Changes In Associative Learning Research Articles

Dopamine-mediated striatal activity and function is enhanced in GlyRα2 knockout animals

The glycine receptor alpha 2 (GlyRα2) is a ligand-gated ion channel which upon activation induces a chloride conductance. Here, we investigated the role of GlyRα2 in dopamine-stimulated striatal cell activity and behavior. We show that depletion of GlyRα2 enhances dopamine-induced increases in the activity of putative dopamine D1 receptor-expressing striatal projection neurons, but does not alter midbrain dopamine neuron activity. We next show that the locomotor response to d-amphetamine is enhanced in GlyRα2 knockout animals, and that this increase correlates with c-fos expression in the dorsal striatum. 3-D modeling revealed an increase in the neuronal ensemble size in the striatum in response to D-amphetamine in GlyRα2 KO mice. Finally, we show enhanced appetitive conditioning in GlyRα2 KO animals that is likely due to increased motivation, but not changes in associative learning or hedonic response. Taken together, we show that GlyRα2 is an important regulator of dopamine-stimulated striatal activity and function.

Low Perceived Self-Efficacy Impedes Discriminative Fear Learning

Perceived self-efficacy refers to a subject’s expectation about the outcomes his/her behavior will have in a challenging situation. Low self-efficacy has been implicated in the origins and maintenance of phobic behavior. Correlational studies suggest an association between perceived self-efficacy and learning. The experimental manipulation of perceived self-efficacy offers an interesting approach to examine the impact of self-efficacy beliefs on cognitive and emotional functions. Recently, a positive effect of an experimentally induced increased self-efficacy on associative learning has been demonstrated. Changes in associative learning constitute a central hallmark of pathological fear and anxiety. Such alterations in the acquisition and extinction of conditioned fear may be related to cognitive and neurobiological factors that predict a certain vulnerability to anxiety disorders. The present study builds on previous own work by investigating the effect of an experimentally induced low perceived self-efficacy on fear acquisition, extinction and extinction retrieval in a differential fear conditioning task. Our results suggest that a negative verbal feedback, which leads to a decreased self-efficacy, is associated with changes in the acquisition of conditioned fear. During fear acquisition, the negative verbal feedback group showed decreased discrimination of fear responses between the aversive and safe conditioned stimuli (CS) relative to a group receiving a neutral feedback. The effects of the negative verbal feedback on the acquisition of fear discrimination learning were indexed by an impaired ability to discriminate the probability of receiving a shock during acquisition upon presentation of the aversive (CS+) relative to the safe stimuli (CS−). However, the effects of low self-efficacy on discrimination learning were limited to fear acquisition. No differences between the groups were observed during extinction and extinction retrieval. Furthermore, analysis of other outcome measures, i.e., skin conductance responses and CS valence ratings, revealed no group differences during the different phases of fear conditioning. In conclusion, lower perceived self-efficacy alters cognitive/expectancy components of discrimination during fear learning but not evaluative components and physiological responding. The pattern of findings suggests a selective, detrimental role of low(er) self-efficacy on the subject’s ability to learn the association between ambiguous cues and threat/safety.

Associative learning changes cross-modal representations in the gustatory cortex.

A growing body of literature has demonstrated that primary sensory cortices are not exclusively unimodal, but can respond to stimuli of different sensory modalities. However, several questions concerning the neural representation of cross-modal stimuli remain open. Indeed, it is poorly understood if cross-modal stimuli evoke unique or overlapping representations in a primary sensory cortex and whether learning can modulate these representations. Here we recorded single unit responses to auditory, visual, somatosensory, and olfactory stimuli in the gustatory cortex (GC) of alert rats before and after associative learning. We found that, in untrained rats, the majority of GC neurons were modulated by a single modality. Upon learning, both prevalence of cross-modal responsive neurons and their breadth of tuning increased, leading to a greater overlap of representations. Altogether, our results show that the gustatory cortex represents cross-modal stimuli according to their sensory identity, and that learning changes the overlap of cross-modal representations.

The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an “inverted V” dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

Associative Learning Changes the Organization of Functional Excitatory Circuits Targeting the Supragranular Layers of Mouse Barrel Cortex

In primary sensory cortices, neuronal circuits change throughout life as a function of learning. During associative learning a neutral sensory stimulus acquires the emotional valence of an aversive event or a reward after repetitive contingent pairing. One important consequence is the enlargement of the representational area of the conditioned stimulus in the cortical map of its sensory modality. The details of this phenomenon at the circuit level are still largely unknown. Here, mice were trained in a differential conditioning paradigm where the deflections of one whisker row were paired with tail shocks and the deflections of two others were not. Changes occurring in excitatory circuits of barrel cortex were then examined in brain slices with laser scanning photostimulation mapping. We found that learning affected the projections targeting the supragranular layers in the columns of unpaired whiskers: Pyramidal cells located in layer (L) 3 received enhanced inputs from L5A cells located in their home column and new inputs from L2/3 and L4 cells located in the neighboring column of the paired whisker. In contrast, the excitatory projections impinging onto L2/3 cells in the column of the paired whisker were not altered. Together, these data reveal that associative learning alters the canonical columnar organization of functional ascending L4 projections and strengthens transcolumnar excitatory projections in barrel cortex. These phenomena could participate to the transformation of the whisker somatotopic map induced by associative learning.

A neural model of hippocampal–striatal interactions in associative learning and transfer generalization in various neurological and psychiatric patients

Building on our previous neurocomputational models of basal ganglia and hippocampal region function (and their modulation by dopamine and acetylcholine, respectively), we show here how an integration of these models can inform our understanding of the interaction between the basal ganglia and hippocampal region in associative learning and transfer generalization across various patient populations. As a common test bed for exploring interactions between these brain regions and neuromodulators, we focus on the acquired equivalence task, an associative learning paradigm in which stimuli that have been associated with the same outcome acquire a functional similarity such that subsequent generalization between these stimuli increases. This task has been used to test cognitive dysfunction in various patient populations with damages to the hippocampal region and basal ganglia, including studies of patients with Parkinson’s disease (PD), schizophrenia, basal forebrain amnesia, and hippocampal atrophy. Simulation results show that damage to the hippocampal region—as in patients with hippocampal atrophy (HA), hypoxia, mild Alzheimer’s (AD), or schizophrenia—leads to intact associative learning but impaired transfer generalization performance. Moreover, the model demonstrates how PD and anterior communicating artery (ACoA) aneurysm—two very different brain disorders that affect different neural mechanisms—can have similar effects on acquired equivalence performance. In particular, the model shows that simulating a loss of dopamine function in the basal ganglia module (as in PD) leads to slow acquisition learning but intact transfer generalization. Similarly, the model shows that simulating the loss of acetylcholine in the hippocampal region (as in ACoA aneurysm) also results in slower acquisition learning. We argue from this that changes in associative learning of stimulus–action pathways (in the basal ganglia) or changes in the learning of stimulus representations (in the hippocampal region) can have similar functional effects.

Age-related changes in associative learning for olfactory and visual stimuli in rodents.

Memory for olfactory stimuli may be particularly affected by age-related brain changes in humans and may be an early indicator of cognitive impairment and Alzheimer's disease. Studies involving rats have offered insights into impaired cognition in aged animals, but few have examined odor memory. Therefore, it is unclear whether aged rats are a good model for possible age-related changes in odor memory in humans. Young (6-month-old) and old (24-month-old) rats were tested on associative learning tasks involving visual and olfactory stimuli. The first task examined age-related differences in discrimination and reversal learning for olfactory and visual stimuli; the second task utilized an associative contextual learning task involving olfactory and visual cues. Although old rats were able to perform the olfactory and visual discrimination tasks as well as young rats, old rats displayed significant age-related impairment on the reversal learning and contextual learning tasks. The results suggest that aging may have a similar deleterious effect on odor memory in rats and in humans. The findings may have important implications for the selection of memory paradigms for future research studies on aging. In addition, the use of an animal model to investigate the effects of aging on odor memory will allow researchers the ability to investigate how age-related neuroanatomical and neurochemical changes may result in impaired odor memory.

A stress-induced anxious state in male rats: Corticotropin-releasing hormone induces persistent changes in associative learning and startle reactivity

Exposure to intense inescapable stressors induces a persistent anxious state in rats. The anxious state is evident as increased sensory reactivity and enhanced associative learning. We examine whether similar neurobehavioral changes are observed after intracerebroventricular (ICV) administration of corticotropin releasing hormone (CRH). Two behaviors were observed: acoustic startle responses (ASRs) and acquisition of the classically conditioned eyeblink response. Male Sprague-Dawley rats were administered ICV CRH either in a single dose (1.0 microg/rat) or in three doses each separated by 30 min. Exaggerated ASRs were evident 2 hours after either CRH treatment; however, only the rats given three injections exhibited a persistently exaggerated ASR apparent 24 hours after CRH treatment. Rats administered three injections of CRH also exhibited faster acquisition of the eyeblink conditioned response beginning 24 hours after treatment. Yet, we did not find evidence for a persistent activation of the HPA-axis response; three CRH injections did not lead to elevated basal plasma corticosterone levels the following morning. Repeated treatment with CRH over a 1.5-hour period models some of the behavioral changes observed after exposure to intense inescapable stressors.

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

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. 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. 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. The SC injection of 7-NI and AR-R 17477 significantly enhanced associative learning while ICV administration of SNP significantly retarded learning. 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.

Associative learning changes intrinsic to Hermissenda Type A photoreceptors.

The eyes of the nudibranch mollusc Hermissenda have previously been shown to contain 2 classes of photoreceptors. Type B photoreceptors exhibit increased light responses and membrane excitability after repeated pairings of light and rotation and play an important role in the mediation of associatively produced reductions in phototactic behavior. Type A photoreceptors have also been shown to change with associative training. In previous research, Type A photoreceptors from trained animals were found to have reduced light responses. Because these recordings were obtained from synaptically intact cells, it was not possible to determine whether the effects of associative training reflected changes in synaptic input to Type A photoreceptors or intrinsic changes in somatic conductances. In the present study, intracellular recordings from synaptically isolated Type A photoreceptors were obtained on retention days after training, and pairing-specific decreases in light-induced generator potentials and decreases in resting input resistance were observed. Current- and voltage-clamp analysis of Type A photoreceptors from untrained animals revealed that an important determinant of the steady-state light response was a calcium-activated K+ current (IK-Ca). Thus, Type A photoreceptors also appear to be a primary site for associative information storage in Hermissenda. It is suggested that enhancement of IK-Ca by associative training may contribute to the diminished light response of Type A photoreceptors.

Associative learning changes intrinsic to Hermissenda Type A photoreceptors.

Associative learning changes intrinsic to Hermissenda Type A photoreceptors.

Leg flexion conditioning in the rat: Its advantages and disadvantages as a model system of age-related changes in associative learning

Twelve- and 28-month-old Fischer 344 rats of both sexes received five 60-trial sessions of Pavlovian conditioning in which the CS was a 75 dB, 10,000 Hz tone, and the US was a 0.5-mA, 0.5-sec duration footshock. Right foreleg flexion was measured as the conditioned response (CR). Other animals received a random sequence of unpaired tones and footshock and served as pseudoconditioning control groups. Interstimulus intervals (ISIs) of 1.5 and 3.5 sec were studied. The longer ISI resulted in higher rates of responding in both the conditioning and pseudoconditioning groups. However, with the exception of the young males, all animals showed significantly higher levels of responding in the conditioning groups. Females also showed faster acquisition and higher levels of responding than males. A significant sex by age by sessions interaction occurred, suggesting that old males may be somewhat retarded in acquiring the leg flexion CR compared to the other groups of animals. Old males were also slower to reach a criterion of 5 successive CRs than either young males or young or old females.

Age-related changes in associative learning: Studies in rabbits and rats

Two experimental models for studying age-related changes in associative learning are described. One involves classical (Pavlovian) conditioning of eyeblink and heart rate in the rabbit. The second involves Pavlovian leg flexion and heart rate conditioning in the rat. Advantages and disadvantages of each model are discussed. Results with both models suggest differential effects of aging on acquisition of autonomic and somatomotor responses, thus underlining the utility of assessing multiple response systems to adequately characterize age-related changes in learning and memory.