A mutation in the AMPA-type glutamate receptor, glr-1, blocks olfactory associative and nonassociative learning in Caenorhabditis elegans.

The α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type ionotropic glutamate receptor mediates fast excitatory neurotransmission in the vertebrate brain and is important for synaptic plasticity and the initial induction of long-term potentiation (LTP). This study found that the putative Caenorhabditis elegans AMPA receptor gene, glr-1, plays a significant role in experience-dependent behavior in C. elegans. glr-1 mutants are deficient in an olfactory associative learning task, in which diacetyl (DA) is paired with acetic acid solution. glr-1 mutant nematodes are also impaired in nonassociative learning (habituation) with the same DA stimulus. The C. elegans learning mutants, lrn-1 and lrn-2, are impaired in chemosensory associative learning yet have no deficits in habituation. The results suggest that although associative and nonassociative learning can be genetically dissociated ( lrn-1 and lrn-2), they also share some common molecular processes, including glr-1 -mediated neurotransmission. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mutations that prevent associative learning in C. elegans.

The nematode Caenorhabditis elegans offers a promising system for the reductionist study of learning and memory. In this article, classical conditioning in C. elegans is demonstrated with a variety of associative learning assays. These assays allowed for the isolation and behavioral characterization of 2 mutant C. elegans lines impaired in associative learning. Both lines show no short-term or long-term associative conditioning; however, they appear relatively normal in tests of nonassociative learning and sensorimotor function. In combination with the well-described genetics and neuroanatomy of C. elegans, the isolation of mutants selectively, yet completely, blocked in associative learning provides the basis for an effective characterization of the cellular and molecular aspects of associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context conditioning in habituation in the nematode Caenorhabditis elegans.

Habituation has traditionally been considered a nonassociative form of learning. However, recent research suggests that retention of this nonassociative form of learning may be aided by associations formed during training. An example of this is context conditioning, in which animals that are trained and tested in the presence of a contextual cue show greater retention than animals trained and tested in different environments. This article reports context conditioning in habituation in the nematode Caenorhabditis elegans. The results showed that retention of habituation to tap at both 10- and 60-s interstimulus intervals was significantly greater if training and testing occurred in the presence of the same chemosensory cue (NaCH?COO). This context conditioning showed both extinction and latent inhibition, demonstrating that these simple worms with only 302 neurons are capable of associative context conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Genetic Dissociation of Learning and Recall in Caenorhabditis elegans.

A learning event can be dissociated into 3 components: acquisition, storage, and recall. When the laboratory wild-type strain of Caenorhabditis elegans (N2 strain) is exposed to benzaldehyde in the absence of food, the worms display a reduction of their attractive response to this volatile odorant. This results from the association between benzaldehyde and a nutrient-deficient environment. Another wild-type isolate, the CB4856 strain, fails to display this decreased response to benzaldehyde after exposure to benzaldehyde in the absence of food. However, like the N2 strain, when tested to isoamyl alcohol after benzaldehyde conditioning, the CB4856 strain displays a decreased isoamyl alcohol response. Therefore, the CB4856 strain does not have an acquisition deficit, but it suffers from a recall deficit specific to benzaldehyde. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recovery from habituation in Caenorhabditis elegans is dependent on interstimulus interval and not habituation kinetics.

The habituation of the tap withdrawal reflex of Caenorhabditis elegans was assessed to determine whether the kinetics of recovery from habituation were dependent on the interstimulus interval (ISI) uscd during habituation training or alternately, on the rate and asymptotic level of habituation produced at a given ISI. Two groups of intact animals were trained at either a 10-s (CON10) or a 60-s (CON60) ISI Laser ablation was used to alter the habituation kinetics in one further group of animals (PLM10) independent of ISI. Although the PLM10 animals trained at a 10-s ISI habituated like CON60 worms the recovery from habituation of the PLM10 animals very closely resembled the recovery of the CON10 worms. Thus recovery kinetics are dictated by consequences of a given ISI which do not impact upon habituation rate and asymptote. This suggests the recruitment of multiple ISI-dependent processes during habituation in C. elegans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tap withdrawal circuit interneurons require CREB for long-term habituation in Caenorhabditis elegans.

We investigated the role of the Caenorhabditis elegans CREB (cAMP response element binding protein) homologue, crh-1, in response to tap (nonlocalized mechanosensory stimulation) and tap habituation. Worms with a loss-of-function mutation in crh-1 performed smaller reversals in response to tap than did wild-type worms and did not show long-term memory for spaced training 24-hr posttraining; however, they did show short-term habituation to tap stimuli when stimuli were presented at both 10-s and 60-s interstimulus intervals, and showed 12-hr intermediate memory for spaced habituation training (intermediate-term memory). Expressing CRH-1 broadly throughout the nervous system and in a subset of interneurons of the tap withdrawal circuit, but not in the mechanosensory neurons, rescued the long-term memory defects observed in crh-1 mutants. Here we show for the first time that CREB is required for long-term habituation and show that the interneurons of the tap withdrawal response circuit are the locus of plasticity for long-term mechanosensory habituation in C. elegans. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Conditional associative learning is impaired in cerebellar disease in humans.

Eight patients with lesions restricted to the cerebellum were compared with a total of 25 age-matched controls on an reaction time (RT) task allowing the recording of simple and choice RTs as well as RTs to abstract visual patterns signifying the particular movement to be performed. In all conditions the actual movements required (either a left or a right button press) remained the same, but the cognitive requirements of the task varied. In the abstract patterns condition, the significance of the various patterns with regard to the required movement had to be learned by the Ss. The patients with cerebellar lesions were particularly impaired in this condition. It is concluded that the cerebellum is involved not just in the timing of movements but also in the decision process as to which movement should be performed under particular circumstances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of changing interstimulus interval during habituation in Caenorhabditis elegans..

The role of the interstimulus interval (ISI) in habituation in Caenorhabditis elegans was explored by examining the effect of changing the ISI on habituation and on spontaneous recovery from habituation. When habituation stimuli were delivered at variable ISIs with an average of 10 s, recovery was slower than when habituation stimuli were delivered at fixed 10-s intervals. There were no differences in recovery following either fixed or variable stimulation at a 60-s ISI. The effect of shifting to a different ISI during habituation training was also explored. A 60-s ISI affected habituation at a 10-s ISI, but a 10-s ISI did not influence habituation at a 60-s ISI. Therefore, habituation must be viewed as an ongoing equilibrium of a number of cellular processes—some decrementing, some facilitating—that are differentially activated at different ISIs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Factors affecting habituation and recovery from habituation in the nematode Caenorhabditis elegans..

In 4 experiments, the factors that affect the rate of habituation, the degree of habituation, and the rate of recovery from habituation in a simple reflex circuit in Caenorhabditis elegans were investigated. Results showed that habituation was more pronounced and faster, and that recovery from habituation was more rapid, with short interstimulus intervals (ISIs) rather than with longer ISIs. Rate of recovery differed in animals that had reached asymptotic response levels when compared with animals still in the descending portion of the habituation curve. Once animals reached asymptotic response levels, rate of recovery appeared to be determined by ISI and not by additional stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

ALDH2, ADH1B and alcohol expectancies: Integrating genetic and learning perspectives.

The present study evaluated associations of ALDH2 and ADH1B genotypes with alcohol expectancies and drinking behavior in a sample of Asian American young adults. In addition to assessing global alcohol expectancies, the authors developed a measure of physiological expectancies to evaluate an expectancy phenotype specific to the mechanism by which ALDH2 and ADH1B variations presumably influence drinking behavior. Compared with individuals with the ALDH2*1/*1 genotype, those with the ALDH2*2 allele reported greater negative alcohol expectancies, greater expectancies for physiological effects of alcohol and lower rates of alcohol use. ADH1B was not associated with alcohol expectancies or drinking behavior. Hierarchical models showed that demographic factors, ALDH2 genotype, and expectancy variables explained unique variance in drinking outcomes. Mediation tests showed significant indirect effects of ALDH2 on drinking frequency and peak lifetime consumption through expectancies. These results provide support for influences of genetic factors and alcohol sensitivity on alcohol-related learning and suggest the importance of developing biopsychosocial models of drinking behavior in Asian Americans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of tap withdrawal response habituation on other withdrawal behaviors: The localization of habituation in the nematode Caenorhabditis elegans.

Four experiments were conducted to identify the possible loci of habituation of the nematode tap withdrawal response (TWR) by charactering the effects of TWR habituation on other nonmechanosensory withdrawal behaviors that are mediated by overlapping sets of neurons. Experiments 1–2 established behavioral and anatomical relationships between spontaneous and tap-induced backward locomotion in the worm. Experiment 3 demonstrated that habituation of the TWR affected neither the magnitude nor frequency of spontaneous reversal activity. Experiment 4 extended this result to an evoked response: Habituation of the TWR had no effect on reversals evoked by a thermal stimulus. These studies, which show that the loci of change associated with habituation of the TWR are presynaptic to the interneurons and motor neurons that control locomotion, probably distributed among the mechanosensory neurons, illustrate that a complete understanding of plasticity requires a knowledge of both the anatomical and molecular substrates of change. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Associative learning in the marsupials Didelphis albiventris and Lutreolina crassicaudata..

A procedure to study associative learning in didelphid marsupials (Didelphis albiventris and Lutreolina crassicaudata) was developed, based on the use of an appetitive unconditioned stimulus, discrete conditioned stimuli, and multiple-behavior recordings of freely moving animals. In Experiments 1 and 2, three basic conditioning phenomena were reported: differential conditioning, stimulus reversal, and summation. A specific behavior developed during the excitatory signal, independently of the particular stimulus involved, consisting of rhythmic, goal-centered, sagittal head movements, highly similar across subjects and species. Unlike previous experiments on Pavlovian conditioning in marsupials, the use of differential conditioning in within-subjects designs, with appropriate counterbalance of stimuli, precludes interpretation of these results in terms of pseudoconditioning, sensitization, or sensory-perceptual effects. These results open the possiblity for systematic research on the comparative, developmental, and neuropsychological aspects of learning to which marsupials can contribute as models. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal order sensitivity of associative neural and behavioral changes in Hermissenda..

Hermissenda's neural and behavioral changes produced by light-rotation pairings were assessed as a function of the temporal relations between visual and vestibular stimulation. The results of in vitro simulations of conditioning indicated that simultaneous pairings (synchronous onsets and offsets of light and caudal hair cell stimulation) resulted in significantly greater cumulative depolarization of Type B photoreceptors than did either forward (light preceded hair cell stimulation) or backward (hair cell stimulation preceded light) pairings. Further experiments revealed that the attenuation of cumulative depolarization produced by the forward and backward pairings reflected the asynchrony of stimulus offsets that characterize these conditioning sequences, rather than their onsets. Analogous behavioral experiments revealed that intact animals trained with forward or backward pairings exhibited significantly less conditioning than those trained with simultaneous pairings. Strong parallels between the magnitude of cumulative depolarization from in vitro conditioning studies and the behavioral results for intact animals were also observed in experiments in which stimulus onset synchrony was held constant but offsets were made asynchronous, and vice versa. Thus Hermissenda exhibits a sensitivity to the temporal arrangement of light and rotation, and the results of behavioral conditioning can be predicted accurately from the outcome of in vitro conditioning of the isolated nervous system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Presence of conspecifics facilitates learning that food is inedible in Aplysia fasciata..

Absence of a conspecific, but not of food, interfered with learning and memory of a feeding task in Aplysia fasciata. Interference was shown by a shortened training session and by lack of savings on retraining. The shortened training was not responsible for the lack of savings because brief training in the presence of a conspecific led to savings on retraining. Animals trained in the absence of a conspecific and then tested in its presence did not show signs of having learned, which indicates that the absence of a conspecific interfered with the ability to learn, rather than with the expression of memory. Absence of a conspecific also inhibited other aspects of feeding behavior, such as the latency to respond to food and the length of time that animals respond to food, which indicate that interference with learning was apparently caused by inhibition of feeding behavior, rather than by block of the mechanisms underlying learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A replication demonstrating reduced courtship of Drosophila melanogaster by associative learning.

The study of experience-mediated reductions in the courtship of Drosophila melanogaster has stimulated wide interest because of its apparent importance for reproduction, interaction with chemical communication, and the ability to study individual subjects. This report replicates control procedures developed to account for nonassociative effects. The data indicate that male D. melanogaster associate the responses to inhibitory and excitatory cues provided by a mated female and that subsequent presentation of a virgin female results in lower than expected levels of courtship. This reduction is not a result of habituation or fatigue. I hypothesized that this associative effect results from counterconditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Socially mediated learning in male Betta splendens..

Showed, in 7 experiments, that in the absence of social stimulation male Siamese fighting fish would approach any of several visual and spatial cues that had previously been paired with the Ss' mirror images. Findings demonstrate that learned modifications of swimming mediated by social stimuli are possible in Bettas. Results suggest that Ss learned to exhibit conditioned gill-cover erection as part of a pattern of locomotion that could effectively maintain territories. Nearly all Ss learned to swim in proximity to visual and spatial cues previously presented with conspecific images. Results also suggest that territorial defense in some teleosts may be mediated by the association of social cues with visual and spatial stimuli. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Meta-analyses of ALDH2 and ADH1B with alcohol dependence in Asians.

Meta-analyses were conducted to determine the magnitude of relationships between polymorphisms in 2 genes, ALDH2 and ADH1B, with alcohol dependence in Asians. For each gene, possession of 1 variant *2 allele was protective against alcohol dependence, and possession of a 2nd *2 allele did not offer significant additional protection. The protective effects of these 2 gene polymorphisms were independent. Diagnostic criteria, recruitment strategy, and Japanese ethnicity moderated the effect of ALDH2*2. Recruitment strategy and gender moderated the effect of ADH1B*2. These findings highlight the importance of methodological issues and potential gene-gene and gene-environment interactions that must be considered when examining relationships between genetic polymorphisms and phenotypes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social behavior in Fmr1 knockout mice carrying a human FMR1 transgene.

Fragile X syndrome (FXS) results from the loss of expression of the fragile X mental retardation (FMR1) gene. Individuals affected by FXS experience many behavioral problems, including cognitive impairment, hyperactivity, social anxiety, and autistic-like behaviors. A mouse model of Fmr1 deficiency (Fmr1KO) exhibits several similar behavioral phenotypes, including alterations in social behavior. In an earlier study, Fmr1 knockout mice carrying a yeast-artificial chromosome (YAC) transgene that over-expresses normal human FMRP (KOYAC) showed a correction or overcorrection of some behavioral responses, such as hyperactivity and anxiety-related responses. This report presents results from a study examining transgenic rescue of abnormal social responses in Fmr1KO mice. Relative to their wild-type (WT) littermates, Fmr1KO mice made more active social approaches to standard C57BL/6 partner mice in a direct social interaction test, a result consistent with a previous study. KOYAC mice showed fewer active approaches to partners than the WT or Fmr1KO littermates, indicating correction of this phenotype. This finding expands the number of murine behavioral responses caused by Fmr1 deficiency and corrected by overexpression of human FMRP. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aging and monitoring associative learning: Is monitoring accuracy spared or impaired?

Mixed lists of associatively related and unrelated paired associates were used to study monitoring of associative learning. Older and younger adults produced above-chance levels of relative accuracy, as measured by intraindividual correlations (γ) of judgments of learning (JOLs) with item recall. JOLs were strongly influenced by relatedness, and this effect was greater for older adults. Relative accuracy was higher for unrelated than for related pairs. Correlations of JOLs with item recall for a randomly yoked learner indicated that access to one's own encoding experiences increased relative accuracy. Both age groups manifested a contrast effect (lower JOLs for unrelated items when mixed with related items). Aging appears to spare monitoring of encoding, even though it adversely affects associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory Sensitivity for Aliphatic Esters in Spider Monkeys (Ateles geoffroyi).

Using a conditioning paradigm, the authors investigated the olfactory sensitivity of 3 spider monkeys (Ateles geoffroyi) for a homologous series of aliphatic esters (ethyl acetate to n-octyl acetate) and isomeric forms of some of these substances. With all odorants, the monkeys significantly discriminated concentrations below 1 ppm from the odorless solvent, and in several cases, individual monkeys even demonstrated thresholds below 1 ppb. The results showed spider monkeys to have a high olfactory sensitivity for aliphatic esters, which for the majority of substances matches or even is better than that of species such as the rat, the mouse, or the dog. These findings support the assumption that between-species comparisons of neuroanatomical features are poor predictors of olfactory performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)