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At least 271 records · Page 15Linked to original sources
PubMed2002

Differential muscarinic and NMDA contributions to visuo-spatial paired-associate learning in rhesus monkeys.

RATIONALE: Early, accurate detection of degenerative neurological disorders such as Alzheimer's disease (AD) is essential for therapies designed to slow disease progression. Performance of a touch-screen mediated visuo-spatial paired-associates learning (vsPAL) task predicts neurocognitive decline in elderly populations presenting with mild cognitive impairment and distinguishes AD patients from elderly depressed individuals. Translation of this cognitive task to a non-human model may therefore provide an improved tool for study of the etiology and treatment of dementia. OBJECTIVE: The goal of the current study was to contrast cholinergic and glutamatergic contributions to performance of this AD-sensitive task by challenging rhesus monkeys performing vsPAL with muscarinic antagonist and non-competitive NMDA antagonist drugs. METHODS: Seven monkeys were trained to perform vsPAL and then serially challenged with acute doses of scopolamine (3, 10, 17 microg/kg, IM) and ketamine (0.3, 1.0, 1.78 mg/kg, IM). RESULTS: Scopolamine produced a dosexdifficulty related impairment of both recognition memory and incremental acquisition aspects of task performance. In contrast, ketamine administration resulted in a dose-dependent impairment of recognition memory but not incremental acquisition. CONCLUSIONS: Monkeys' performance of a task sensitive to AD in humans was impaired by two classic pharmacological models of cognitive impairment, therefore supporting the use of this nonhuman model to explore mechanisms of AD-associated cognitive decline. The differential pattern of impairment observed is consistent with a hypothesis that muscarinic mechanisms are required for linking external events with an existing internal representation, whereas NMDA mechanisms are required for the formation/strengthening of such an internal representation.

Animals↗
PubMed2004

The role of the lateral frontal cortex in causal associative learning: exploring preventative and super-learning.

Prediction error--a mismatch between expected and actual outcome--is critical to associative accounts of inferential learning. However, it has proven difficult to explore the effects of prediction error using functional magnetic resonance imaging (fMRI) while excluding the confounding effects of stimulus novelty and incorrect responses. In this event-related fMRI study we used a three-stage experiment generating preventative- and super-learning conditions. In both cases, it was possible to generate prediction error within a causal associative learning experiment while subtracting the effects of novelty and error. We show that right lateral prefrontal cortex (PFC) activation is sensitive to the magnitude of prediction error. Furthermore, super-learning activation in this region of PFC correlates, across subjects, with the amount learned. We thus provide direct evidence for a brain correlate of the surprise-dependent mechanisms proposed by associative accounts of causal learning. We show that activity in right lateral PFC is sensitive to the magnitude, though not the direction, of the prediction error. Furthermore, its activity is not directly explicable in terms of novelty or response errors and appears directly related to the learning that arises out of prediction error.

Adult↗
PubMed2006

Dopamine, prediction error and associative learning: a model-based account.

The notion of prediction error has established itself at the heart of formal models of animal learning and current hypotheses of dopamine function. Several interpretations of prediction error have been offered, including the model-free reinforcement learning method known as temporal difference learning (TD), and the important Rescorla-Wagner (RW) learning rule. Here, we present a model-based adaptation of these ideas that provides a good account of empirical data pertaining to dopamine neuron firing patterns and associative learning paradigms such as latent inhibition, Kamin blocking and overshadowing. Our departure from model-free reinforcement learning also offers: 1) a parsimonious distinction between tonic and phasic dopamine functions; 2) a potential generalization of the role of phasic dopamine from valence-dependent "reward" processing to valence-independent "salience" processing; 3) an explanation for the selectivity of certain dopamine manipulations on motivation for distal rewards; and 4) a plausible link between formal notions of prediction error and accounts of disturbances of thought in schizophrenia (in which dopamine dysfunction is strongly implicated). The model distinguishes itself from existing accounts by offering novel predictions pertaining to the firing of dopamine neurons in various untested behavioral scenarios.

Action Potentials↗
PubMed2001

Amygdala lesion in temporal lobe epilepsy subjects impairs associative learning of emotional facial expressions.

To investigate the role of unilateral amygdala lesions on processing emotions, 22 drug-resistant temporal lobe epilepsy (TLE) subjects (12 with left-sided and ten with right-sided focus) were tested, after anterior temporal lobectomy or selective amygdalo-hippocampectomy on two associative learning tasks containing emotional and neutral facial expressions, respectively. Volumetric lesion analysis was performed on the basis of 3-D MR images. No effects of lesion side were found in TLE subjects. Taken the extent of amygdala damage into account, an interaction effect could be shown between task (learning of neutral facial expressions versus emotional facial expressions) and group (subjects with little versus considerable amygdala damage), indicating worse performance of subjects with considerable amygdala damage in learning emotional facial expressions. Subjects with considerable amygdala damage were also significantly impaired in learning emotional facial expressions when compared with control subjects.

Adult↗
PubMed1988

Parametric features of inhibition of feeding in Aplysia by associative learning, satiation, and sustained lip stimulation.

In order to determine whether different classes of behavioral plasticity affect common or unique neural loci, the effects of three types of processes that inhibit feeding in Aplysia were quantified. Changes in feeding behavior due to an associative learning task in which animals learn that food is inedible were compared with behavioral effects caused by satiation and by sustained lip stimulation. The data indicate that each process modifying feeding can be characterized by differences in time to stop responding to food, by differences in specificity of the decrement to a particular food, and by different patterns of motor output before complete cessation of responsiveness. The data suggest each process inhibiting feeding acts at a different neural site. Learning that food is inedible may be due to facilitation of a specific sensory pathway onto pattern generators producing rejection responses. Sustained lip stimulation seems to inhibit feeding by causing a decrement in all outputs of a particular sensory pathway. Finally, satiation appears to represent inhibition of feeding motor elements.

Animals↗
PubMedDate not supplied

Mapping of olfactory memory circuits: region-specific c-fos activation after odor-reward associative learning or after its retrieval.

Although there is growing knowledge about intracellular mechanisms underlying neuronal plasticity and memory consolidation and reconsolidation after retrieval, information concerning the interaction among brain areas during formation and retrieval of memory is relatively sparse and fragmented. Addressing this question requires simultaneous monitoring of activity in multiple brain regions during learning, the post-acquisition consolidation period, and retrieval and subsequent reconsolidation. Immunoreaction to the immediate early gene c-fos is a powerful tool to mark neuronal activation of specific populations of neurons. Using this method, we are able to report, for the first time, post-training activation of a network of closely related brain regions, particularly in the frontal cortex and the basolateral amygdala (BLA), that is specific to the learning of an odor-reward association. On the other hand, retrieval of a well-established associative memory trace does not seem to differentially activate the same regions. The amygdala, in particular, is not engaged after retrieval, whereas the lateral habenula (LHab) shows strong activation that is restricted to animals having previously learned the association. Although intracellular mechanisms may be similar during consolidation and reconsolidation, this study indicates that different brain circuits are involved in the two processes, at least with respect to a rapidly learned olfactory task.

Amygdala↗
PubMed1999

Guanfacine and clonidine, alpha 2-agonists, improve paired associates learning, but not delayed matching to sample, in humans.

The present study compares the effects of two alpha 2-agonists, clonidine (0.5, 2, and 5 micrograms/kg, p.o.) and guanfacine (7 and 29 micrograms/kg, p.o.) in young healthy volunteers on their performance in visual paired associates learning (PAL) and delayed matching to sample (DMTS) visual short-term recognition memory tests. In the PAL test, clonidine 2 and guanfacine 29 micrograms/kg improved the subjects' performance. In the DMTS test, clonidine at 5 micrograms/kg delay-dependently impaired performance accuracy, and at 2 and 5 micrograms/kg it also slowed responses. Guanfacine had no effect on DMTS test performance. Clonidine 5 and guanfacine 29 micrograms/kg equally increased subjective feelings of sedation and reduced blood pressure. The results suggest that both clonidine and guanfacine facilitated PAL learning by improving "frontal strategies," but only clonidine disrupted "mneomonic processing" decreasing DMTS accuracy. The greater selectivity of guanfacine for alpha 2A-adrenoceptor subtype may explain the different profile of action of the drugs.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2003

Identification of nuclear/nucleolar localization signal in Aplysia learning associated protein of slug with a molecular mass of 18 kDa homologous protein.

We isolated a learning associated protein of slug with a molecular mass of 18 kDa (LAPS18) homologue from the expressed sequence tag database of Aplysia kurodai and named it Aplysia LAPS18-like protein (ApLLP). ApLLP encodes 120 amino acids and has 57% identity with LAPS18. To examine the subcellular expression pattern of ApLLP we constructed an EGFP-tagged ApLLP fusion protein and overexpressed it in both Aplysia neurons and COS-7 cells. In contrast to the previous findings, which showed that LAPS18 is secreted by COS-7 cells, ApLLP-EGFP was localized to the nucleus, and most of it to nucleoli. Analysis of deletion mutants of ApLLP-EGFP showed that the N-terminal and the C-terminal nucleolar and nucleus localization signal sequences are important for localization to the nucleus and the nucleoli.

Animals↗
PubMed2007

The role of similarity in human associative learning.

In 2 experiments, humans received sequences of patterns that were similar (AX-->BX, AY-->BY, AZ-->BZ) or dissimilar (CX-->DY, CY-->DZ, CZ-->DX). The patterns were portrayed as bugs that could be eliminated with 2 insecticide sprays (red or blue). Either spray eliminated bugs with Features A and C, and participants learned by trial and error to use one spray (e.g., red) to eliminate bugs with Feature B and the other spray (e.g., blue) to eliminate those with Feature D. In Experiment 1, participants' spray choice for bugs with Feature A came to match that used to eliminate bugs with Feature B, but there was no such associative transfer between Features C and D. That is, similarity promoted associative transfer of responding between paired patterns when the features used to manipulate similarity (i.e., X, Y, and Z) were irrelevant. In Experiment 2, in which X, Y, and Z were relevant to the solution of configural discrimination, similarity hindered such associative transfer. These results complement those found in pigeons (R. A. Rescorla & D. J. Gillan, 1980) and indicate that similarity should not be accorded independent status as a principle of associative learning.

Association Learning↗
PubMed1982

Primary changes of membrane currents during retention of associative learning.

A single identified neuron was repeatedly isolated by axotomy from the central nervous system of the nudibranch mollusk Hermissenda crassicornis. An early voltage-dependent outward K+ current of this neuron was reduced and more rapidly inactivated for animals previously trained with paired but not randomized light and rotation. Since this current change can affect interneuron and motorneuron output via known synaptic pathways, it helps explain a long-lasting behavioral change that shows the defining features of vertebrate associative learning.

Animals↗
PubMed1981

One-trial associative learning modifies food odor preferences of a terrestrial mollusc.

We present evidence of rapid and reliable associative learning by the terrestrial mollusc, Limax maximus. Slugs were exposed once to a pairing of a highly attractive food odor (potato or carrot) and a saturated solution of quinidine sulfate, a bitter-tasting plant substance. In comparison with control slugs, the exposed slugs subsequently displayed a markedly reduced preference for the odor paired with quinidine. This reduced odor preference was limited to the specific odor paired with quinidine and did not generalize to other food odors.

Journal Article↗
PubMed1996

The nitric oxide synthesis inhibitor L-NAME facilitates associative learning.

1. Nitric oxide has been suggested to play an important role in synaptic plasticity and in learning. 2. The authors examined the effects of NW-nitro-L-arginine methyl ester, a competitive and enantiomeric specific inhibitor of nitric oxide synthase, on classical conditioning of the rabbit's nictitating membrane response. 3. It was found that L-NAME significantly enhanced the acquisition of conditioned responses. 4. The enhanced conditioned responses were not due to a sensitization of the conditioned and unconditioned reflexes or to changes in baseline levels of responding. 5. The dose and route of administration of L-NAME employed in this study had no effect on blood pressure. 6. These results suggest that nitric oxide normally functions as a tonic inhibitory modulator of associative learning and that procedures aimed at decreasing its production may provide a novel approach for improving learning.

Animals↗
PubMed2002

Nefiracetam ameliorates associative learning impairment in the scopolamine-injected older rabbit.

BACKGROUND: The cognition-enhancing drug, nefiracetam, is in Phase III clinical trials to treat memory impairment in Alzheimer's disease (AD). Nefiracetam ameliorates acquisition of delay eyeblink classical conditioning in older rabbits, a form of associative learning with striking behavioral and neurobiological similarities in rabbits and humans. In both species, delay eyeblink conditioning engages the septo-hippocampal cholinergic system and is disrupted when the cholinergic system is antagonized. Delay eyeblink classical conditioning is impaired in normal aging and severely disrupted in AD. MATERIAL/METHODS: To test further the efficacy of nefiracetam in an animal model that mimics some of the neurobiological and behavioral effects present in AD, we tested 56 older rabbits assigned to 7 treatment groups in the 750 ms delay eyeblink conditioning procedure. Older rabbits were injected with 1.5 mg/kg scopolamine to simulate disruption of the cholinergic system in AD. Three doses of nefiracetam (5, 10, or 15 mg/kg) were also injected in older rabbits receiving 1.5 mg/kg scopolamine. Control groups were treated with 1.5 mg/kg scopolamine + vehicle, vehicle alone, or explicitly unpaired presentations of conditioning stimuli and vehicle or 1.5 mg/kg scopolamine + 15 mg/kg nefiracetam. RESULTS: Rabbits injected with 1.5 mg/kg scopolamine alone were impaired, but a dose of 15 mg/kg nefiracetam reversed significantly the behavioral impairment. CONCLUSIONS: Nefiracetam had ameliorating effects on a task impaired in AD in an animal model of AD: older rabbits with cholinergic system antagonism.

Aging↗
PubMed1987

Cerebellar GABAergic processes: evidence for critical involvement in a form of simple associative learning in the rabbit.

Converging evidence from electrophysiological recording and lesion studies suggests an essential role for the cerebellum in classical conditioning of the nictitating membrane response in the rabbit. The present study begins to delineate within this structure neurotransmitter systems that appear critical for the expression of this form of simple associative learning. Experiments reported here demonstrate that microinfusion of gamma-aminobutyric acid (GABA) antagonists (either bicuculline methiodide or picrotoxin) into specific areas of the medial dentate/lateral interpositus nuclei or into the cerebellar cortex of lobule HVI can selectively and reversibly abolish conditioned responding, while leaving the unconditioned reflex response intact. The results are consistent with the suggestion that GABAergic synapses play an essential role in the circuitry that mediates the conditioned response.

Animals↗
PubMed1994

A system for quantitative analysis of associative learning. Part 1. Hardware interfaces with cross-species applications.

This paper describes a reliable, durable, and readily calibrated hardware interface system designed to present sensory stimuli at precise time intervals and to transduce and digitize behavioral data in classical conditioning experiments. It has been extensively tested in a 'model'-associative learning task, conditioning of eyeblink or nictitating membrane responses, but is readily adapted to other behavioral paradigms. Each system can run a pair of conditioned experimental or pseudoconditioned control subjects simultaneously, or collect data from a single subject carrying out two tasks simultaneously. The requirements of the system are defined, based around an inexpensive AT-class MS-DOS microcomputer. The interface hardware needed to present auditory tone conditioned stimuli and corneal airpuff-unconditioned stimuli to training subjects are detailed, with timing signals provided by TTL pulses generated at the digital output ports of an analog-to-digital (A/D) converter. An electronic circuit is described that provides stable inputs to the A/D converter, transducing eyeblink responses to voltage signals opto-electronically, without requiring any invasive attachment of the subject to the subject to the measuring device. The 1-piece eyeblink sensor used (selected for ease of alignment and maintenance) is also discussed. Examples of applications for classical conditioning of rabbits, rats, and human subjects are described. A companion paper describes data-acquisition and control software written as a user-friendly interface for this hardware system.

Animals↗