much as controls. Reversal learning of some styrene-treated AU rats in Exp III continued to be impaired for > 1 year after treatment. Increased responding on S° featured prominently in the behavioral effect of styrene. An IN schedule requiring suppression of S° responses for food in Exp III revealed a clear deficit in rats exposed to styrene. Not all treated rats were affected by styrene; nevertheless, changes in the affected individuals were as large as those previously observed after trimethyltin-induced lesions of the CNS. The incidence of impairment was not related to the total dose of styrene given, suggesting the action of other, undetermined factors affecting individual sensitivity to styrene.

Alternating prism exposure causes dual adaptation and generalization to a novel displacement.

In two experiments, we examined the hypothesis that repeatedly adapting and readapting to two mutually conflicting sensory environments fosters the development of a separate adaptation to each situation (dual adaptation) as well as an increased ability to adapt to a novel displacement (adaptive generalization). In the preliminary study, subjects alternated between adapting their visuomotor coordination to 30-diopter prismatic displacement and readapting to normal vision. Dual adaptation was observed by the end of 10 alternation cycles. However, an unconfounded test of adaptive generalization was prevented by an unexpected prism-adaptive shift in preexposure baselines for the dual-adapted subjects. In the primary experiment, the subjects adapted and readapted to opposite 15-diopter displacements for a total of 12 cycles. Both dual adaptation and adaptive generalization to a 30-diopter displacement were obtained. These findings may be understood in terms of serial reversal learning and "learning to learn."

Stimulus-bound perseveration after frontal ablations in marmosets

Marmosets with bilateral ablations of either the lateral or ventral surface of the frontal lobes were found to perseverate on object but not spatial serial reversal. They also perseverated on reversal of a visuospatial task where different stimuli required different spatial responses. No differences were found between the two lesion groups. Since the control animals showed mild perseveration on spatial but not object serial reversal it is argued that frontal ablations do not lead to perseveration of a natural tendency but rather that object and visuospatial perseveration are forms of stimulus-bound behaviour which do not occur when the animal is performing a spatial task in which stimulus position is irrelevant. Perseveration was reduced by pretreatment with a dopamine-blocking drug (haloperidol). It is suggested that information from temporal lobe mechanisms, involved in long-term memory, and from frontal lobe mechanisms, which exert shorter acting influences on behaviour, compete within the basal ganglia to determine stimulus choice. The ascending dopaminergic pathway may modulate the balance between these competing factors.

Chapter 30 Responses of monkey basal forebrain neurons during visual discrimination task

Publisher Summary The chapter discusses the results of a study of organization in the monkey basal forebrain of visual information concerning real objects. It was found that basal forebrain neurons selectively coded information about reinforcement and novelty-familiarity relations, and have strong plastic neuronal responses that are related to learning. Monkeys with basal forebrain deficits had impairment of some kind of learning and memory, such as new visual object learning, relearning object discrimination, and serial reversal learning. The basal forebrain receives neuronal inputs from many areas, including the inferotemporal and entorhinal cortices, amygdala, hippocampus, and lateral hypothalamic area. Detailed experimental procedures are described. Single unit activity from the monkey basal forebrain, including the nucleus basalis of Meynert and the diagonal band of Broca was recorded during a visual discrimination task to study the contribution of the basal forebrain to visual learning and memory related to novel and familiar objects. The task included discrimination of rewarding or aversive objects, novel and familiar objects, and association or dissociation with stimulus-reinforcement relations.

Odor-guided learning and memory in rats: is it ‘special’?

the first 20 trials of each problem after having learned no more than four such problems previously. Rapid progressive improvement is not a special feature of olfactory learning. There remains one feature of olfactory learning that might prompt us to allow it some special status, and ironically this is found in the work of Reid and Morris 3 themselves. It is their finding that serial reversal improvement fails to occur. Such improve- ment emerges quite readily when rats are trained on an analogous visual discrimination 3. One reason for this improvement, it has been suggested, is that the rats come to restrict attention to the relevant stimuli, to abandon position habits, and so on, an interpret- ation that makes Reid and Morris's failure to find the effect all the more puzzling since it is just these processes that they suggest might generate the improvement they observe in the olfactory learning-set procedure. I have no solution to this enigma. All I can do is express the hope that further research will clarify the issue of what conditions are necessary for serial reversal improvement in ol- factory learning; also, given the current state of confusion on this issue, to urge caution about taking the Reid and Morris result as a convincing demon- stration that olfactory learning is in some way special.

A specific form of cognitive rigidity following excitotoxic lesions of the basal forebrain in marmosets

The effects of N-methyl- d-aspartate-induced lesions of the basal forebrain were studied on performance of a series of visual discrimination tests that examined a range of cognitive functions in the marmoset. These included the ability to attend to the various dimensional properties of stimuli and to use just one of these properties in order to solve a discrimination (intra-dimensional shift); to switch attention from one dimension to another (extra-dimensional shift); to learn the reinforcement value of specific exemplars within a dimension (new learning); and to relearn their reinforcement value following reversal of the reward contingencies (serial reversals). Lesions of the basal forebrain did not impair the ability either to attend selectively to the dimensional properties of the stimuli or to switch attention from one dimension to the other. However, the lesion did affect various aspects of associative learning including a transient impairment of new learning and a marked disruption of serial reversal learning. The reversal deficit could be characterised as a tendency to perseverate on the previously correct stimulus and as a failure to to show the formation of a reversal learning set. In addition, the lesion prevented disruption of performance of a well-learned discrimination when novel exemplars from the irrelevant dimension were introduced (probe test). It is suggested that the functional effects of the basal forebrain lesion reflect impaired learning of stimulus-reward associations and behavioural rigidity. The finding, however, that there was no effect of the lesion on attentional set-shifting suggests that any loss of inhibitory control was specific to the level of stimulus-response or stimulus-reward associations, inhibitory control at the level of attentional selection remaining intact. The similarity of the effects of damage to the basal forebrain to those seen following damage to the orbitofrontal cortex and the amygdala are discussed in the context of the close anatomical and functional relationships that exist among these three structures.

Serial spatial reversal learning in rats: Comparison of instrumental and automaintenance procedures

Serial reversals of a spatial discrimination were trained in rats under automaintenance conditions, in which food reward occurred regardless of responding. This automaintained reversal learning was compared to instrumental reversal learning in other rats trained under a similar procedure which required responding for reward. In the automaintenance (AU) procedure, rats received food after every retraction of a “positive” response lever (S +); retraction of a second, “neutral” lever (S°) was not paired with food delivery. Responses to the S + were elicited at fairly constant rates during daily 100-trial conditioning sessions. Responses to the S° occurred early in each session but rapidly diminished across trials. When the valences of the levers were reversed, responding shifted to the new S + and diminished on the new S°. Criterion for reversal was defined as a discrimination ratio (DR) of at least 90% responding to the S + in two consecutive 10-trial blocks. With repeated reversals, acquisition of criterion performance occurred with increasing rapidity, reaching an asymptote below that required for the original discrimination. A second group of rats was trained on a similar instrumental schedule, in which at least one response to the S + was required for food delivery. Response rates in this instrumental (IN) group were approximately double those of the AU group. However, ratios of S + to S° response rates were similar to those of the AU group, and the serial reversal curves generated were qualitatively similar. Thus rats can show improvement across serial reversals of a spatial discrimination based entirely on pairings of stimulus events (automaintenance), in a manner similar to that observed in instrumental procedures, in which reward is contingent upon correct responding.

Behavioural rigidity and rule-learning deficits following isolation-rearing in the rat: neurochemical correlates

Isolation-reared rats were compared to those reared in social groups on the acquisition of a conditional visual discrimination (Expt. I), a simultaneous (simple) light/dark discrimination and serial reversal learning (Expt. II). In Expt. I, rats reared in social isolation made more errors during the acquisition of the conditional discrimination but did reach a level of accurate performance which was comparable with that of socially-reared rats. Discrimination performance in isolates was less disruptable by manipulations of the task requirements. Reducing the number of stimulus lights or the introduction of a distracting stimulus increased the number of errors committed by socially-reared rats but did not significantly affect accuracy in isolates. Performance in isolated rats was also remarkably resistant to changes in motivational variables. Isolates responded more frequently during conditions of extinction and were virtually unaffected by pre-feeding prior to testing. In Expt. II, isolation-reared rats were not impaired in the acquisition of a simultaneous discrimination but unlike socially-reared rats isolates failed to show improvement with successive reversals of this discrimination. Isolates exhibited stronger position habits than socially-reared rats following reversal of the contingencies. These results of these two experiments combined have demonstrated a specific impairment in rule learning in isolates. Isolated rats were not impaired on a simultaneous discrimination in which accurate performance can be achieved simply by approaching the stimulus associated with reinforcement, but performed worse than controls on both the conditional discrimination and on serial reversal learning, another form of conditional task. In both of these latter tasks each stimulus becomes equally associated with reward and therefore performance can be improved by learning a rule. Post-mortem neurochemical measurements made at the completion of Expt. II revealed selective alterations in dopaminergic, serotoninergic and cholinergic markers in isolated rats. Correlational analyses indicated specific relationships between neurochemical and behavioural measurements.

Impairment of olfactory, auditory, and spatial serial reversal learning in rats recovered from pyrithiamine-induced thiamine deficiency.

Impairment of olfactory, auditory, and spatial serial reversal learning in rats recovered from pyrithiamine-induced thiamine deficiency.

Impairment of olfactory, auditory, and spatial serial reversal learning in rats recovered from pyrithiamine-induced thiamine deficiency.

Rats that had recovered from pyrithiamine-induced thiamine deficiency (PTD) were compared with controls for spatial, auditory, and olfactory serial reversal learning (SRL); spatial matching to sample (MTS); auditory go-no-go discrimination; and open-field exploration. PTD rats made more errors reaching criterion for SRL in all modalities but showed normal transfer effects between problems. PTD rats were also impaired in learning the go-no-go and MTS tasks and showed consistent alterations in exploratory activity. It is argued that the PTD rat, like human Korsakoff patients, have impairments of learning and memory (but spared capacity for reference memory) that extend across sensory modalities. Postmortem analyses showed normal indices of cortical cholinergic, noradrenergic, dopaminergic, and serotonergic function and consistent bilateral lesions of the thalamus, which were centered on the internal medullary lamina, and the medial mammillary nucleus.

Effects of physostigmine on operant serial discrimination/reversal learning in rats

Two experiments examined the effects of physostigmine on acquisition and performance of operant serial reversals by rats. In Experiment 1, four groups of rats (n = 6/group) were injected with either vehicle or 0.03 mg/kg physostigmine five minutes prior to each session, or vehicle or 0.5 mg/kg physostigmine immediately after each session of a three-stimulus (bright, dim or flashing light) repeated discrimination/reversal procedure. Rats treated with physostigmine pre- or postsession learned significantly more reversals over 50 sessions than animals injected with vehicle. Experiment 2 used only two discriminative stimuli, a light and a 2,500 Hz tone. Following establishment of a stable daily reversal baseline, postsession injections of physostigmine significantly increased the number of trials to criterion on the next session compared to each subject's control baseline. Results are attributed to enhanced between-session transfer of previously learned discriminated instrumental responses by physostigmine-treated animals.

Repeated exposure to diisopropylfluorophosphate (DFP) produces increased sensitivity to cholinergic antagonists in discrimination retention and reversal

This experiment examined the effects of repeated exposure to diisopropylfluorophosphate (DFP), an organophosphate anticholinesterase, on the retention and reversal of a visual discrimination and on the number of muscarinic receptors in the brain. Rats were trained in a serial reversal procedure. After achieving stable performance, the rats were divided into two groups. One group received repeated injections of DFP, the other group received injections. To determine whether DFP-treated rats would be more sensitive than normal rats to stresses on the cholinergic system, each rat was injected with saline or one of three doses of scopolamine, a muscarinic receptor blocker, prior to testing on every 6th day. DFP alone caused no impairment in performance. Scopolamine produced a greater impairment in DFP-treated rats than in control rats. Similar results were obtained in a second behavioral task, match-to-sample in a water maze, using the same DFP treatment protocol and only one dose of scopolamine. The number of muscarinic receptors and acetylcholinesterase activity levels were reduced on the 2nd and 15th day after the end of DFP treatment. These results demonstrate that although repeated exposure to organophosphate anticholinesterases may not alter discrimination behavior directly, it may compromise the central nervous system so that it cannot react normally when challenged.

The effects of excitotoxic lesions of the basal forebrain on the acquisition, retention and serial reversal of visual discriminations in marmosets

The effects ofN-methyl- d-aspartate-induced lesions of the basal forebrain (which included the cholinergic cells of the nucleus basalis of Meynert) were studied on three aspects of visual discrimination; learning, retention and reversal performance, in the marmoset. Neurobiological investigations revealed that the lesion produced large reductions in choline acetyltransferase activity within anterior regions of cortex, particularly prefrontal. In Experiment 1 lesioned animals showed impaired retention, one week after surgery, of a visual discrimination learned immediately prior to surgery and subsequently showed impaired performance over a series of reversals. The reversal deficit could be characterized as a tendency to perseverate on the previously correct stimulus on the first reversal and as a failure to show serial reversal learning on subsequent reversals. Acquisition of a novel discrimination was not impaired five weeks after surgery. As time of testing may have been a confounding factor, in Experiment 2 the effects of the same lesion on new learning were examined immediately following surgery and the effects on retention a month later. The lesion was found to disrupt new learning but did not affect retention. From the two experiments it is clear that, whereas disruption of retention and new learning was relatively transient, the impairments in reversal performance were more long lasting. In addition, lesioned animals exhibited behavioural hyperactivity and elevations in consummatory and schedule-controlled licking. The disinhibitory and perseverative effects observed following lesions of the basal forebrain in this study are similar to those following lesions of the orbitofrontal cortex while the disruption of serial reversal learning is commonly seen following damage to the amygdala. Therefore, these results are consistent with the hypothesis that the range of behavioural effects of the lesion result from damage to the cholinergic afferents to orbitofrontal cortex and to the amygdala, two structures intimately connected to one another.

Effects of arecoline and pilocarpine on learning ability in marmosets pretreated with hemicholinium-3.

Common marmosets (Callithrix jacchus) were trained to perform serial reversal position discrimination tasks in a Wisconsin General Test Apparatus. Intraventricular injection of hemicholinium-3 4 h before testing resulted in a profound impairment of position discrimination learning which could be overcome by the intramuscular administration of low doses of the muscarinic agonists, arecoline or pilocarpine.

Double dissociation of effects on learning of medial versus lateral hyperstriatal lesions in pigeons.

Three experiments examined the effects of medial and lateral hyperstriatal lesions in two groups of pigeons. In Experiment 1, both hyperstriatal groups were impaired, relative to unoperated and operated control groups, in postoperative performance of preoperatively acquired serial reversal of both spatial and visual discriminations. The deficits of the two hyperstriatal groups appeared both quantitatively and qualitatively similar. Experiment 2 found that performance of spatial reversals was disrupted in the medial, but not in the lateral, hyperstriatal group by a long intertrial interval. Experiment 3 found that acquisition of simultaneous matching-to-sample was disrupted by lateral, but not by medial, hyperstriatal lesions; the lateral group also showed a lower rate of response to the sample stimulus than any of the other groups. Implications of these findings for current theories of hyperstriatal function are discussed.

Effects of ibotenic acid lesions of the basal forebrain on serial reversal learning in marmosets.

Five common marmosets (Callithrix jacchus) received unilateral ibotenic acid lesions of the basal forebrain. Seven days post-operatively, choline acetyltransferase activity was reduced by 60% in frontal cortex and 40% in temporal cortex in the ipsilateral side compared with the contralateral side. Four animals receiving bilateral lesions of the same area were impaired on the first post-operative task of serial reversal learning when compared with four animals receiving bilateral saline injections. Although their performance improved with time, the lesioned animals were subequently impaired following administration of a low dose of scopolamine which did not affect the control group. These results show that lesions within the basal forebrain can affect cholinergic function in the cortex and impair learning ability.

Differences in mechanisms of intelligence among vertebrates

Much comparative research aimed at establishing differences in intelligence among vertebrates has failed to convince the sceptic, because it has concentrated on a single experimental paradigm (such as learning sets), while employing a diverse array of species in the hope of establishing a rank ordering of intelligence. The sceptic can insist that such research has not even established that there are any differences in mechanisms of intelligence between any pair of vertebrate species, let alone elucidated the nature of the difference, and even the unsceptical will doubt that such research is ever likely to establish a rank order of intelligence. It is more informative to concentrate on fewer species, but a broader range of experimental paradigms. Thus, studies of serial reversal learning have consistently suggested that goldfish do not show such rapid improvement as do rats. One explanation of this might be that rats learn more effectively than goldfish to use the outcome of one trial to predict the outcome of the next. The suggestion is supported by finding other experimental paradigms, such as alternation learning, which must also tap such a process, and where rats again learn more rapidly than goldfish. Efficient learning-set performance may also depend on this process, but must in addition require the subject to transfer this rule across changes of stimuli. There is reason to believe that not all vertebrates are equally adept at such transfer, and this possibility is explored in a series of experiments studying the transfer of matchingto-sample in pigeons and corvids. The corvids display significantly better transfer and the close similarity in training procedures possible with these subjects makes it unlikely that this is due to differences in these training procedures.

Cortical cholinergic impairment and behavioral deficits produced by kainic acid lesions of rat magnocellular basal forebrain.

The magnocellular basal forebrain (MNBF) provides extensive cholinergic innervation to frontoparietal cortex. In the rat, the MNBF is homologous to the human nucleus basalis of Meynert, a structure implicated in the cholinergic hypothesis of cognitive impairment in Alzheimer's disease (AD). Kainic acid (KA) was used to make lesions in the MNBF of rats which were compared with unoperated controls, sham-operated controls, and control rats injected with KA in the cortical area directly above the MNBF. The MNBF lesions depleted choline acetyltransferase in cortex but not in striatum or hippocampus. Cortical dopamine levels were unchanged; serotonin levels were unchanged in hippocampus and parietal cortex but decreased in frontal cortex. The metabolite levels of these neurotransmitters were unchanged in all brain regions examined. Compared with controls, rats with MNBF lesions were impaired in 24-hr retention, but not acquisition, of a passive avoidance task with escapable footshock. There were no differences between groups in mean number of daily avoidances on a bar-press active avoidance task, although the data suggested a slower rate of learning in MNBF rats. In a serial spatial discrimination reversal test with a snout-poke response, the MNBF rats performed significantly worse than controls, although all groups learned the task. This rodent model is useful for studying the role of the cholinergic system in memory and possibly for developing treatment strategies to alleviate the cognitive dysfunction of AD.

Reversal learning by fornix-transected monkeys.

Experiment 1 examined visual reversal learning and in Experiment 2 monkeys were trained to criterion in a serial reversal set between “FR” and “DRO” response requirements. In both cases impairments were observed in fornix-transected monkeys. These results are discussed in connection with previous findings that in serial reversals damage to the hippocampal system in monkeys causes a deficit in spatial but not in visual learning. A unified account is proposed.