Acquisition of a simple spatial discrimination as a function of the amount of reinforcement.
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Learning↗
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Drive specificity and learning: the acquisition of a spatial response to food under conditions of water deprivation and food satiation.
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Drive↗
An experimental test of the selective principle of association of drive stimuli.
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Conditioning, Psychological↗
Generalization of secondary reinforcement.
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Humans↗
The effects of AMPA-induced lesions of the medial septum and vertical limb nucleus of the diagonal band of Broca on spatial delayed non-matching to sample and spatial learning in the water maze.
These experiments investigated in the rat the impact on spatial delayed non-matching to sample and on acquisition of the Morris water maze of (i) AMPA-induced lesions of the medial septal nucleus, which produced a marked reduction of hippocampal choline acetyltransferase activity and acetylcholine levels (measured using in vivo dialysis) together with lesser reductions in cholinergic markers in the cingulate cortex and (ii) similar AMPA-induced lesions of the vertical limb nucleus of the diagonal band of Broca (vDB), which produced more marked reductions in cholinergic markers in the cingulate cortex than in the hippocampus. Medial septal lesions produced a delay-dependent deficit in spatial working memory, while lesions of the vDB resulted in a delay-independent performance deficit. In addition, rats with vDB lesions adopted biased response strategies during the imposition of long delays. Neither lesion significantly affected the acquisition of a spatial reference memory task, the Morris water maze. The results are discussed in terms of cholinergic- and GABAergic-dependent functions of the hippocampal formation and cingulate cortex in spatial short-term and reference memory.
Acetylcholine↗
The effects of prenatal cocaine exposure on subsequent learning in the rat.
This chapter has reviewed the animal studies related to prenatal cocaine administration and subsequent learning. A summary of these studies and their findings is given in table 1. It is important to note that there is a relative scarcity of reports in this area. Given the potential number of infants that might be exposed to cocaine prenatally, it is certain that more work needs to be done. Second, from this table and the preceding review, it is difficult to conclude that prenatal cocaine exposure has wide-ranging effects. There certainly appears to be ample evidence from Spear's lab that prenatal cocaine exposure disrupts early olfactory learning. These findings are in need of independent replication. In fact, the authors have partially replicated a deficit in an odor-aversion task following gestational cocaine administration. The evidence provided by Spear and colleagues (1989a, 1989b), however, indicates that this deficit is relatively transitory and is not found in animals after perhaps 15 days of Furthermore, it does not appear that these cocaine-exposed animals are incapable of learning. In the Goodwin and colleagues (1992) study, where animals were given either 2, 3, or 4 acquisition trials, animals exposed to cocaine prenatally and reared by surrogate untreated mothers did learn the association when given 4 trials. It must be stressed, however, that early deficits that diminish as the animals mature or deficits which can be overcome by repetition can still have long-lasting consequences. Requiring more experience with an association prior to learning that association or having a transitory learning deficit in no way diminishes its potential importance for the organism. On more common tasks of learning, such as passive and shuttle avoidance and maze learning, there is really very little evidence to support the notion that cocaine is acting as a behavioral teratogen. The available evidence would appear to indicate that significant, biologically meaningful deficits on these tasks are not found over a wide range of doses. There are a number of reasons for these failures to find effects. It may be that these tasks are too simple to detect underlying behavioral anomalies. Passive avoidance is a simple task that is easily learned by animals by the time of weaning. Active avoidance is much more difficult, but it too may not place enough challenges on the organism. The work by Heyser and colleagues (1992b) may signal that more complicated tasks, such as reversal of a conditional discrimination, might be necessary to show cocaine's behavioral teratogenic action. However, even in this case the effect was not very substantial, consisting of less than one extra incorrect response relative to controls prior to the first reward. More challenging situations such as successive discriminations (e.g., learning to learn) might lead to bigger differences in performance between cocaine-exposed animals and controls. These types of tasks need to be assessed. Similarly, perhaps cocaine-exposed animals need to be challenged physiologically, either by placing them in extremely stressful situations or assessing their response to other drugs that disrupt normal physiological functioning (see Spear, this volume). Another reason for a failure to find substantial effects on a wide range of behavioral assessments is that cocaine may act as a behavioral teratogen through a number of different mechanisms. It might be a direct toxin to certain developing neurotransmitter systems, it may function indirectly by inducing hypoxia, or both. If the mechanism of action varies in different animals and the effects are not large in any animal, then it would be extremely difficult to detect group differences using the sample sizes normally assessed in these studies. It may be that only a small subset of a group of animals is affected and that group variability must be assessed in addition to alterations in group means. Finally, it may be that cocaine is not a behavi
Animals↗
Effects of US devaluation on win-stay and win-shift radial maze performance in rats.
Previous studies have shown double dissociations between win-stay and win-shift radial maze learning in terms of their underlying neural substrates. To examine the content of the associations formed in the two tasks, the authors devalued the food unconditioned stimulus (US) by taste aversion to differentiate stimulus-stimulus(CS-US) and stimulus-response (CS-CR) learning. US devaluation was performed in rats that were over- or undertrained on the win-stay task. Devaluation substantially reduced food consumption on the maze but failed to disrupt choice accuracy, regardless of the amount of training. Devaluation did not affect latency in overtrained rats but did increase latency in undertrained rats. In the win-shift task, devaluation caused rats to reject the reinforcer, yet they continued to accurately win-shift, but with significantly longer latencies (Experiment 3). The results suggest that an S-R association may mediate performance after extended win-stay training. In contrast, a US representation appears to be recalled during early win-stay and win-shift performance.
Animals↗
sgk, a primary glucocorticoid-induced gene, facilitates memory consolidation of spatial learning in rats.
By using differential display PCR, we have identified 98 cDNA fragments from the rat dorsal hippocampus that are expressed differentially between the fast learners and slow learners in the water maze learning task. One of these cDNA fragments encodes the rat serum- and glucocorticoid-inducible kinase (sgk) gene. Northern blot analysis revealed that the sgk mRNA level was approximately 4-fold higher in the hippocampus of fast learners than slow learners. In situ hybridization results indicated that sgk mRNA level was increased markedly in CA1, CA3, and dentate gyrus of hippocampus in fast learners. Transient transfection of the sgk mutant DNA to the CA1 area impaired, whereas transfection of the sgk wild-type DNA facilitated water maze performance in rats. These results provide direct evidence that enhanced sgk expression facilitates memory consolidation of spatial learning in rats. These results also elucidate the molecular mechanism of glucocorticoid-induced memory facilitation in mammals.
Animals↗
Pfiesteria toxin and learning performance.
Pfiesteria piscicida is an estuarine dinoflagellate involved with fish kills along the east coast of the United States. We previously documented a radial-arm maze learning deficit in rats exposed to Pfiesteria that may be related to cognitive deficits seen in humans after accidental Pfiesteria exposure. The current study elucidated important behavioral parameters of this deficit. There were six dose groups. Forty (10/group) adult female Sprague-Dawley rats were injected (s.c.) with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600, 106,800, or 320,400 Pfiesteria cells/kg of rat body weight or a cell-free filtrate of the 106,800 cells/kg dose). One control group (N = 10) was injected with saline and one (N = 10) with aquarium water not containing Pfiesteria. Half of the rats in each group were tested on an 8-arm radial maze in a standard test room, and the other half were tested on the radial maze in a sound-attenuating chamber. In the standard maze room, there was a significant effect of Pfiesteria (p < 0.05) impairing choice accuracy improvement over the first six sessions of training among rats administered 106,800, 320,400, and the 106,800 cells/kg filtered sample. In contrast, there was no indication of an effect of Pfiesteria when the rats were tested on the same configuration radial maze in the sound-attenuating chamber. After 18 sessions of training in one room, the rats were switched for six sessions of testing in the other room and finally were switched back to their original room for three sessions. There was a significant Pfiesteria-induced deficit when the rats were tested in the standard test room but not when they were tested in the sound-attenuating chamber. When the Pfiesteria-exposed rats were initially switched from the sound-attenuating chamber to the standard test room they performed significantly worse than controls, whereas Pfiesteria-treated rats switched from the standard test room to the sound-attenuating chamber did not perform differently from controls. These results suggest that the Pfiesteria-induced learning impairment may result from the negative impact of distracting stimuli. At the time of the learning impairment, no overt Pfiesteria-related effects were seen using a functional observational battery and no overall response latency effects were seen, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the initial use of the figure-8 maze in this line of research, the rats in the same Pfiesteria treatment groups that showed significant deficits in the radial-arm maze showed greater declines in activity rates in a 1-h figure-8 locomotor activity test. Both the 106,800 and 320,400 Pfiesteria cells/kg groups showed significantly greater linear trends of activity decline relative to tank water-treated controls. This reflected an initial slight hyperactivity in the Pfiesteria-treated animals followed by a decrease to control levels. Pfiesteria effects in the figure-8 maze and in early radial-arm maze training may be useful in a rapid screen for identifying the critical toxin(s) of Pfiesteria in future studies.
Animals↗
Reinforcement learning in random neural networks for cascaded decisions.
The Random Neural Network (RNN) model, in which signals travel as voltage spikes rather than as fixed signal levels, represents more closely the manner in which signals are transmitted in biophysical neural networks. In this paper a reinforcement learning strategy is proposed to make a sequence of cascaded decisions to achieve a goal while aiming to optimize the total cost of the cascaded decisions. For this purpose, RANs are used to model the system and a weight update rule together with a reinforcement function is provided. The performance of the learning strategy is analysed by applying it to the maze learning problem. The simulation results show that the performance of the system is highly dependent on the chosen reinforcement function and quite satisfactory results are obtained when the reinforcement function takes the recency effect into consideration.
Action Potentials↗
Exposure to music in the perinatal period enhances learning performance and alters BDNF/TrkB signaling in mice as adults.
Music has been suggested to have a beneficial effect on various types of performance in humans. However, the physiological and molecular mechanism of this effect remains unclear. We examined the effect of music exposure during the perinatal period on learning behavior in adult mice, and measured the levels of brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), which play critical roles in synaptic plasticity. In addition, we measured the levels of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and mitogen-activated protein kinase (MAPK), downstream targets of two main pathways in BDNF/TrkB signaling. Music-exposed mice completed a maze learning task with fewer errors than the white noise-exposed mice and had lower levels of BDNF and higher levels of TrkB and PDK1 in the cortex. MAPK levels were unchanged. Furthermore, TrkB and PDK1 protein levels in the cortex showed a significant negative correlation with the number of errors on the maze. These results suggest that perinatal exposure of mice to music has an influence on BDNF/TrkB signaling and its intracellular signaling pathway targets, including PDK1, and thus may induce improved learning and memory functions.
3-Phosphoinositide-Dependent Protein Kinases↗
Spatial learning and long-term potentiation of mutant mice lacking D-amino-acid oxidase.
We evaluated the role of D-amino-acid oxidase on spatial learning and long-term potentiation (LTP) in the hippocampus, since this enzyme metabolizes D-amino-acids, some of which enhance the N-methyl-D-aspartate receptor functions. The Morris water maze learning and the LTP in the CA1 area of the hippocampal slice were observed in wild-type mice and mutant mice lacking D-amino-acid oxidase. The mutant mice showed significantly shorter platform search times in the water maze and significantly larger hippocampal LTPs than the wild-type mice. These results suggest that the abundant D-amino-acids in the mutant mouse brain facilitate hippocampal LTP and spatial learning.
6-Cyano-7-nitroquinoxaline-2,3-dione↗
Permanent bilateral common carotid arterial ligation impairs visual but not auditory conditioned avoidance behavior in rats.
The effect of permanent bilateral common carotid arteries ligation (BCCAL) on visual function was investigated using conditioned avoidance task in Wistar rats. Behavioral experiments began 1 month after ligation. When light was used as a conditioned stimulus, the number of avoidance failures of BCCAL rats was higher than that of sham-operated control animals. However, the performance of the same avoidance task using a buzzer instead of light stimulus was not impaired by BCCAL. BCCAL impaired performance in the Morris water maze learning task and the rhythm of diurnal and nocturnal spontaneous motor activities. These results indicate that BCCAL treatment induces dysfunction of the visual system in rats, and consequently results in apparent deficits in conditioned avoidance behavior. BCCAL-induced deficits in performance in the water maze and rhythm of the motor activities are at least partially attributable to optical dysfunction.
Acoustic Stimulation↗
A relation between maze performance and increased ethanol intake in Long-Evans rats.
In addition to the neurochemical and genetic basis of high ethanol consumption, there has been renewed interest in studying the role of behavioral variables and their relation to ethanol consumption. The present study was designed to assess whether a relation exists between a behavioral variable such as maze learning ability and ethanol consumption. Sixty, male, Long-Evans rats, exposed to food and water ad libitum, were given a daily trial in a complex, 16-arm T-maze for 19 consecutive days. The number of errors and time to complete the maze were monitored. Individual maze variable scores were transformed and then combined to allot each animal with an index of overall maze performance, with a smaller maze index score denoting good performance. After completion of maze testing, animals were given alternate-day, free-choice presentations of water and ascending doses of ethanol solutions (2%-10%), followed by a 10-day maintenance period with 10% ethanol. Animals were subsequently separated into two groups of high and low drinkers to examine any relation between differential ethanol intake and maze performance. A significant negative correlation between maze index and ethanol intake for the high drinkers group indicated that a smaller maze index was related to increased ethanol intake. No significant correlation was obtained for the low drinkers group. These results seem to indicate that individual variation in learning ability seems to be related to increased ethanol intake. Thus, innate learning processes may be a relevant trait when one attempts to understand the behaviors related to ethanol intake and preference.
Alcohol Drinking↗
Pentyl-4-yn-valproic acid enhances both spatial and avoidance learning, and attenuates age-related NCAM-mediated neuroplastic decline within the rat medial temporal lobe.
2-N-Pentyl-4-pentynoic acid [pentyl-4-yn-valproic acid (VPA)] is an analogue of valproic acid that induces neuritogenesis and increases neural cell adhesion molecule (NCAM) prevalence in cultured neural cells. As memory consolidation involves synapse growth, aided by cell adhesion molecule function, we determined whether or not pentyl-4-yn-VPA had cognition-enhancing properties. Pentyl-4-yn-VPA (16-85 mg/kg) significantly improved water maze learning and task retention when given prior to each training session. Acute administration of pentyl-4-yn-VPA also influenced memory consolidation processes as, when given at 3 h post-passive avoidance training, the amnesia induced by scopolamine given 6 h post-training was prevented in a dose-dependent manner. Chronic administration of pentyl-4-yn-VPA (16.8 or 50.4 mg/kg) also significantly reduced escape latencies in the water maze task, 24 h following the last drug administration. This improved spatial learning was accompanied by enhanced neuroplasticity as the expression of NCAM polysialylated neurons in the infragranular zone of the dentate gyrus and in layer II of the perirhinal and piriform cortex was increased significantly following chronic drug treatment. The cognition-enhancing qualities of pentyl-4-yn-VPA, combined with its ability to attenuate the age-related loss of the NCAM polysialylation state, suggest that it may effectively slow the onset of cognitive decline.
Aging↗
Cerebellar contributions to instrumental learning.
There is emerging evidence that the cerebellum is involved in spatial and nonspatial instrumental learning tasks. Cerebellar-lesioned animals have deficits in water maze learning tasks that may be explained by two-way interactions with higher order brain regions. There is suggestive evidence that cerebellar modulation extends to shock avoidance and discrimination learning. Although this evidence needs to be confirmed by a wider range of lesion methods and choice of learning tasks, it is in line with the hypothesis that the cerebellum affects cognitive processes and is not strictly concerned with motor control and the acquisition and retention of conditioned reflexes.
Animals↗
Reduced spatial learning in mice infected with the nematode, Heligmosomoides polygyrus.
Parasite modification of host behaviour influences a number of critical responses, but little is known about the effects on host spatial abilities. This study examined the effects of infection with the intestinal trichostrongylid nematode, Heligmosomoides polygyrus, on spatial water maze learning by male laboratory mice, Mus musculus. In this task individual mice had to learn the spatial location of a submerged hidden platform using extramaze visual cues. Determinations of spatial performance were made on day 19 post-infection with mice that had been administered either 50 or 200 infective larvae of H. polygyrus. The infected mice displayed over 1 day of testing (6 blocks of 4 trials) significantly poorer acquisition and retention of the water maze task than either sham-infected or control mice, with mice that had received 200 infective larvae displaying significantly poorer spatial performance than individuals receiving 50 larvae. The decrease in spatial learning occurred in the absence of either any symptoms of illness and malaise, or any evident motor, visual and motivational impairments. It is suggested that in this single host system the parasitic infection-induced decrease in spatial learning arises as a side-effect of the host's immunological and neuromodulatory responses and represents a fitness cost of response to infection.
Analysis of Variance↗
Effects of d-amphetamine and d-fenfluramine on performance of rats in a food maze.
d-Amphetamine and d-fenfluramine caused different patterns of disruption in a learned maze performance reinforced with food. A 0.8 mg/kg dose of amphetamine increased correct and incorrect (errors) alley entrances as well as earned reinforcers consumed. Larger doses (1.6-3.2 mg/kg) decreased correct responses, increased errors, and resulted in earned reinforcers not being consumed. Metergoline pretreatment did not reverse these deficits. d-Fenfluramine (1.5 and 3.0 mg/kg) reduced correct responses dose- relatedly with a slight increase in errors after the larger dose; all earned reinforcers were consumed. Pretreatment with metergoline reversed the deficit in correct responses but not the errors. Combinations of d-amphetamine and d-fenfluramine produced greater deficits than each drug separately, with fewer correct responses and an increase in reinforcers earned but not consumed. Metergoline pretreatment before the combination did not reverse these effects but increased alley entrances scored as errors. The results indicate that the d-fenfluramine but not the d-amphetamine deficit relates to a 5-hydroxytryptamine (5-HT) mechanism. Furthermore, the enhanced effect of the combination appears to relate to drug interactions not dependent upon a 5-HT component.
Animals↗