An evaluation of transfer suppression phenomenon at different stages of learning-set formation

Three groups of three rhesus monkeys each trained to varying levels of object discrimination learning-set formation were tested for reversal-learning proficiency. Training consisted in presenting discrimination problems by the usual learning-set procedure; whereas reversal-learning proficiency was tested by presenting the reversal problems along with control problems according to the usual learning-set procedure and also according to the serial learning procedure. No substantial change in negative interproblem transfer effects was observed as a result of learning-set proficiency, as reversed-problem performance remained significantly poorer than control-problem performance at all the levels. Learning of a reversed problem was not found to be in any way related to anS's correct or incorrect response on its first acquisition trial.     

Acquisition of an olfactory learning-set in rats with lesions of the mediodorsal thalamic nucleus

Rats with lesions of the mediodorsal thalamic nucleus had goodretention of a preoperatively leamed odor detection task butmade more errors than controls in the acquisition of a seriesof two-odor discrimination problems. While controls showed rapidacquisition of a learning-set, the performance of experimentalrats was highly variable. Deficits in acquisition occurred ondifferent problem for different rats and appeared unrelatedto problem difficulty or serial position of the discrimination.Experimental rats also had a significant deficit in the acquisitionof an odor reversal task. Error scores in both the learing-setand reversal task were related to lesion size. Small lesionsconfined to the rostral third of the nucleus or asymmetricallesions which spared the central (olfactory) division of mediodorsalnucleus on one side were without effect. The results suggestthat the deficit in olfactory learning produced by destructionof the mediodorsal thalamic nucleus is complex and is not adequatelyaccounted for by stimulus novelty, problem difficulty or bypoor interproblem transfer of learning.     

Performance correlates of social behavior and organization: Social rank and complex problem solving in crab-eating macaques (M. fascicularis)

Seventeen male crab-eating macaques, drawn from two captive troops, were tested on a series of complex problem solving tasks in a Wisconsin General Test Apparatus (wgta). The animals were trained on a series of 6-trial object quality learning set problems followed by a series of 10-trial object quality learning set problems. They were then given problems in which the correct stimulus object was reversed part way through the problem. After the animals reached criterion on this task, the reversal learning set was then extinguished. High ranking animals made more intraproblem errors than low ranking animals on the 6-trial problems, but there was no relationship between social status and the rapidity with which the object quality learning set was established. Animals that received overtraining on the 6-trial problems transferred their learning virtually intact to the 10-trial problems; however, high ranking animals without overtraining made more errors than low ranking animals. On reversal learning and reversal extinction, high ranking animals made more errors on critical trials, indicating that they formed and extinguished the reversal set more slowly than low ranking animals. Object quality sets, as measured by trial-2 performance, were not affected by the reversal conditions. Supported by USAMRDC Contract No. DADA 17-73-C-3007.     

Recording Single Neurons' Action Potentials from Freely Moving Pigeons Across Three Stages of Learning

While the subject of learning has attracted immense interest from both behavioral and neural scientists, only relatively few investigators have observed single-neuron activity while animals are acquiring an operantly conditioned response, or when that response is extinguished. But even in these cases, observation periods usually encompass only a single stage of learning, i.e. acquisition or extinction, but not both (exceptions include protocols employing reversal learning; see Bingman et al.¹ for an example). However, acquisition and extinction entail different learning mechanisms and are therefore expected to be accompanied by different types and/or loci of neural plasticity.Accordingly, we developed a behavioral paradigm which institutes three stages of learning in a single behavioral session and which is well suited for the simultaneous recording of single neurons'' action potentials. Animals are trained on a single-interval forced choice task which requires mapping each of two possible choice responses to the presentation of different novel visual stimuli (acquisition). After having reached a predefined performance criterion, one of the two choice responses is no longer reinforced (extinction). Following a certain decrement in performance level, correct responses are reinforced again (reacquisition). By using a new set of stimuli in every session, animals can undergo the acquisition-extinction-reacquisition process repeatedly. Because all three stages of learning occur in a single behavioral session, the paradigm is ideal for the simultaneous observation of the spiking output of multiple single neurons. We use pigeons as model systems, but the task can easily be adapted to any other species capable of conditioned discrimination learning.     

The learning skills of great apes

Through use of a refined measurement of learning-set capacity, a comparative study of 45 great apes, six gibbons, and representative monkey groups was conducted to determine the relationship between cortical evolution and cognitive skills. The measurement employed. termed the Transfer Index, entailed criterional achievement on each of a series of two-choice visual discrimination problems, then test trials in which the initial cue values were reversed. The pre-reversal criterional mastery served as an empirical basis for matching subjects of the diverse primate groups on a performance criterion prior to the procurement of the critical measures taken on the reversal trials to assess learning and transfer-to-training capabilities. The results reveal the following: (1) general superiority of the great apes over all other primate groups tested; (2) interactions between species, pre-reversal criterional level employed, and reversal performance; and (3) support for the conclusion that learning and transfer-of-training skills are positive correlates of cortical evolution.     

Sex chromosome complement affects multiple aspects of reversal-learning task performance in mice

Determining the mechanisms by which the sex-chromosome complement (SCC) affects learning, attention, and impulsivity has implications for observed sex differences in prevalence, severity, and prognosis of psychiatric/neurodevelopmental disorders and syndromes associated with sex-chromosome aneuploidy. Here, Four Core Genotypes (FCG) mice were evaluated in order to assess the separable and/or interacting effects of gonads (testes vs. ovaries) and their secretions and/or SCC (XX vs. XY) acting via non-gonadal mechanisms on behavior. We tested FCG mice on a reversal-learning task that enables the quantification of aspects of learning, attention and impulsivity. Across testing phases (involving the initial acquisition of a spatial discrimination and subsequent reversal learning), overall error rate was larger in XY compared with XX mice. Although XX and XY groups did not differ in the total number of trials required in order to reach a preset performance criterion, analyses of reversal error types showed more perseverative errors in XY than XX mice, with no difference in regressive errors. Additionally, prepotent-response latencies during the reversal phase were shorter in XY males, as compared with both XX gonadal males and females of either SCC, and failures to sustain the observing response were more frequent in XY mice than XX mice during the acquisition phase. These results indicate that SCC affects the characteristic pattern of response selection during acquisition and reversal performance without affecting the overall learning rate. More broadly, these results show direct effects of the SCC on cognitive processes that are relevant to psychiatric/neurodevelopmental disorders and syndromes associated with sex-chromosome aneuploidies.     

Pretraining and learning: Are “adaptable” monkeys “bright”?

Two groups of rhesus (Macaca mulatta),two groups of cynomolgus (M. fascicularis),and one group of stumptailed monkeys (M. arctoides)were adapted to testing in the Wisconsin General Test Apparatus using a standardized procedure that produced an objective measure of the speed of adaptation (pretraining). Four of the groups were then given standard object-discrimination learning-set training. The fifth group, one of the groups of rhesus monkeys, was given delayed response training before the learning-set training and delayed matching-to-sample learning-set training after. Only performance on the delayed response task was correlated with speed of pretraining. The results suggest that differences in pretraining performance reflect primarily emotional and/or temperamental differences, whereas differences in learning-set performance reflect primarily differences in cognitive functioning.     

über den Einfluß von Diäthylstilboestrol und anderer Wirkstoffe auf den Stoffwechsel männlicher Ratten

The presented study aimed at investigating the residual feed intake (RFI) of Sahiwal calves, nutrient utilisation as affected by RFI and its relationship with methane (CH₄) emissions and some blood metabolites. Eighteen male Sahiwal calves (10–18 months of age; mean body weight 133 kg) were fed ad libitum with a total mixed ration. After calculating RFI for individual calves (?0.40 to +0.34 kg DM/d), they were divided into three groups with low, medium and high RFI, respectively. Dry matter intake (DMI) was higher (p < 0.05) in Group High RFI, whereas digestibility of all nutrients except crude protein and ether extract was significantly higher in Group Low RFI. Nitrogen balance was also significantly higher in Group Low RFI (20.2 g/d) than in Group High RFI (17.0 g/d). Average daily gain and feed conversion ratio were similar among the groups. With exception of glucose, concentrations of all measured blood metabolites were higher in Group High RFI (p < 0.05). Compared with Group High RFI, the CH₄ emission of Group Low RFI was significantly lower (on the basis g/d and g/kg DMI by 11% and 19%, respectively). Furthermore, the CH₄ emission [g/d] was significantly correlated with RFI (r = 0.77). Because higher feed efficiency and less CH₄ production were observed in Group Low RFI, it was concluded that RFI can be used as a measure of feed efficiency, which has a potential to select Sahiwal calves for lowered CH₄ emissions.     

Evaluation of the effectiveness of intrauterine treatment with formosulphathiazole of clinical endometritis in postpartum dairy cows

In cattle, elimination of bacterial contamination from the uterine lumen after parturition is often delayed or compromised, and pathogenic bacteria can persist, causing uterine disease and infertility. The aim of this study was to compare the clinical and bacteriologic recovery following a single intrauterine administration of formosulphatiazole, cephapirin or placebo in cows with clinical endometritis. Cows (n = 80), no less than 28 days postpartum, with clinical endometritis were enrolled in the study. Endometritis was diagnosed by a complete reproductive examination, including rectal palpation, ultrasonography, vaginoscopy and uterine swab. All cows were randomly assigned to receive one of three intrauterine treatments (T0): 2500 mg of formosulphatiazole (Group A); 500 mg of cephapirin (Group B); placebo (4250 mg of propylene glycol; Group C). Cows were examined at the first estrus after treatment or no more than 30 days after (T1). Bacteria isolated were E. coli, A. pyogenes, Pasteurella spp. and Streptococcus spp. After treatment, in Group A and B only 6/30 (20.0%) and 6/24 (25.0%) cows showed a positive bacteriologic culture (P > 0.05), while in Group C the number of positive animals was significantly higher (19/26; 73.1%; P < 0.05). At T0, total clinical scores were similar between the three groups (Group A: 5.84 ± 1.07; Group B: 5.91 ± 1.0; Group C: 5.62 ± 1.17; P > 0.05) and indicative of clinical endometritis. At T1, endometritis scores were significantly lower than those reported before uterine infusion (P < 0.05); however, Group A and B score, 0.4 ± 0.9 and 1.0 ± 2.1, respectively, correspond to no and slight endometritis, while animals in Group C reported a total endometritis score significantly higher (4.6 ± 3.5; P < 0.05) corresponding to endometritis. In the present study, a commercial formosulphatiazole preparation was as effective as cephapirin and more effective than placebo for the treatment of clinical endometritis.     

Operant Procedures for Assessing Behavioral Flexibility in Rats

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these processes is the ability to adjust behavior in response to changes in one’s environment (i.e., behavioral flexibility). These processes are essential to normal human behavior, and may be disrupted in diverse neuropsychiatric conditions, including schizophrenia, alcoholism, depression, stroke, and Alzheimer’s disease. Understanding of the neurobiology of executive functions has been greatly advanced by the availability of animal tasks for assessing discrete components of behavioral flexibility, particularly strategy shifting and reversal learning. While several types of tasks have been developed, most are non-automated, labor intensive, and allow testing of only one animal at a time. The recent development of automated, operant-based tasks for assessing behavioral flexibility streamlines testing, standardizes stimulus presentation and data recording, and dramatically improves throughput. Here, we describe automated strategy shifting and reversal tasks, using operant chambers controlled by custom written software programs. Using these tasks, we have shown that the medial prefrontal cortex governs strategy shifting but not reversal learning in the rat, similar to the dissociation observed in humans. Moreover, animals with a neonatal hippocampal lesion, a neurodevelopmental model of schizophrenia, are selectively impaired on the strategy shifting task but not the reversal task. The strategy shifting task also allows the identification of separate types of performance errors, each of which is attributable to distinct neural substrates. The availability of these automated tasks, and the evidence supporting the dissociable contributions of separate prefrontal areas, makes them particularly well-suited assays for the investigation of basic neurobiological processes as well as drug discovery and screening in disease models.     

Performance correlates of social behavior and organization: Social rank and reversal learning in crab-eating macaques (M. fascicularis)

Seventeen male crab-eating macaques drawn from two captive troops, were tested on a brightness discrimination, reversal learning task. Fourteen of these animals completed ten reversals. It was found that the performance of the three highest ranking animals from each troop, taken together, was poorer than that of the lower ranking animals that were tested. The high ranking animals made more errors before reaching criterion on both initial learning and the reversal problems. Analysis of error patterns revealed that, while the high ranking animals had no more difficulty than the others in withholding their responses to the previously correct stimulus following reversals, they did not adopt the correct strategy as soon as the low ranking animals. The results have been interpreted in terms of a carry-over of a hypothetical factor or factors resulting from pressures created by the ongoing social dynamics involved in establishing and maintaining a given social rank at the time laboratory testing occurred. Supported by USAMRDC Contract No. DADA 17-73-C-3007.     

Dissociable Effects of 5-HT2C Receptor Antagonism and Genetic Inactivation on Perseverance and Learned Non-Reward in an Egocentric Spatial Reversal Task

Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT_2C receptor (5-HT_2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT_2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT_2CR antagonist SB242084 (0.5 mg/kg) in a between-groups serial design and Experiment 2 used 5-HT_2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS−), in a T- or Y-maze configuration. This was followed by three conditions; (1) Full reversal, where contingencies reversed; (2) Perseverance, where the previous CS+ became CS− and the previous CS− was replaced by a novel CS+; (3) Learned non-reward, where the previous CS− became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT_2CR KO mice showed increased perseverance. 5-HT_2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT_2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT_2CR antagonism and constitutive loss of the 5-HT_2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT_2CR loss on the development and maintenance of cognitive function.     

Social isolation improves working memory at reversal but not primary radial-arm maze learning in rats

Social isolation starting from the 21st day of birth affected neither a short-term nor a long-term memory in male rats at primary acquisition learning in an 8-arm radial maze. A number of the short-term and long-term memory errors were substantially decreased during primary learning but the difference between groups was not significant. Isolates were faster to start a search in an individual trial and took less time to finish offa trial. During the reversal learning, when baited and non-baited arms were reversed, the isolates outperformed of socially reared rats on working but not reference memory task. In overall they made twice less working memory errors than socially reared animals. During the reversal learning the isolates were also faster than non-isolates in initiation and completion of a trial. Maternal separation of rat's pups on the postnatal days 1-21 for 4 hr per day did not affect either working or reference memory on both primary and reversal learning. The data obtained are discussed on basis of influence of stress in early postnatal life on hypothalamo-pituitary axis and its effects on behavior of adult animals.     

A comprehensive analysis of translational missense errors in the yeast Saccharomyces cerevisiae

The process of protein synthesis must be sufficiently rapid and sufficiently accurate to support continued cellular growth. Failure in speed or accuracy can have dire consequences, including disease in humans. Most estimates of the accuracy come from studies of bacterial systems, principally Escherichia coli, and have involved incomplete analysis of possible errors. We recently used a highly quantitative system to measure the frequency of all types of misreading errors by a single tRNA in E. coli. That study found a wide variation in error frequencies among codons; a major factor causing that variation is competition between the correct (cognate) and incorrect (near-cognate) aminoacyl-tRNAs for the mutant codon. Here we extend that analysis to measure the frequency of missense errors by two tRNAs in a eukaryote, the yeast Saccharomyces cerevisiae. The data show that in yeast errors vary by codon from a low of 4 × 10⁻⁵ to a high of 6.9 × 10⁻⁴ per codon and that error frequency is in general about threefold lower than in E. coli, which may suggest that yeast has additional mechanisms that reduce missense errors. Error rate again is strongly influenced by tRNA competition. Surprisingly, missense errors involving wobble position mispairing were much less frequent in S. cerevisiae than in E. coli. Furthermore, the error-inducing aminoglycoside antibiotic, paromomycin, which stimulates errors on all error-prone codons in E. coli, has a more codon-specific effect in yeast.     

Discrimination reversal learning reveals greater female behavioural flexibility in guppies

Behavioural flexibility allows an animal to adapt its behaviour in response to changes in the environment. Research conducted in primates, rodents and domestic fowl suggests greater behavioural persistence and reduced behavioural flexibility in males. We investigated sex differences in behavioural flexibility in fish by comparing male and female guppies (Poecilia reticulata) in a reversal learning task. Fish were first trained on a colour discrimination, which was learned equally rapidly by males and females. However, once the reward contingency was reversed, females were better at inhibiting the previous response and reached criterion twice as fast as males. When reward reversing was repeated, males gradually reduced the number of errors, and the two sexes had a comparable performance after four reversals. We suggest that sex differences in behavioural flexibility in guppies can be explained in terms of the different roles that males and females play in reproduction.     

Intrusiefouten bij geheugenonderzoek

Extra-list intrusion errors during five trials of the eight-word list-learning task of the Amsterdam Dementia Screening Test (ADST) were investigated in 823 consecutive psychogeriatric patients (87.1% suffering from major neurocognitive disorder). Almost half of the participants (45.9%) produced one or more intrusion errors on the verbal recall test. Correct responses were lower when subjects made intrusion errors, but learning slopes did not differ between subjects who committed intrusion errors and those who did not so. Bivariate regression analyses revealed that participants who committed intrusion errors were more deficient on measures of eight-word recognition memory, delayed visual recognition and tests of executive control (the Behavioral Dyscontrol Scale and the ADST-Graphical Sequences as measures of response inhibition). Using hierarchical multiple regression, only free recall and delayed visual recognition retained an independent effect in the association with intrusion errors, such that deficient scores on tests of episodic memory were sufficient to explain the occurrence of intrusion errors. Measures of inhibitory control did not add significantly to the explanation of intrusion errors in free recall, which makes insufficient strength of memory traces rather than a primary deficit in inhibition the preferred account for intrusion errors in free recall.     

Failure of rats to acquire a taste reversal learning set

Rats were trained using operant conditioning to discriminateeither 0.9% NaCl from 0.1% saccharin or 0.75% NaCl from 1% sucroseand were tested on a series of seven successive discriminationreversal problems. Most animals made many more errors on thefirst reversal than on original learning (negative transfer)and none demonstrated acquisition of a reversal learning set.These results, together with those of prior studies in thislaboratory, indicate that on reversal learning tasks the performanceof rats trained with taste cues is inferior to those trainedwith odors and is quantitatively and qualitatively similar tothose trained with visual or auditory cues. These results arein marked contrast to those obtained in respondent conditioningof aversions where taste cues are much more effective than olfactory,visual or auditory cues.     

Effect of piracetam, a nootropic agent, on discrimination learning deficits induced by parental undernutrition and environmental impoverishment in young rats

The study was conducted on 64 Charles Foster albino rats which were equally distributed into 8 even-matched groups, following a 2 x 2 x 2 factorial design by varying three independent factors at two levels: nutrition--normal and undernutrition, environmental--enrichment and impoverishment, and drug treatment--vehicle and piracetam (100 mg/kg, ip). Prenatal nutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/drug treatments were given during the postweaning period of the rat pups. The animals were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. The results indicate that undernutrition and environmental impoverishment significantly attenuated the original discrimination as well as the reversal discrimination learning. Piracetam treatment improved the learning performance of normally reared rats and also attenuated the original and reversal learning deficits induced by prenatal undernutrition and postnatal impoverishment. The results indicate that piracetam may be useful in memory deficits induced by malnutrition.     

Studies of translational misreading in vivo show that the ribosome very efficiently discriminates against most potential errors

Protein synthesis must rapidly and repeatedly discriminate between a single correct and many incorrect aminoacyl-tRNAs. We have attempted to measure the frequencies of all possible missense errors by tRNA, tRNA and tRNA. The most frequent errors involve three types of mismatched nucleotide pairs, U•U, U•C, or U•G, all of which can form a noncanonical base pair with geometry similar to that of the canonical U•A or C•G Watson–Crick pairs. Our system is sensitive enough to measure errors at other potential mismatches that occur at frequencies as low as 1 in 500,000 codons. The ribosome appears to discriminate this efficiently against any pair with non-Watson–Crick geometry. This extreme accuracy may be necessary to allow discrimination against the errors involving near Watson–Crick pairing.     

Effect of pyritinol, a cerebral protector, on learning and memory deficits induced by prenatal undernutrition and environmental impoverishment in young rats

The study was conducted on 64 CF strain albino rats, which were equally distributed into 8 evenly matched groups following a 2 x 2 x 2 factorial design, by varying three independent factors at two levels: nutrition--normal and undernutrition; environment--enrichment and impoverishment, and drug treatment--vehicle and pyritinol (100 mg/kg, ip). Prenatal undernutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/pyritinol treatments were given during the postweaning period of the pups. The rats were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. Thereafter, the animals were tested for the passive avoidance learning. The results indicate that undernutrition caused significant original discrimination learning deficits whereas environmental deprivation attenuated both the original and reversal learning performance. Environmental impoverishment attenuated the retention of passive avoidance behaviour but undernutrition had no effect on this paradigm. Pyritinol treatment improved the learning and retention performance of normally reared rats and also attenuated the original and reversal learning deficits induced by parental undernutrition and postweaning environmental impoverishment. The results indicate that pyritinol may be useful in learning and memory deficits induced by malnutrition and environmental deprivation.