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Molecular, cellular, and neuroanatomical substrates of place learning.

Learning and remembering the location of food resources, predators, escape routes, and immediate kin is perhaps the most essential form of higher cognitive processing in mammals. Two of the most frequently studied forms of place learning are spatial learning and contextual conditioning. Spatial learning refers to an animal's capacity to learn the location of a reward, such as the escape platform in a water maze, while contextual conditioning taps into an animal's ability to associate specific places with aversive stimuli, such as an electric shock. Recently, transgenic and gene targeting techniques have been introduced to the study of place learning. In contrast with the abundant literature on the neuroanatomical substrates of place learning in rats, very little has been done in mice. Thus, in the first part of this article, we will review our studies on the involvement of the hippocampus in both spatial learning and contextual conditioning. Having demonstrated the importance of the hippocampus to place learning, we will then focus attention on the molecular and cellular substrates of place learning. We will show that just as in rats, mouse hippocampal pyramidal cells can show place specific firing. Then, we will review our evidence that hippocampal-dependent place learning involves a number of interacting physiological mechanisms with distinct functions. We will show that in addition to long-term potentiation, the hippocampus uses a number of other mechanisms, such as short-term-plasticity and changes in spiking, to process, store, and recall information. Much of the focus of this article is on genetic studies of learning and memory (L&M). However, there is no single experiment that can unambiguously connect any cellular or molecular mechanism with L&M. Instead, several different types of studies are required to determine whether any one mechanism is involved in L&M, including (i) the development of biologically based learning models that explain the involvement of a given mechanism in L&M, (ii) lesion experiments (genetics and pharmacology), (iii) direct observations during learning, and (iv) experiments where learning is triggered by turning on the candidate mechanism. We will show how genetic techniques will be key to unraveling the molecular and cellular basis of place learning.

Animals↗
PubMed1981

The dichotomy between classical conditioned and cognitively learned anxiety.

This paper describes how fears develop on the basis of one or other of two distinct processes--direct autonomic conditioning or the establishment of new cognitive associations to already existing fears. The dichotomy relates both to the appropriate fears of everyday life and to neurotic fears. In the case of the latter, the appropriate treatment procedure should be dictated by the fear basis that behavior analysis reveals. Failure to carry out such analysis is the reason for much confusion and inconclusiveness in therapeutic outcome studies. A retrospective survey of anxiety cases revealed that one-third of their fears were cognitively based and two-thirds due to autonomic conditioning. A study of a clinical population on the basis of a questionnaire designed to separate between cognitively based and conditioned fears has shown the expected bi-modal distribution. These findings undercut the conditioning versus cognition controversy on the causation of neurotic fears.

Adolescent↗
PubMed2002

Expectancy-learning and evaluative learning in human classical conditioning: affective priming as an indirect and unobtrusive measure of conditioned stimulus valence.

It has been argued that in classical conditioning two processes might be operative. First, one may learn that the conditioned stimulus (CS+) is a valid predictor for the occurrence of the biologically negative or positive event (US; expectancy-learning). Second, one may learn to perceive the conditioned stimulus itself as a negative or positive stimulus, depending on the valence of the event it has been associated with (evaluative learning). Until the present, however, both forms of learning have been investigated using rather different conditioning procedures. Using a differential aversive conditioning preparation with pictures of human faces as CSs and an electrocutaneous stimulus as US, we were able to demonstrate that both forms of learning can co-occur. Moreover, the extent of evaluative learning in this aversive conditioning procedure did not significantly differ from the amount of evaluative learning in an evaluative conditioning procedure with positive and negative adjectives as USs, which was administered to the same participants. In the present study evaluative learning was not only indexed by direct evaluative ratings, but we introduced affective priming as an indirect and unobtrusive, reaction time based measure of stimulus valence. Finally, imagery instructions during acquisition did not facilitate expectancy-learning nor evaluative learning.

Adult↗
PubMed1990

Grouping students for instruction: effects of learning style on achievement and attitudes.

The present study examined the effects of matching and mismatching American middle-school students with a preference for learning alone or learning with peers with selected instructional treatments in order to determine the impact upon their attitudes and achievement in social studies. Analysis revealed that the learning-alone preference performed significantly better in the learning-alone condition and that the learning-with-peers preference performed significantly better in the learning-with-peers condition. However, no-preference students also performed significantly better in the learning-alone condition than with peers. In addition, data revealed that the learning-alone and the learning-with-peers students had significantly more positive attitudes when matched with their preferred learning style; the nopreference students had more positive attitudes in the learning-alone condition.

Achievement↗
PubMed2001

High levels of estradiol disrupt conditioned place preference learning, stimulus response learning and reference memory but have limited effects on working memory.

The present study investigated the effects of high levels of estradiol in female rats on four different radial arm maze tasks: the hippocampus-dependent spatial working-reference memory task; the prefrontal cortex-hippocampus dependent delayed win-shift task; the striatum-dependent cued win-stay task; and the amygdala-dependent conditioned place preference task. Ovariectomized female rats were injected daily with either 10 microg of estradiol benzoate or sesame oil vehicle approximately 4 h prior to testing. In Experiment 1, treatment with estradiol disrupted learning on the spatial working-reference memory task by increasing the number of reference memory errors to reach criterion. In Experiment 2, treatment with estradiol had no significant effect on the delayed win-shift task. In Experiment 3, treatment with estradiol resulted in impaired performance on a striatum-dependent cued win-stay task. In Experiment 4, treatment with estradiol impaired the acquisition of a conditioned place-preference task. Taken together these findings suggest that high levels of estradiol inhibit reference memory, stimulus response learning, and amygdala-dependent appetitive conditioning while having little effect on working memory.

Amygdala↗
PubMed2003

Associative learning and memory in Drosophila: beyond olfactory conditioning.

The associative learning abilities of the fruit fly, Drosophila melanogaster, have been demonstrated in both classical and operant conditioning paradigms. Efforts to identify the neural pathways and cellular mechanisms of learning have focused largely on olfactory classical conditioning. Results derived from various genetic and molecular manipulations provide considerable evidence that this form of associative learning depends critically on neural activity and cAMP signaling in brain neuropil structures called mushroom bodies. Three other behavioral learning paradigms in Drosophila serve as the main subject of this review. These are (1) visual and motor learning of flies tethered in a flight simulator, (2) a form of spatial learning that is independent of visual and olfactory cues, and (3) experience-dependent changes in male courtship behavior. The present evidence suggests that at least some of these modes of learning are independent of mushroom bodies. Applying targeted genetic manipulations to these behavioral paradigms should allow for a more comprehensive understanding of neural mechanisms responsible for diverse forms of associative learning and memory.

Journal Article↗
PubMed2006

Serotonin and dopamine in the parabrachial nucleus of rats during conditioned taste aversion learning.

A microdialysis technique was used to monitor changes in serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) and dopamine (DA) in the extracellular space of the parabrachial nucleus (PBN) of rats to estimate the contribution of these neurotransmitter systems to the acquisition of conditioned taste aversion (CTA). A significant (280%) enhancement of 5-HT was found immediately after saccharin drinking (CS). I.p. injection of unconditioned stimulus LiCl alone (after water drinking) also increased level of 5-HT (200%). However, when saccharin intake was followed by injection of LiCl (CS-US pairing), no change in 5-HT was observed. 5-HIAA and DA were unaffected by any of the above treatments. Thus in spite of elevation of 5-HT in PBN following saccharin consumption alone (CS) or LiCl administration alone (US) no changes in 5-HT occurred after pairing of both stimuli (CS-US). Our work demonstrates that participation of 5-HT in acquisition of CTA appears to be unlikely, and also DA appears not to be engaged in this acquisition at all. At the level of the PBN 5-HT participates mainly in CS and/or US stimuli processing, where this phenomenon has close relationship to other important physiological mechanisms, involved in behavioral control. Such as anxiety, alimentation intake.

Animals↗
PubMed2000

Spatial learning, contextual fear conditioning and conditioned emotional response in Fmr1 knockout mice.

Fmr1 knockout mice are an animal model for fragile X syndrome, the most common form of heritable mental retardation in humans. Fmr1 knockout mice exhibit macro-orchidism and cognitive and behavioural deficits reminiscent of the human phenotype. In the present study additional behavioural and cognitive testing was performed. Knockouts and control littermates were subjected to a spatial learning test using a plus-shaped water maze. Animals had to learn the position of a hidden escape platform during training trials. The position of this platform was changed during subsequent reversal trials. Previously reported deficits in reversal learning were replicated, but we also observed significant differences during the acquisition trials. A plus-shaped water maze experiment with daily changing platform positions failed to provide clear evidence for a working memory impairment, putatively underlying the spatial learning deficits. Two different test settings were used to examine the reported deficit of Fmr1 knockout mice in fear conditioning. Conditioned fear responses were observed in a contextual fear test, and the ability to acquire an emotional response was tested by means of response suppression in a conditioned emotional response procedure. Neither protocol revealed significant differences between controls and knockouts.

Acoustic Stimulation↗
PubMed2003

Conditioned taste aversion learning in leptin-receptor-deficient db/db mice.

The db/db mouse has defective leptin receptors. The defects lead to impairments of leptin regulation of food intake and body weight, and result in the expression of diabetic symptoms such as hyperinsulinemia, hyperglicemia, and extreme obesity. Recent studies have proposed that leptin may also affect memory and learning processes. To examine this possibility, we compared the ability of leptin-receptor-deficient db/db mice and their normal lean litter mates to form and extinguish a conditioned taste aversion (CTA) for saccharin. We used a short-term (10 s) lick test and a long-term (48 h) two bottle preference test for measurement of consumption of test solutions. On the first day after conditioning to avoid saccharin, the db/db mice showed preference scores for saccharin as low, and aversion thresholds for sucrose lower than that of the lean mice. During the extinction test trials beginning from the second up to the 30th day after conditioning, numbers of licks and preference scores for aversive saccharin and sucrose appeared to be larger, and recovered faster to the control levels in db/db mice. These results indicate that db/db mice with leptin-receptor-deficiency may show equal capacity to form CTAs for saccharin, greater generalization from saccharin to sucrose, and a faster rate of extinction. This suggests that disruption of leptin signalling does not inhibit acquisition of CTA learning, but impairs its extinction. This differential contribution of the leptin system on CTA processes may be due to differential distribution of leptin receptors in the CTA-related brain areas.

Animals↗
PubMed1988

Attenuation of neophobia and conditioned taste aversion in the rabbit.

The phenomenon of taste neophobia to apple juice does exist in the rabbit. It was found that malic acid was the main stimulus source. Attenuation of taste neophobia was due to neuronal processes which took place between rather than during drinking sessions. Conditioned taste aversion learning took place if apomorphine was injected after apple juice intake.

Animals↗