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PubMed1983

One-trial associative learning by an isolated molluscan CNS: use of different chemoreceptors for training and testing.

An isolated preparation of the lips, cerebral ganglia and buccal ganglia of the terrestrial slug, Limax maximus, can display one-trial associative learning. The lip-brain preparation can learn to suppress feeding motor program responses to lip stimulation with a standard food extract after a single pairing of food extract and quinidine stimulation to the isolated lips. Learning can occur with training stimuli applied to one lip and testing stimuli applied to the opposite, "naive' lip. Learning can also occur if the food extract and quinidine are applied during training to opposite lips. These results indicate that the synaptic alteration due to learning occurs in the CNS, not at the sensory periphery.

Animals↗
PubMed1998

Effects of D-AP5 and NMDA microiontophoresis on associative learning in the barrel cortex of awake rats.

Experiments involving single-unit recordings and microiontophoresis were carried out in the barrel cortex of awake, adult rats subjected to whisker pairing, an associative learning paradigm where deflections of the recorded neuron's principle vibrissa (S2) are repeatedly paired with those of a non-adjacent one (S1). Whisker pairing with a 300 ms interstimulus interval was applied to 61 cells. In 23 cases, there was no other manipulation whereas in the remaining 38, pairing occurred in the presence of one of three pharmacological agents previously shown to modulate learning, receptive field plasticity and long-term potentiation: N-methyl-D-aspartic acid (NMDA) (n=8), the NMDA receptor antagonist AP5 (n=17) or the nitric oxide synthase inhibitor L-nitro-arginine-N-methyl-ester (L-NAME) (n=13). Non-associative (unpaired) experiments (n=14) and delivery of pharmacological agents without pairing (n=14) served as controls. Changes in neuronal responsiveness to S1 following one of these procedures were calculated and adjusted relative to changes in the responses to S2. On average, whisker pairing alone yielded a 7% increase in the responses to S1. This enhancement differed significantly from the 17% decrease obtained in the non-associative control condition and could not be attributed to variations in the state of the animals because analysis of the cervical and facial muscle electromyograms revealed that periods of increased muscular activity, reflecting heightened arousal, were infrequent (less than 4% of a complete experiment on average) and occurred randomly. The enhancement of the responses to S1 was further increased when whisker pairing was performed in the presence of L-NAME (27%) or NMDA (35%) whereas AP5 reduced it to 1%. During the delivery period, NMDA enhanced both neuronal excitability and responsiveness to S1 whereas AP5 depressed them. However, the effects of both substances disappeared immediately after administration had ended. L-NAME did not affect the level of ongoing activity and responses to S1 significantly. From these data, we concluded that, since the changes in the responses to S1 lasted longer than the periods of both whisker pairing and drug delivery, they were not residual excitatory or inhibitory drug effects on neuronal excitability. Thus, our results indicate that, relative to the unpaired controls, whisker pairing led to a 24% increase in the responsiveness of barrel cortex neurons to peripheral stimulation and that these changes were modulated by the local application of pharmacological agents that act upon NMDA receptors and pathways involving nitric oxide. We can infer that somatosensory cerebral cortex is one site where plasticity emerges following whisker pairing.

2-Amino-5-phosphonovalerate↗
PubMed1986

Cholinergic suppression: a postsynaptic mechanism of long-term associative learning.

Food avoidance learning in the mollusc Pleurobranchaea entails reduction in the responsiveness of key brain interneurons in the feeding neural circuitry, the paracerebral feeding command interneurons (PCNs), to the neurotransmitter acetylcholine (AcCho). Food stimuli applied to the oral veil of an untrained animal depolarize the PCNs and induce the feeding motor program (FMP). Atropine (a muscarinic cholinergic antagonist) reversibly blocks the food-induced depolarization of the PCNs, implicating AcCho as the neurotransmitter mediating food detection. AcCho applied directly to PCN somata depolarizes them, indicating that the PCN soma membrane contains AcCho receptors and induces the FMP in the isolated central nervous system preparation. The AcCho response of the PCNs is mediated by muscarinic-like receptors, since comparable depolarization is induced by muscarinic agonists (acetyl-beta-methylcholine, oxotremorine, pilocarpine), but not nicotine, and blocked by muscarinic antagonists (atropine, trifluoperazine). The nicotinic antagonist hexamethonium, however, blocked the AcCho response in four of six cases. When specimens are trained to suppress feeding behavior using a conventional food-avoidance learning paradigm (conditionally paired food and shock), AcCho applied to PCNs in the same concentration as in untrained animals causes little or no depolarization and does not initiate the FMP. Increasing the concentration of AcCho 10-100 times, however, induces weak PCN depolarization in trained specimens, indicating that learning diminishes but does not fully abolish AcCho responsiveness of the PCNs. This study proposes a cellular mechanism of long-term associative learning--namely, postsynaptic modulation of neurotransmitter responsiveness in central neurons that could apply also to mammalian species.

Acetylcholine↗
PubMed1978

Paired associate learning in early infantile autism and receptive developmental aphasia.

A comparative study of nonverbal MA matched groups of five autistic, five aphasic, five normal and five retarded children was made on an auditory-visual and a visual-visual paired-associate learning task. The results showed that, although the autistic and receptive aphasic children were both unable to associate sounds with their visual counterparts at the same rate as normal children, the aphasic children overcame this deficit at a significantly faster rate than autistic children. This study pinpoints one dysfunction that could subsume the severe verbal comprehension defect in autistic and aphasic children.

Adolescent↗
PubMed2001

The relationship between paired associate learning and phonological skills in normally developing readers.

Seventy-five 6- to 11-year-old children were administered tests of phonological awareness, verbal short term memory (STM), and visual-verbal paired associate learning (PA learning) to investigate their relationship with word recognition and decoding skills. Phonological awareness was a stronger concurrent predictor of word recognition than verbal STM, and phonological awareness but not verbal STM was a predictor of learning in the PA learning task. Importantly, measures of phonological awareness and PA learning both accounted for independent variance in word reading, even when decoding skill was controlled. The results suggest that PA learning and phonological awareness tasks tap two separate mechanisms involved in learning to read. The results are discussed in relation to current theories of reading development.

Child↗
PubMed2004

Egocentric conditional associative learning: effects of restricted lesions to the hippocampo-mammillo-thalamic pathway.

Rats with lesions of the hippocampus, the mammillary region, the anterior thalamic nuclei, and normal control animals were trained on a conditional associative learning task in which they had to learn to make one of two motor responses (i.e., turn left or right), depending on which one of two visual cues was presented. Damage to the hippocampus severely impaired performance of this task. By contrast, rats with lesions of the mammillary region or the anterior thalamic nuclei were able to acquire the task at a rate comparable to that of the normal animals. These findings demonstrate that hippocampal lesions impair the ability to form arbitrary associations between visual cues and kinesthetic responses (body turns) and, furthermore, suggest that the hippocampus does not rely on input from its major subcortical targets for learning such visual-kinesthetic associations.

Animals↗
PubMed2000

Effects of prolonged ethanol exposure on neurophysiological measures during an associative learning paradigm.

Long-term ethanol exposure has been reported to produce electrophysiological and cognitive impairments in some alcoholics. This study assessed the effects of chronic ethanol exposure on neurophysiological indices of associative learning in rats. Male Wistar rats (46) were exposed to ethanol vapor (EtOH group) or air (control group) for 6 consecutive weeks. After the animals were withdrawn from ethanol, electrodes were implanted in the frontal and parietal cortices and in the amygdala. Following a prolonged abstinence from ethanol (10-15 weeks), rats were exposed to a classical conditioning paradigm in which a food pellet was paired with the presentation of an auditory stimulus. During the first five sessions (conditioning phase), food pellet presentation was paired with the presentation of an infrequently presented tone. During the second five sessions (extinction phase), the association between food pellet presentation and the infrequently presented tone was weakened by no longer presenting food pellets following the infrequent tone. During selected test sessions, event-related brain potentials (ERPs) elicited by each tone (i.e. food-paired tone, non-paired tone) were recorded and analyzed. These analyses revealed differences in ERP responses between the groups. The latency of the N1 and P2 ERP components in the cortex of the control group, but not the EtOH group, increased during sessions when the association between food pellet delivery and tone presentation was being established or extinguished. These data support the hypothesis that chronic ethanol treatment results in a loss of responsivity in ERP components sensitive to changes in food-tone associations, even following a prolonged period of withdrawal from ethanol.

Acoustic Stimulation↗
PubMed1981

The effects of perceived control on the paired-associate learning of elderly persons.

Forty-five elderly subjects performed a modified paired-associate learning task under two conditions designed to enhance their perception of control. Subjects in enhanced control conditions chose their own response items ("choice" subjects) or were allowed to manually control response interval duration ("self-paced"). Yoked controls learned the same items selected by choice subjects, or experienced pacing conditions under which they were allowed comparable amounts of response time. The design was an incomplete 2 x 3 x 6 factorial with two types of item selection (choice vs. force), three types of pacing (self-paced, yoked item-by-item, yoke by trial median time), and six trials. There was no "choice" group in the "item yoked" pacing condition. As predicted, subjects experiencing either or both of the control-enhancing conditions performed better than yoked controls. Experiencing both item choice and self-pacing did not result in performance which was significantly better than that of subjects experiencing only one or the other. Results are discussed in light of previous work with young persons, and recommendations are offered to researchers.

Aged↗
PubMed1997

The role of an amygdalo-nigrostriatal pathway in associative learning.

The present study examined the role of an amygdalo-nigrostriatal pathway in associative learning. An asymmetrical lesion model was used to test whether a circuit from the amygdala central nucleus to the dorsolateral striatum, via the substantia nigra, is critical for mediating conditioned orienting responses. Rats with an asymmetrical lesion, consisting of neurotoxic removal of central nucleus neurons in one hemisphere and depletion of the dopamine innervation of the dorsolateral striatum in the contralateral hemisphere, failed to acquire conditioned orienting responses. In contrast, the asymmetrical lesion had no effect on spontaneous orienting or learning another response directed to the source of the food unconditioned stimulus in the same task. A second experiment tested the effect of reversible inactivation of the dorsolateral striatum contralateral to a neurotoxic central nucleus lesion on acquisition of the conditioned orienting response. Although inactivation did not affect spontaneous orienting, rats failed to acquire the conditioned orienting response during sessions in which inactivation occurred. Immediately after the inactivation procedure was terminated, however, a significant increase in orienting to the conditioned stimulus was evident. These data support the interpretation that the dorsolateral striatum provides a route for the expression of the conditioned orienting response but is not essential for acquisition of this learned behavior.

Amygdala↗
PubMed1984

[The observational learning in mentally retarded children: the effects of mediational sentences on paired-associate learning].

Thirty-eight mentally retarded children and 44 normal children learned a paired-associate picture list under one of four conditions. Subjects in E1 group were exposed to the model who learned the same list by means of formulating mediational sentences directly prior to learning by themselves. Subjects in E2 group were exposed to the model who learned the different list by means of formulating mediational sentences. Subjects in E3 group were exposed to the model who learned the same list without mediational sentences. control subjects learned the paired-associate list without observing the model. The results indicated that retarded and normal subjects in E1 group performed significantly higher than subjects in E2, E3, and control groups. The modeling of verbal elaboration was proved.

Child, Preschool↗
PubMed1991

A role for protein kinase C in associative learning.

Recent work suggests that protein kinase C (PKC), an enzyme that has a critical role in the regulation of cell growth and differentiation, also participates in the sequence of molecular events that underlie learning and memory. By means of electrophysiological, biochemical, and neuro-imaging methods it has been demonstrated that, in the brain, the distribution of PKC changes as a result of memory storage. The changes in distribution occur within the same ensembles of nerve cells that are necessary for the acquisition and performance of various learning tasks in several species. Here we review the data pertaining to a model that has been proposed to account for the participation of PKC as a molecular signal for cotemporal synaptic input during associative learning.

Alzheimer Disease↗
PubMed1995

Amygdala role in conditioned associative learning.

Amygdala role in emotion was reviewed in reference to recent amygdala lesion studies and neuronal responses in the rat amygdala to conditioned stimuli. Extensive lesion studies suggest that the amygdala is crucial in various kinds of motivated and emotional behavior, and related autonomic responses. These amygdala functions critically depend on learning and memory. Amygdala lesions, both before and after training of conditioned associative learning, impaired emotional expression without simple sensory-motor deficits. Pharmacological experiments indicated neurotransmission in the amygdala is mediated through NMDA and AMPA receptors. These results strongly suggest the amygdala involvement in acquiring and storing associative memory (i.e. stimulus-affect association), by which animals recognize and evaluate the biological significance of a stimulus. This information is then transferred to the brainstem executing system. In the neurophysiological experiments, there were topographic distributions of sensory-responsive neurons within the amygdala, which were well correlated to anatomical data. The responses of rat amygdala neurons changed plastically during learning. Furthermore, more sensory-responsive neurons were encountered in the amygdala of rats trained to associate the sensory stimuli with a reinforcement than in the amygdala of rats that were not trained. In trained rats, multimodal neurons that responded to conditioned and unconditioned stimuli were frequently found in the basolateral and central nuclei of the amygdala. The results suggest that basolateral and central nuclei are foci where various sensory modalities converge, and which might perform critical functions in acquiring and storing long-term associative memory to link between sensory information and affective significance.

Amygdala↗
PubMed2006

Associative learning: the instructive function of biogenic amines.

Biogenic amines like dopamine or octopamine modify neural function at multiple levels, sensitizing or depressing behaviour. Recent studies in insects have now shown that, besides a role in motivational modulation, biogenic amines substitute the reinforcer function in associative learning, thus instructing the nervous system about the relevance of external events.

Animals↗
PubMed2004

Modeling a task that is sensitive to dementia of the Alzheimer's type: individual differences in acquisition of a visuo-spatial paired-associate learning task in rhesus monkeys.

Early detection of progressive diseases such as Alzheimer's Disease (AD) is crucial for both the treatment and study of the disease. Performance on a visuo-spatial paired-associates learning (vsPAL) task was recently shown to reliably predict a diagnosis of AD in aged populations. The present study reports the development of this vsPAL task for use in nonhuman primates. Translation of vsPAL to a nonhuman model may provide improved preclinical tools for study of the etiology and treatment of dementia. Twelve young adult male rhesus monkeys were trained to perform the vsPAL task concurrently with tests comprising a nonhuman primate neuropsychological test battery. Monkeys successfully learned to perform vsPAL and did so in a task-difficulty ranked fashion. Despite significant individual differences in capability in the acquisition of the recognition memory aspects of the task, all monkeys evidenced the ability to learn within-trial, i.e. to improve with repeated stimulus-location pairings. These results support the use of vsPAL performance under various challenge conditions to investigate the possible substrates of early cognitive decline in AD. Comparison of performance on vsPAL with performance on other memory tasks in the battery will be of more general use in differentiating mechanisms involved in various aspects of mnemonic function.

Alzheimer Disease↗
PubMed2004

Cuttlefish (Sepia officinalis: Cephalopoda) hunting behavior and associative learning.

Because most learning studies in cephalopods have been performed on octopods, it remains unclear whether such abilities are specific to octopus, or whether they correlate with having a larger and more centrally organized brain. To investigate associative learning in a different cephalopod, six sexually mature cuttlefish (Sepia officinalis) participated in a counterbalanced, within-subjects, appetitive, classical conditioning procedure. Two plastic spheres (conditioned stimuli, CSs), differing in brightness, were presented sequentially. Presentation of the CS+ was followed 5 s later by a live feeder fish (unconditioned stimulus, US). Cuttlefish began to attack the CS+ with the same type of food-acquisition seizures used to capture the feeder fish. After seven blocks of training (42 presentations of each CS) the difference in seizure probability between CS+ and CS- trials more than doubled; and was found to be significantly higher in late versus early blocks. These results indicate that cuttlefish exhibit autoshaping under some conditions. The possible ecological significance of this type of learning is briefly discussed.

Animals↗
PubMed2006

G(o) signaling is required for Drosophila associative learning.

Heterotrimeric G(o) is one of the most abundant proteins in the brain, yet relatively little is known of its neural functions in vivo. Here we demonstrate that G(o) signaling is required for the formation of associative memory. In Drosophila melanogaster, pertussis toxin (PTX) is a selective inhibitor of G(o) signaling. The postdevelopmental expression of PTX within mushroom body neurons robustly and reversibly inhibits associative learning. The effect of G(o) inhibition is distributed in both gamma- and alpha/beta-lobe mushroom body neurons. However, the expression of PTX in neurons adjacent to the mushroom bodies does not affect memory. PTX expression also does not interact genetically with a rutabaga adenylyl cyclase loss-of-function mutation. Thus, G(o) defines a new signaling pathway required in mushroom body neurons for the formation of associative memory.

Adenylyl Cyclases↗
PubMedDate not supplied

A role for Synapsin in associative learning: the Drosophila larva as a study case.

Synapsins are evolutionarily conserved, highly abundant vesicular phosphoproteins in presynaptic terminals. They are thought to regulate the recruitment of synaptic vesicles from the reserve pool to the readily-releasable pool, in particular when vesicle release is to be maintained at high spiking rates. As regulation of transmitter release is a prerequisite for synaptic plasticity, we use the fruit fly Drosophila to ask whether Synapsin has a role in behavioral plasticity as well; in fruit flies, Synapsin is encoded by a single gene (syn). We tackled this question for associative olfactory learning in larval Drosophila by using the deletion mutant syn(97CS), which had been backcrossed to the Canton-S wild-type strain (CS) for 13 generations. We provide a molecular account of the genomic status of syn(97CS) by PCR and show the absence of gene product on Western blots and nerve-muscle preparations. We found that olfactory associative learning in syn(97CS) larvae is reduced to approximately 50% of wild-type CS levels; however, responsiveness to the to-be-associated stimuli and motor performance in untrained animals are normal. In addition, we introduce two novel behavioral control procedures to test stimulus responsiveness and motor performance after "sham training." Wild-type CS and syn(97CS) perform indistinguishably also in these tests. Thus, larval Drosophila can be used as a case study for a role of Synapsin in associative learning.

Animals↗