An analysis of reversal learning in relation to the complexity of task in white rats.
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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.
The effect of a low dose (3 micrograms/kg) of medetomidine on cognitive performance of aged rats was examined in position discrimination and reversal learning in a T-maze. In Experiment 1, the reversal was introduced after 3 days of position habit acquisition and in Experiment 2 in the same session. Open-field and novelty-suppressed feeding tests were undertaken before drug testing to relate the cognitive effect of medetomidine with exploratory activity and neophobia of individual rats. Medetomidine slightly impaired the acquisition of position discrimination in both sexes and decreased perseveration in the reversal of a well-established position habit in females. The correlation of these findings with exploratory activity and neophobia is discussed.
A conservative eutherian mammal (the hedgehog, Paraechinus hypomelas) was tested on delayed alternation performance and spatial reversal learning before and after ablations of the prefrontal cortex. The anatomical results show that the cortical focus of the projections of the medial dorsal nucleus, the prefrontal cortex, does not include the neocortex on the dorsal convexity of the hedgehog's frontal lobe but, instead, the perirhinal and pregenual neocortex immediately surrounding the frontal convexity. The behavioral results show that normal performance of hedgehogs on these two behavioral tests depends upon the integrity of their prefrontal cortex, but not on the integrity of their frontal convexity or olfactory bulbs. The similarity in the results obtained from prefrontal hedgehogs and a divergent variety of other species with prefrontal ablations indicates that the role of the prefrontal system in the abilities measured by these two tests is at least as old as Eutheria and, thus, probably imposed persistent constraints on subsequent evolutionary modifications of the prefrontal system.
The effects of excitotoxic lesions of the mediodorsal nucleus of the thalamus, the anterior thalamic nuclei and of the prelimbic cortex were examined on two tests of discrimination and reversal learning. In experiment 1A (visual discrimination and reversal), rats were required to discriminate two stimuli, and respond to the stimulus associated with reward (the S+ stimulus). There was no effect of lesion on acquisition of this task. However, when stimulus-reward contingencies were reversed, animals with lesions of the mediodorsal nucleus of the thalamus made significantly more errors than control animals or animals of other lesion groups. In experiment 1B (conditional discrimination), animals were required to learn a rule of the type 'If stimulus A then go left, if stimulus B then go right'. No main effect of lesion on acquisition was observed in this experiment. To test the generality of the reversal effect obtained in experiment 1A, a second cohort of animals with the same lesions was tested on acquisition of the visuospatial conditional task immediately postsurgery, followed by the reversal of the conditional rule (experiment 2). As in experiment 1B, no main effect of lesion group was observed during acquisition of the task. However, lesions of the mediodorsal nucleus of the thalamus resulted in a mild impairment according to number of sessions required to attain criterion performance of the task when the response rule was reversed. The results of the present study provide evidence for a role for the mediodorsal nucleus of the thalamus in new learning, particularly when stimulus-reward contingencies are reversed. Furthermore, they show that the functions of this thalamic nucleus can be dissociated from those of the anterior thalamus and the prelimbic cortex.
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.
The effects of bilateral lesions of individual laminae of the Wulst on reversal-learning performance in pigeons were evaluated. After surgery, the birds were trained to perform a simultaneous color discrimination. Once successful discrimination was achieved, the positive and negative stimuli were reversed, and the birds were again trained to criterion. Twenty such reversals were carried out. A multiple regression analysis indicated that those components of the Wulst that were critical for increasing the numbers of errors on each reversal were the laminae that receive the thalamofugal visual projections, that is, the nucleus intercalatus of the hyperstriatum accessorium and the hyperstriatum dorsale. Lesions in the other laminae of the Wulst (the hyperstriatum accessorium and the hyperstriatum intercalatus superior) had no effect on errors. There was no evidence of an increase in either perseverative errors or position habits in the birds with lesions, which suggested that the reversal deficits were not likely to be due to perseveration, attentional impairment, or inappropriate processing of spatial information. The deficit may have been produced by excessive interference between learning in a given session and learning in previous sessions.
The effects of prefrontal medial or lateral lesions on the retention of avoidance go no go click-tone differentiation in dogs were studied. The acquisition of the differentiation was influenced by the quality of the stimuli since more errors were performed to the click CS(-) than to the tone CS(-). Neither medial nor lateral lesions exerted any effect on retention of the differentiation. Similarly, as during original differentiation training, the quality of the stimuli had an effect on reversal learning in normal dogs. Such an effect was markedly reduced in dogs with prefrontal lesions and more strongly in those Ss which received lateral lesions. The results were discussed relative to data obtained from cats trained under similar conditions. The dogs showed better responding on positive trials while performance in cats was better on negative trials. The stimulus quality effect was more pronounced in dogs during negative, and in cats during positive trials.
In 3 human predictive learning experiments, the authors examined contextual control of responding in discrimination reversal learning. In Phase 1, a discrimination between 2 stimuli (A+, B-) was trained in Context 1. During Phase 2, participants received discrimination reversal training (A-, B+) in Context 2. Testing occurred in Context 1 and Context 2 (Experiments 1A and 1B) or in Context 1 and Context 3 (Experiment 2). During the test phase, performance in Context 1 and Context 2 reflected the contingencies trained during Phase 1 and Phase 2, respectively. When testing occurred in Context 3, there was no discriminative responding between A and B. In addition, the experiments demonstrated that discriminating stimuli with a consistent reinforcement history were also affected by contextual manipulations. Results indicate that each training context acquires the ability to control performance. Unique-cue and configural approaches account for a major part of the results.
The current study was conducted to examine the performance of mice with a targeted deletion of the gene for DARPP-32 in a discriminated operant task using food reinforcement. DARPP-32 plays a central role in regulating the efficacy of dopaminergic neurotransmission. Initially, wild-type and DARPP-32 knockout mice were trained to nose-poke for food on a continuous reinforcement schedule. The minimum response requirement was increased every 5 days until the animals were responding on an FR-15 schedule of reinforcement. At the completion of extensive operant training, reversal learning was assessed. Wild-type and DARPP-32 knockout mice exhibited equivalent performance during acquisition of this task, with both groups increasing operant responding as the schedule of reinforcement was raised. However, significant differences in discrimination learning were observed during the reversal phase, with DARPP-32 knockout mice requiring significantly more trials to reach criterion than wild-type controls. These results provide evidence for a functional role of DARPP-32 in the mediation of processes underlying learning and memory.
A total of 118 subjects, divided into high scoring 129/J and low scoring DBA/1J parents, F2, and reciprocated F1, B1, and B2 generations, were given reversal training for 50 sessions. Results showed that the parent strain providing genes that were more favorable to reversal learning provided a maternal environment that was significantly less favorable than that provided by the other parent strain. There was also found to be significant nonalletic interaction, a genetic factor the presence of which had not been suggested by the results of earlier work using the diallel cross method.
The availability of pluripotent embryonic stem (ES) cells for gene targeting has resulted in laboratory mice becoming important animal models of human neurological disease. Inbred strains of mice differ in many behavioural phenotypes, such that the same gene mutation can appear to have different phenotypic effects when introduced onto different genetic backgrounds. Prior knowledge of the behavioural phenotypes of the inbred strains used for gene targeting would, therefore, allow the selection of the most appropriate genetic background for the hypothesis to be tested. With this in mind, we tested eight strains of mice (129S1/SvImJ, 129S2/SvPasIcoCrlBR, 129S6/SvEvTac, B6129SF1/J, C57BL/6J, C57BL/6N, LP/J and SM/J), including the sources of five ES cell lines commonly used for gene targeting, in the spatial (submerged platform) version of the Morris water maze, the most widely used paradigm to evaluate the cognitive abilities of genetically modified mice. The three 129 substrain sources of ES cell lines demonstrated spatial learning in the water maze that was superior to that of C57BL/6J, the inbred strain most commonly used for the maintenance and phenotypic testing of mutations. In addition, 129S6/SvEvTac was unique amongst the eight strains tested in having a particular capacity for reversal learning, when the submerged platform was relocated to the opposite quadrant. We conclude that some substrains of 129 could provide suitable genetic backgrounds for testing gene mutations that might be expected to impair cognitive function, thus negating the need to backcross to C57BL/6J, thereby avoiding the so-called "flanking gene problem".
Many comparative pieces of research support the hypothesis that the medial cortex region of the reptilian forebrain could be homologous to hippocampal formation. Besides, there is some evidence involving this structure in complex spatial learning in a similar manner to hippocampus of mammals and birds. In this experiment we examined effects of medial cortex lesion in reversal learning. Turtles were trained in a spatial and a non-spatial maze procedure and the reversal of these tasks. Data revealed that sham and medial cortex lesioned turtles of both procedures performed well on the initial learning (acquisition). However, during the reversal phase, only the turtles with medial cortex lesion showed impaired performance in the spatial procedure. These results suggest that turtles possess different spatial learning and memory systems in close parallel to those described in other vertebrates, and that medial cortex plays a crucial role in complex place learning.
The olfactory thalamocortical system was disrupted bilaterally in rats using (a) unilateral mediodorsal thalamic (MD) lesions plus contralateral bulbectomy and transection of the anterior commissure (AC), (b) unilateral MD lesions plus contralateral lesions of the frontal cortex, or (c) bilateral MD lesions. Rats were trained on an odor discrimination task and on the reversal of that task. Experimental groups performed as well as controls on the initial discrimination task but made more errors on the reversal problem. Rats with asymmetrical disruption of the olfactory thalamocortical system performed as poorly as those with bilateral MD lesions. These outcomes indicate that odor reversal learning deficits in rats with bilateral MD lesions stem from interruption of the olfactory thalamic-neocortical system and also provide evidence that the AC mediates significant interhemispheric transfer of olfactory information.
Rab proteins are small GTPases involved in intracellular trafficking. Among the 60 different Rab proteins described in mammals, Rab3a is the most abundant in brain, where it is involved in synaptic vesicle fusion and neurotransmitter release. Rab3a constitutive knockout mice (Rab3a(-/-)) are characterized by deficient short- and long-term synaptic plasticity in the mossy fiber pathway and altered circadian motor activity, while no effects on spatial learning have been reported so far for these mice. The goals of this study were to analyse possible behavioral consequences of the lack of synaptic plasticity in the mossy fiber pathway using a broad battery of sensitive behavioral measures that has been used previously to analyse the behavior of Gdi1 mice lacking a protein thought to regulate Rab3a. Rab3a(-/-) mice showed normal acquisition but moderately impaired platform reversal learning in the water maze including reference memory and episodic-like memory tasks. A mild deficit in spatial working memory was also observed when tested in the radial maze. Analysis of explorative behavior revealed increased locomotor activity and enhanced exploratory activity in open field, O-maze, dark/light box and novel object tests. Spontaneous activity in normal home cage settings was unaffected but Rab3a(-/-) mice showed increased motor activity when the home cage was equipped with a wheel. No differences were found for delayed and trace fear conditioning or for conditioned taste aversion learning. Congruent with earlier data, these results suggest that Rab3a-dependent synaptic plasticity might play a specific role in the reactivity to novel stimuli and behavioral stability rather than being involved in memory processing. On the other hand, the phenotypic changes in the Rab3a(-/-) mice bore no relation to the behavioral changes as observed in the Gdi1 mice. Such divergence in phenotypes implies that the putative synaptic interaction between Gdi1 and Rab3a should be reconsidered and re-analysed.
One prediction of the hypothesis that the capacity for hippocampal frequency potentiation is relevant to behavioral plasticity is tested in this study, by chronically elevating magnesium in intact aged and young rats. Elevated extracellular Mg2+ specifically improves frequency potentiation in hippocampal slices, and chronic alterations in plasma Mg2+ can increase brain Mg2+ in intact animals. Aged and young rats on a diet that elevated plasma Mg2+ exhibited stronger frequency potentiation under urethane anesthesia, and showed improved maze reversal learning.
Rats with either electrolytic medial septal lesions or cytotoxic entorhinal lesions were compared to unoperated controls on a series of delayed matching-to-sample (DMS) tasks. A DMS trial consisted of two runs. In the first (information) run, the subject was familiarized with a sample discriminandum. In the second (choice) run, the subject was required to discriminate the sample discriminandum from a novel one. When a set of 20 discrete complex objects were used as discriminanda and each discriminandum was used once per day, neither lesions impaired choice accuracy. However, when a single pair of simple discriminanda was employed and re-used between trials within a day, rats with medial septal lesions were severely impaired whereas rats with entorhinal lesions performed at a level comparable to unoperated controls. Next, proactive interference was demonstrated by the introduction of an extra run prior to the information run. When this extra (pre-information) run required the subjects to visit the (eventual) negative discriminandum such that correct choice had to be guided by relative familiarity judgement, choice performance was reduced. Neither lesion group was selectively affected by this manipulation. But when the relative reinforcement history of the pre-information run and the information run was manipulated, such that a correct response required the subject to approach a discriminandum that had recently been non-rewarded, rats with entorhinal lesions were selectively impaired. The effect of delay was demonstrated when a 20-s interval was imposed between information run and choice run. This reduced overall choice accuracy, and this effect appeared to be more pronounced in both lesion groups, although not significantly so. Finally, neither lesion affected the acquisition of a simple discrimination task, but reversal learning was selectively enhanced in the entorhinal lesion group.
Pregnant mice were fed equivalent daily amounts of a liquid diet containing 25% (kcal) ethanol, or with maltose dextrin substituted isocalorically for ethanol. In addition, the diet contained 20% oil; this was either of two mixtures, one comprised of predominantly n-6 (18:2n-6) fatty acids, and the other containing an equivalent amount of n-6, but supplemented with a source of long chain n-3 (20:5n-3, 22:6n-3) fatty acids. An additional control group was fed lab chow ad libitum. The treatment was implemented from day 7 to 17 of gestation, whereafter all groups were fed lab chow. Ethanol decreased maternal weight gain and pup body and brain weight; it also retarded both sensory and motor development in the pups and impeded reversal learning in a water maze. The n-3 supplementation lowered maternal blood alcohol concentration, but counteracted only some of the effects of ethanol, by increasing maternal weight gain and pup body weight, and also by enhancing sensory development in the pups. Such effects were additive, in that they were also present in the maltose-dextrin control group. These findings suggest that n-3 supplementation may ameliorate some of the effects of ethanol on neurobehavioral development, but the magnitude of the effect appears to be small.