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PubMed2001

Identification of maze learning-associated genes in rat hippocampus by cDNA microarray.

Long-term memory formation requires de novo RNA and protein synthesis. To assess gene-expression changes associated with learning and memory processes, we used cDNA microarray to analyze hippocampal gene expression in male Fischer-344 rats following training in a multiunit T-maze. Here, we report the identification of 28 clones (18 known genes and 10 ESTs) for which expression increased after the maze learning. Some of the known genes appear to be involved in Ca2+ signaling, Ras activation, kinase cascades, and extracellular matrix (ECM) function, which may regulate neural transmission, synaptic plasticity, and neurogenesis. The gene-expression profile presented here provides the groundwork for future, more focused research to elucidate the contribution of these genes in learning and memory processes.

Animals↗
PubMed2004

Extending the role of associative learning processes in nicotine addiction.

Compulsive smoking is a worldwide public health problem. Although research has confirmed the importance of associative learning processes in nicotine addiction, therapies targeting nicotine-associated cues still have a high relapse rate. Most theories conceptualize nicotine as an 'outcome' that reinforces behaviors and/or changes the affective value of stimuli. Albeit important, this view does not capture the complexity of associative processes involved in nicotine addiction. For example, nicotine serves as a conditional stimulus acquiring new appetitive/affective properties when paired with a non-drug reward. Also, nicotine functions as an occasion setter that participates in higher-order associative processes that likely permit a more pervasive influence of conditioned cues that are resistant to typically cue-exposure therapy techniques. Finally, nicotine appears to amplify the salience of other stimuli that have some incentive value resulting in enhanced nicotine self-administration and conditioned reinforcement processes. Future smoking intervention strategies should take into consideration these additional associative learning processes.

Affect↗
PubMed2006

Subject-performed tasks improve associative learning in amnestic mild cognitive impairment.

Subject-performed tasks (SPTs) may facilitate the deficit in associative learning among individuals with amnestic mild cognitive impairment (aMCI) by inducing episodic integration of object-action associations. To test this hypothesis, we examined free recall and recognition memory following enactment and verbal encoding in healthy elderly controls and individuals with aMCI. Study lists contained either semantically integrated ("Bounce the ball") or crossed object-action commands, in which episodic and semantic associations were placed in opposition ("Pet the compass"). Associative learning was indeed better after SPT than verbal encoding and with integrated relative to crossed lists for the aMCI group, as it was for controls. Moreover, the degree to which SPTs reduced the semantic interference inherent in the crossed conditions was equivalent for the two groups. The results showed that enactment facilitates formation of episodic associations, even when not supported by preexisting semantic knowledge, and even among individuals who have particular difficulty forming new associations.

Adult↗
PubMed2005

Protein synthesis required for long-term memory is induced by PKC activation on days before associative learning.

Protein synthesis has long been known to be required for associative learning to consolidate into long-term memory. Here we demonstrate that PKC isozyme activation on days before training can induce the synthesis of proteins necessary and sufficient for subsequent long-term memory consolidation. Bryostatin (Bryo), a macrolide lactone with efficacy in subnanomolar concentrations and a potential therapeutic for Alzheimer's disease, is a potent activator of PKC, some of whose isozymes undergo prolonged activation after associative learning. Under normal conditions, two training events with paired visual and vestibular stimuli cause short-term memory of the mollusc Hermissenda that lasts approximately 7 min. However, after 4-h exposures to Bryo (0.25 ng/ml) on two preceding days, the same two training events produced long-term conditioning that lasted >1 week and that was not blocked by anisomycin (1 mug/ml). Anisomycin, however, eliminated long-term memory lasting at least 1 week after nine training events. Both the nine training events alone and two Bryo exposures plus two training event regimens caused comparably increased levels of the PKC alpha-isozyme substrate calexcitin in identified type B neurons and enhanced PKC activity in the membrane fractions. Furthermore, Bryo increased overall protein synthesis in cultured mammalian neurons by up to 60% for >3 days. The specific PKC antagonist Ro-32-0432 blocked much of this Bryo-induced protein synthesis as well as the Bryo-induced enhancement of the behavioral conditioning. Thus, Bryo-induced PKC activation produces those proteins necessary and sufficient for long-term memory on days in advance of the training events themselves.

Animals↗
PubMed1998

Paired-associate learning is unaffected by combined hippocampal and parahippocampal lesions in homing pigeons.

To examine whether the avian hippocampus-parahippocampus (HF) is necessary for nonspatial, paired-associate learning, as has been suggested for rodents, HF-lesioned and control homing pigeons were tested on a visual paired-associate learning task. Both groups learned equally well to discriminate trials that consisted of a stimulus preceded by its paired associate from trials that consisted of a stimulus preceded by stimuli from other paired associates (mispair trials), even when a mispair was experienced for the first time. The groups also learned equally well not to respond to 2 stimuli that were never rewarded. The results demonstrate that HF lesions do not impair nonspatial paired-associate learning in birds, suggesting that the role of HF in nonspatial cognition differs between birds and mammals.

Analysis of Variance↗
PubMed1996

Associative learning in patients with cerebellar ataxia.

It has been claimed that patients with cerebellar pathology are impaired at associative learning. Patients with cerebellar ataxia (n = 7) were taught a visual-motor associative task. The task was chosen so as to allow comparisons with data currently being collected on the effects of cerebellar lesions on associative learning in monkeys. As a group the patients were as impaired at learning the task as a group of 8 patients with Huntington's disease. When each patient was individually matched with a control of the same age and IQ, some patients with cerebellar ataxia were found to be clearly impaired, but 2 were not. Of the 4 patients who were most clearly impaired, 2 had brainstem pathology and 2 did not. The relevance of these findings is discussed in relation to views concerning the functions of the cerebellum.

Adult↗
PubMed1986

Factor analysis of the Wechsler Memory Scale: is the associate learning subtest an unclear measure?

A factor analysis of the Wechsler Memory Scale (WMS) with 30-minute delayed recall scores (percent retained) for the Logical Memory, Visual Reproduction, and Associate Learning subtests indicated that this variant of the WMS taps different types of learning and memory for new material. With regard to the verbal learning/recall subtests, Logical Memory appears to be related to attention/ concentration ability, while Associate Learning is relatively independent. The results also showed that both the easy and hard items from Associate Learning tap the same ability, providing evidence that this subtest is a measure of rote verbal learning. These results support the clinical utility of the WMS with delayed recalls in neuropsychiatric populations.

Journal Article↗
PubMed1999

Differences in neurophysiological indices of associative learning in alcohol-preferring and nonpreferring rats.

Alcohol-preferring (P) and -nonpreferring (NP) rats differ in baseline neurophysiological measures as well as in their neurophysiological responses to ethanol. In the present study, these lines of rats were assessed to determine whether they also differ in their neurophysiological responses during an associative learning paradigm. Male P and NP rats were implanted with electrodes in the frontal cortex, parietal cortex, and amygdala. Both groups were then exposed to an associative learning paradigm. During the first five sessions (conditioning phase), an infrequently presented tone was paired with the delivery of a food pellet. A second tone was also presented during these sessions, but this tone was never paired with food pellet presentation. During the second five sessions (extinction phase), neither of the tones were paired with food pellet presentation. Event-related potentials (ERPs) in response to the tones were recorded during both phases of the experiment. During the first session, the latency of the N1 and P3 waves from the cortical lead in response to the food-paired tone was significantly longer in the NP rats than in P rats. In addition, P rats displayed significant increases in the latency of the P2 wave component in the cortex and the P3A wave component in the amygdala in response to changes in the association between food pellet and tone presentation. These data indicate that the P rats were more responsive to changes in the association between food pellet delivery and tone presentation. They also suggest more enhanced associative learning in P rats than in NP rats. This enhanced learning could be an innate trait of P rats or the result of altered learning due to differences in anxiety between P and NP rats.

Acoustic Stimulation↗
PubMed2006

Dissociating the effects of automatic activation and explicit expectancy on reaction times in a simple associative learning task.

After repeated associations between two events, E1 and E2, responses to E2 can be facilitated either because participants consciously expect E2 to occur after E1 or because E1 automatically activates the response to E2, or because of both. In this article, the authors report on 4 experiments designed to pit the influence of these 2 factors against each other. The authors found that the fastest responses to a target in a reaction time paradigm occurred when automatic activation was highest and conscious expectancy lowest. These results, when considered together with previous findings indicating that, under most conditions, the relation between expectancy and reaction times is in the opposite direction, are indicative of a reversed association-an interaction pattern that J. C. Dunn and K. Kirsner (1988) demonstrated to be the only one that unambiguously points to the involvement of independent processes.

Adolescent↗
PubMedDate not supplied

Arousal and paired-associate learning. Evidence refuting the action decrement theory of Walker and Tarte (1963).

Walker and Tarte (1963) postulate that at short retention intervals high arousal paired-associates are reproduced more poorly than low arousal items. Walker and colleagues believe that this hypothesis is confirmed by their paired-associate learning studies. However, results of these paired-associate learning studies are position confounded artifacts. Better recall of low arousal items at short-term retention is caused by the coincidence of the recency effect and low arousal at the end of the trial. When these position effects are controlled there is no action decrement for the high arousal paired-associates. To test this assumption, the Kleinsmith and Kaplan study (1963) was replicated and two other variations were conducted. In these three studies with 76 subjects, which were tested at two minutes or 1 week, the action decrement occurs only when the two position effects coincide.

Adult↗
PubMed2005

Retrospective revaluation as simple associative learning.

Backward blocking, unovershadowing, and backward conditioned inhibition are examples of retrospective revaluation phenomena that have been suggested to involve more than simple associative learning. Models of these phenomena have thus used additional concepts, for example, appealing to attentional effects or more elaborate learning mechanisms. The author shows that a suitable representation of stimuli, paired with a careful analysis of the discriminations faced by animals, leads to an account of these and other phenomena in terms of a simple elemental model of associative learning, with essentially the same learning mechanism as the R. A. Rescorla and A. R. Wagner (1972) model. The author concludes with a discussion of some implications for theories of learning.

Animals↗
PubMed1986

Paired associate learning: normative data for differences between high and low associate word pairs.

Wilson, Bacon, Kaszniak, and Fox (1982) suggest that the learning of low associate pairs on the Wechsler Memory Scale involves episodic memory alone while the learning of high associate pairs involves semantic memory as well. Tulving (1983) also comments that, whereas some information in episodic memory is relatively unorganized and access to its content tends to be deliberate and requiring conscious effort (e.g., low associate pairs), information in semantic memory is organized and access to its content is more automatic (e.g., high associate pairs). As there may be occasions when it would be useful to compare these two types of memory functioning, differential diagnosis between depressive pseudodementia and organic dementia for example, normative data is provided enabling the calculation of the frequency with which differences between the learning of the two kinds of associate occur, based on the performance of 500 subjects with no known neuropsychiatric involvement.

Adult↗
PubMed2000

Associative learning is enhanced by selective neuronal nitric oxide synthase inhibitors and retarded by a nitric oxide donor in the rabbit.

RATIONALE: Previous studies had reported that the nitric oxide (NO) donor, sodium nitroprusside (SNP), retarded and the non-specific NO synthase (NOS) inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), enhanced acquisition of classically conditioned responses (CRs). These effects of IV SNP and IP L-NAME on CR acquisition occurred in the absence of any effect on non-associative processes or performance variables and at a time when there were no alterations in blood pressure or heart rate. OBJECTIVES: In this study, we examined whether the changes in associative learning produced by L-NAME and SNP were due to their central effects on NO content of brain. To this end, we examined the effects of the selective neuronal NOS inhibitors 7-nitroindazole (7-NI) and AR-R 17477 and the effects of central (ICV) administration of the NO donor SNP on learning. METHODS: Effects of drugs on CR acquisition were determined during classical conditioning of the rabbit's nictitating membrane (NM) response. Explicitly unpaired presentations of conditioned stimuli (CSs) and unconditioned stimuli (USs) were employed to measure non-associative levels of responding and unconditioned response (UR) topography. RESULTS: The SC injection of 7-NI and AR-R 17477 significantly enhanced associative learning while ICV administration of SNP significantly retarded learning. CONCLUSION: Production of NO within the brain by neuronal NOS normally acts to retard associative learning presumably by decreasing excitability within neuronal circuits involved in the acquisition of the classically conditioned NM reflex.

Amidines↗
PubMed1998

Conditional associative learning and the hippocampal system.

Rats with lesions of the fornix, the dorsal hippocampus, or a control operation were trained on a spatial-visual conditional associative learning task in which they had to learn to associate particular locations with specific visual stimuli. Animals with damage of the fornix were able to learn the task at a rate comparable to that of the control animals, but the performance of the hippocampal rats was significantly impaired in comparison with that of both the control and the fornix groups. In a second experiment, lesions to the fornix or the dorsal hippocampus significantly impaired performance on a spatial working memory task, the eight-arm radial maze. These findings suggest that the interaction between the hippocampus and subcortical structures via the fornix may be critical only for certain types of spatial learning and memory.

Animals↗
PubMed1998

Acute inactivation of the inferior olive blocks associative learning.

Can acute inactivation of the inferior olive block associative learning? We anaesthetized the inferior olive with lidocaine while rabbits simultaneously: (i) performed conditioned nictitating membrane responses to a flashing light to which they had already been trained; and (ii) underwent their first experience with classical conditioning of the same response to a tone. Inactivation of the inferior olive immediately and reversibly abolished the performance of conditioned responses and prevented learning during rabbits' initial conditioning with a tone-conditioned stimulus. When olivary function was restored, rabbits showed no signs of having learned under olivary anaesthesia. The experiment demonstrates that an acute disruption in olivary function can block learning, in addition to severely degrading motor control. The results are interpreted to indicate the importance of the inferior olive in optimizing learning, perhaps through a general role in regulating temporal processing.

Anesthetics, Local↗
PubMed2005

Cortico-hippocampal interaction and adaptive stimulus representation: a neurocomputational theory of associative learning and memory.

Computational models of the hippocampal region link psychological theories of associative learning with their underlying physiological and anatomical substrates. Our approach to theory development began with a broad description of the computations that depend on the hippocampal region in classical conditioning (Gluck and Myers, 1993 and Gluck and Myers, 2001). In this initial model, the hippocampal region was treated as an Information-processing system that transformed stimulus representations, compressing (making more similar) representations of inputs that co-occur or are otherwise redundant, while differentiating (or making less similar) representations of inputs that predict different future events. This model led to novel predictions for the behavioral consequences of hippocampal-region lesions in rodents and of brain damage in humans who have amnesia or are in the earliest stages of Alzheimer's disease. Many of these predictions have, since been confirmed by our lab and others. Functional brain imaging studies have provided further supporting evidence. In more recent computational modeling, we have shown how some aspects of this proposed information-processing function could emerge from known anatomical and physiological characteristics of the hippocampal region, including the entorhinal cortex and the septo-hippocampal cholinergic system. The modeling to date lays the groundwork for future directions that increase the depth of detail of the biological modeling, as well as the breadth of behavioral phenomena addressed. In particular, we are working now to reconcile these kinds of incremental associative learning models with other models of the hippocampal region that account for the rapid formation of declarative memories.

Animals↗