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Sample records for novelty locomotor response

  1. Differential housing and novelty response: Protection and risk from locomotor sensitization.

    PubMed

    Garcia, Erik J; Haddon, Tara N; Saucier, Donald A; Cain, Mary E

    2017-03-01

    High novelty seeking increases the risk for drug experimentation and locomotor sensitization. Locomotor sensitization to psychostimulants is thought to reflect neurological adaptations that promote the transition to compulsive drug taking. Rats reared in enrichment (EC) show less locomotor sensitization when compared to rats reared in isolation (IC) or standard conditions (SC). The current research study was designed to test if novelty response contributed locomotor sensitization and more importantly, if the different housing environments could change the novelty response to protect against the development of locomotor sensitization in both adolescence and adulthood. Experiment 1: rats were tested for their response to novelty using the inescapable novelty test (IEN) and pseudorandomly assigned to enriched (EC), isolated (IC), or standard (SC) housing conditions for 30days. After housing, they were tested with IEN. Rats were then administered amphetamine (0.5mg/kg) or saline and locomotor activity was measured followed by a sensitization test 14days later. Experiment 2: rats were tested in the IEN test early adulthood and given five administrations of amphetamine (0.3mg/kg) or saline and then either stayed in or switched housing environments for 30days. Rats were then re-tested in the IEN test in late adulthood and administered five more injections of their respective treatments and tested for locomotor sensitization. Results indicate that IC and SC increased the response to novelty. EC housing decreased locomotor response to amphetamine and saline, and SC housing increased the locomotor response to amphetamine. Mediation results indicated that the late adult novelty response fully mediates the locomotor response to amphetamine and saline, while the early adulthood novelty response did not. Differential housing changes novelty and amphetamine locomotor response. Novelty response is altered into adulthood and provides evidence that enrichment can be used to reduce

  2. Novelty response and 50 kHz ultrasonic vocalizations: Differential prediction of locomotor and affective response to amphetamine in Sprague-Dawley rats

    PubMed Central

    Garcia, Erik J.; Cain, Mary E.

    2015-01-01

    Rationale Novelty and sensation seeking (NSS) predisposes humans and rats to experiment with psychostimulants. In animal models, different tests of NSS predict different phases of drug dependence. Ultrasonic vocalizations (USV) are evoked by psychomotor stimulants and measure the affective/motivation response to stimuli, yet the role NSS has on USV in response to amphetamine is not determined. Objectives Determine if individual differences in NSS and USV can predict locomotor and USV response to amphetamine (0.3, and 1.0 mg/kg) at different exposure lengths. Methods Thirty male rats were tested for their response to novelty (IEN), choice to engage in novelty (NPP), and heterospecific play (H-USV). Rats were administered non-contingent amphetamine or saline for 7 exposures and USV and locomotor activity were measured. After a 14-day rest, rats were administered a challenge dose of amphetamine. Results Regression analyses indicated that amphetamine dose-dependently increased locomotor activity and the NPP test negatively predicted treatment-induced locomotor activity. The H-USV test predicted treatment-induced frequency modulated (FM) USV, but the strength of prediction depended on IEN response. Conclusions Results provide evidence that locomotor activity and FM USV induced by amphetamine represent different behavioral responses. The prediction of amphetamine-induced FM USV by the H-USV screen was changed by the novelty response, indicating that the affective value of amphetamine—measured by FM USV—depends on novelty response. This provides evidence that higher novelty responders may develop a tolerance faster and may escalate intake faster. PMID:26564232

  3. Association between locomotor response to novelty and light reinforcement: Sensory reinforcement as a rodent model of sensation seeking

    PubMed Central

    Gancarz, Amy M.; Robble, Mykel A.; Kausch, Michael A.; Lloyd, David R.; Richards, Jerry B.

    2013-01-01

    Background The human personality trait of sensation seeking (SS) indicates an attraction to novel sensations and experiences, and is associated with greater likelihood of drug abuse. In rodents, locomotor activity in a novel environment (Loco) has been found to predict drug self-administration (SA), and has been hypothesized to be a translational model of human SS. Previously, we reported (Gancarz et al., 2011 [12]) that high responder (HR) animals responded more than low responder (LR) animals to produce a response contingent light onset. The primary goal of this paper was a detailed analysis of the association between Loco and light contingent responding in a large sample of rats (n = 93). Methods Male rats were pre-exposed to dark operant test chambers for ten 30 min sessions and baseline levels of responding (snout poking) were determined. The pre-exposure phase was followed by 6 sessions during which active responding produced a visual sensory reinforcer (VSR; 5 s light onset) according to a variable interval 1 min schedule of reinforcement. After completion of the VSR phase, Loco was tested. Results The activating effects (total responding) of light were associated with Loco, but the response guiding effects (proportion of active responding) of the light were not. In addition, HR rats habituated more slowly in both the VSR and Loco tests than LR rats. Conclusions These data indicate that VSR measures aspects of the rodent’s response to novel sensations and experiences that are not detected by Loco. These data provide some evidence for the use of light reinforcement as an animal model of SS. PMID:22586716

  4. Individual differences in rats' reactivity to novelty and the unconditioned and conditioned locomotor effects of methamphetamine.

    PubMed

    Bevins, Rick A; Peterson, Jessica L

    2004-09-01

    Rat's reactivity to inescapable novelty can predict the subsequent psychomotor effects of many stimulants. This relation has not been examined for methamphetamine. Experiment 1 assessed the locomotor effects of methamphetamine (0.0625-1.0 mg/kg). On average, acute administration of methamphetamine (0.25, 0.5, and 1 mg/kg) had a stimulant effect on activity; locomotor sensitization was seen after repeated administration of 0.5 and 1 mg/kg. In a subsequent drug-free test, rats that had the locomotor chamber paired with 0.25, 0.5, or 1 mg/kg methamphetamine on eight separate occasions were more active than controls--conditioned hyperactivity. Experiment 2 used the 0.5-mg/kg dose to examine whether forced novelty exposure (novelty-induced activity) or free-choice novelty (approach to novel environment or object interaction) was predictive of methamphetamine's psychomotor effects. Only reactivity to inescapable novelty was systematically correlated with methamphetamine-induced activity. Rats more reactive to novelty [high responders (HR)] were more active to the acute and chronic methamphetamine challenge. Furthermore, these HR showed more conditioned hyperactivity than low responders (LR). Although acute methamphetamine did not have a stimulant effect in LR, only the LR displayed locomotor sensitization after chronic methamphetamine. This research extends the predictive variable of reactivity to inescapable novelty to methamphetamine's conditioned and unconditioned locomotor effects.

  5. METHAMPHETAMINE TREATMENT CAUSES DELAYED DECREASE IN NOVELTY-INDUCED LOCOMOTOR ACTIVITY IN MICE

    PubMed Central

    Krasnova, Irina N.; Hodges, Amber B.; Ladenheim, Bruce; Rhoades, Raina; Phillip, Crystal G.; Ceseňa, Angela; Ivanova, Ekaterina; Hohmann, Christine F.; Cadet, Jean Lud

    2009-01-01

    Methamphetamine (METH) is a psychostimulant that causes damage to dopamine (DA) axons and to non-monoaminergic neurons in the brain. The aim of the present study was to investigate short- and long-term effects of neurotoxic METH treatment on novelty-induced locomotor activity in mice. Male BALB/c mice, 12–14 weeks old, were injected with saline or METH (i.p., 7.5 mg/kg × 4 times, every 2 hours). Behavior and neurotoxic effects were assessed at 10 days, 3 and 5 months following drug treatment. METH administration caused marked decreases in DA levels in the mouse striatum and cortex at 10 days post-drug. However, METH did not induce any changes in novelty-induced locomotor activity. At 3 and 5 months after treatment METH-exposed mice showed significant recovery of DA levels in the striatum and cortex. In contrast, these animals demonstrated significant decreases in locomotor activity at 5 months in comparison to aged-matched control mice. Further assessment of METH toxicity using TUNEL staining showed that the drug induced increased cell death in the striatum and cortex at 3 days after administration. Taken together, these data suggest that delayed deficits in novelty-induced locomotor activity observed in METH exposed animals are not due to neurodegeneration of DA terminals but to combined effects of METH and age-dependent dysfunction of non-DA intrinsic striatal and/or corticostriatal neurons. PMID:19559060

  6. Sex differences in the effects of social and physical environment on novelty-induced exploratory behavior and cocaine-stimulated locomotor activity in adolescent rats.

    PubMed

    Zakharova, Elena; Starosciak, Amy; Wade, Dean; Izenwasser, Sari

    2012-04-21

    Many factors influence the rewarding effects of drugs such as cocaine. The present study was done to determine whether social and environmental factors alter behavior in adolescent male and female rats. On postnatal day (PND) 23, rats were housed in one of several same-sex conditions. Both social (number of rats per cage) and environmental (availability of toys) factors were manipulated. Socially isolated rats were housed alone (1 rat/cage) in an environment that either was impoverished (with no toys; II) or enriched (with toys; IE). Standard housing for these studies was social and impoverished, which was 2 rats/cage with no toys (SI2). Other rats were housed 2/cage with toys (SE2), or 3/cage with (SE3) or without (SI3) toys. On PND 37, novelty-induced locomotor activity was measured for 30min. On PND 44-46, locomotor activity in response to an injection of 5mg/kg cocaine was measured for 60min each day. For male rats, only social conditions altered novelty-induced activity. Males housed in groups of three had the most activity, compared to pair-housed and isolated rats. For females, social and environmental enrichment interacted to alter novelty-induced activity. In contrast to males, isolated females had increased activity, compared to group-housed females. Further, isolated females in impoverished environments had more activity than isolated females in enriched environments and group-housed females in impoverished environments. The effect of environmental enrichment on cocaine-stimulated locomotor activity was altered depending upon the number of rats living in a cage for males. For females, only social conditions altered cocaine-stimulated behavior, with activity increasing with the number of rats in the cage, regardless of environmental enrichment. These data show that social and environmental enrichment differentially alter novelty-induced and cocaine-stimulated locomotor activity in adolescent male and female rats.

  7. Dexamethasone suppresses the locomotor response of neonatal rats to novel environment.

    PubMed

    Menshanov, Petr N; Bannova, Anita V; Dygalo, Nikolay N

    2014-09-01

    Locomotion of animals in the novel environment is determined by two main factors-the intrinsic motor activity and the specific locomotor response to novelty. Glucocorticoids alter neurobehavioral development of mammals and its locomotor manifestations. However, it remains unclear whether the intrinsic and/or the novelty-induced activity are affected by glucocorticoids during early life. Here, the principal component analysis was used to determine the main factors that underlie alterations in locomotion of rat pups treated with dexamethasone. It was shown that neonatal rats exhibited an enhanced locomotion in the novel environment beginning from postnatal day (PD) 5. We found for the first time that this reaction was significantly suppressed by dexamethasone. The effect was specific to the novelty-induced component of behavior, while the intrinsic locomotor activity was not affected by glucocorticoid treatment. The suppression of the behavioral response to novelty was maximal at PD7 and vanquished at PD10-11. In parallel with the hormonal effect on the behavior, dexamethasone upregulated the main cell death executor-active caspase-3 in the prefrontal cortex of 7-day old rats. Thus, dexamethasone-induced alterations in the novelty-related behavior may be the earliest visible signs of the brain damage that could lead to forthcoming depressive state or schizophrenia, emerging as a result of neonatal stress or glucocorticoid treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Statistical Analysis of Zebrafish Locomotor Response

    PubMed Central

    Zhang, Gaonan; Venkatraman, Prahatha; Brown, Skye Ashton; Pang, Chi-Pui; Zhang, Mingzhi; Ma, Ping; Leung, Yuk Fai

    2015-01-01

    Zebrafish larvae display rich locomotor behaviour upon external stimulation. The movement can be simultaneously tracked from many larvae arranged in multi-well plates. The resulting time-series locomotor data have been used to reveal new insights into neurobiology and pharmacology. However, the data are of large scale, and the corresponding locomotor behavior is affected by multiple factors. These issues pose a statistical challenge for comparing larval activities. To address this gap, this study has analyzed a visually-driven locomotor behaviour named the visual motor response (VMR) by the Hotelling’s T-squared test. This test is congruent with comparing locomotor profiles from a time period. Different wild-type (WT) strains were compared using the test, which shows that they responded differently to light change at different developmental stages. The performance of this test was evaluated by a power analysis, which shows that the test was sensitive for detecting differences between experimental groups with sample numbers that were commonly used in various studies. In addition, this study investigated the effects of various factors that might affect the VMR by multivariate analysis of variance (MANOVA). The results indicate that the larval activity was generally affected by stage, light stimulus, their interaction, and location in the plate. Nonetheless, different factors affected larval activity differently over time, as indicated by a dynamical analysis of the activity at each second. Intriguingly, this analysis also shows that biological and technical repeats had negligible effect on larval activity. This finding is consistent with that from the Hotelling’s T-squared test, and suggests that experimental repeats can be combined to enhance statistical power. Together, these investigations have established a statistical framework for analyzing VMR data, a framework that should be generally applicable to other locomotor data with similar structure. PMID

  9. Individual differences in novelty-seeking and behavioral responses to nicotine: a review of animal studies.

    PubMed

    Redolat, Rosa; Pérez-Martínez, Asunción; Carrasco, M Carmen; Mesa, Patricia

    2009-09-01

    Individual differences in the behavioral responses to a novel environment have been proposed as a research tool to predict responsiveness to other behavioral tasks, response to certain events and individual vulnerability to nicotine addiction. In rats and mice, novelty seeking (defined as enhanced specific exploration of novel situations) is a complex behavior confirmed by a large body of neurochemical, endocrinological and behavioral data. We review the main standardized procedures employed to measure the novelty seeking trait in rodents and the ontogeny of this behavior throughout the life-span taking into account that novelty seeking can be permanently modified as a consequence of particular early experiences, maternal care, and environmental enrichment. Studies in animal models suggest that individual differences in the sensitivity to nicotine depend on different variables such as basal locomotor activity of the experimental subjects, their response to novel environments (open-field, hole-board) and level of impulsivity. It is concluded that these basic findings contribute to a better understanding of smoking behavior and to the establishment of improved pharmacological treatments if individual differences are borne in mind.

  10. Picture Novelty Influences Response Selection and Inhibition: The Role of the In-Group Bias and Task-Difficulty

    PubMed Central

    Zinchenko, Artyom; Mahmud, Waich; Alam, Musrura Mefta; Kabir, Nadia; Al-Amin, Md. Mamun

    2016-01-01

    The human visual system prioritizes processing of novel information, leading to faster detection of novel stimuli. Novelty facilitates conflict resolution through the enhanced early perceptual processing. However, the role of novel information processing during the conflict-related response selection and inhibition remains unclear. Here, we used a face-gender classification version of the Simon task and manipulated task-difficulty and novelty of task-relevant information. The novel quality of stimuli was made task-irrelevant, and an in-group bias was tightly controlled by manipulation of a gender of picture stimuli. We found that the in-group bias modulated the role of novelty in executive control. Novel opposite-sex stimuli facilitated response inhibition only when the task was not demanding. By contrast, novelty enhanced response selection irrespective of the in-group factor when task-difficulty was increased. These findings support the in-group bias mechanism of visual processing, in cases when attentional resources are not limited by a demanding task. The results are further discussed along the lines of the attentional load theory and neural mechanisms of response-inhibition and locomotor activity. In conclusion, our data showed that processing of novel information may enhance executive control through facilitated response selection and inhibition. PMID:27788213

  11. Contrasting responses to novelty by wild and captive orangutans.

    PubMed

    Forss, Sofia I F; Schuppli, Caroline; Haiden, Dominique; Zweifel, Nicole; van Schaik, Carel P

    2015-10-01

    Several studies have suggested that wild primates tend to behave with caution toward novelty, whereas captive primates are thought to be less neophobic, more exploratory, and more innovative. However, few studies have systematically compared captive and wild individuals of the same species to document this "captivity effect" in greater detail. Here we report the responses of both wild and captive orangutans to the same novel items. Novel objects were presented to wild orangutans on multiple platforms placed in the canopy and equipped with motion-triggered video cameras. The same and different novel objects were also presented to orangutans in two different zoos. The results demonstrate extreme conservatism in both Bornean and Sumatran wild orangutans, who gradually approached the novel objects more closely as they became familiar, but avoided contact with them over many encounters spanning several months. Their zoo-living conspecifics, in contrast, showed an immediate neophilic response. Our results thus confirm the "captivity effect." To the various ecological explanations proposed before (reduced risk and increased time and energy balance for captive individuals relative to wild ones), we add the social information hypothesis, which claims that individuals confronted with novel items preferentially rely on social cues whenever possible. This caution toward novelty disappears when human caretakers become additional role models and can also be eroded when all experience with novelty is positive.

  12. High locomotor reactivity to novelty is associated with an increased propensity to choose saccharin over cocaine: new insights into the vulnerability to addiction.

    PubMed

    Vanhille, Nathalie; Belin-Rauscent, Aude; Mar, Adam C; Ducret, Eric; Belin, David

    2015-02-01

    Drug addiction is associated with a relative devaluation of natural or socially-valued reinforcers that are unable to divert addicts from seeking and consuming the drug. Before protracted drug exposure, most rats prefer natural rewards, such as saccharin, over cocaine. However, a subpopulation of animals prefer cocaine over natural rewards and are thought to be vulnerable to addiction. Specific behavioral traits have been associated with different dimensions of drug addiction. For example, anxiety predicts loss of control over drug intake whereas sensation seeking and sign-tracking are markers of a greater sensitivity to the rewarding properties of the drug. However, how these behavioral traits predict the disinterest for natural reinforcers remains unknown. In a population of rats, we identified sensation seekers (HR) on the basis of elevated novelty-induced locomotor reactivity, high anxious rats (HA) based on the propensity to avoid open arms in an elevated-plus maze and sign-trackers (ST) that are prone to approach, and interaction with, reward-associated stimuli. Rats were then tested on their preference for saccharin over cocaine in a discrete-trial choice procedure. We show that HR rats display a greater preference for saccharin over cocaine compared with ST and HA whereas the motivation for the drug was comparable between the three groups. The present data suggest that high locomotor reactivity to novelty, or sensation seeking, by predisposing to an increased choice toward non-drug rewards at early stages of drug use history, may prevent the establishment of chronic cocaine use.

  13. Functional brain asymmetry in adult novelty response: on fluidity of neonatal novelty exposure effects.

    PubMed

    Tang, Akaysha C; Reeb-Sutherland, Bethany; Yang, Zhen

    2011-08-01

    Novelty and surprises differentially modify the left and right sides of the brain. Here we show that repeated brief exposures to the novelty of a non-home environment during infancy and early adulthood lead to long-lasting changes in adulthood in the global bi-lateralization organization of the brain as indexed by a transiently detectable right-sided orientating bias upon the initial encounter with the novel environment. Most surprisingly, we show that in the same individuals, the short-term effect of the combined neonatal and adulthood novelty exposures on functional brain asymmetry measured at young adulthood (5 months of age) is distinctively different from the long-term effect measured at late adulthood (15 months of age). These results suggest that long-lasting, cumulative effects of early life experience on brain and behavior organization are not necessarily permanent, but continue to unfold, presumably via interactions with a multitude of unmonitored intervening life events.

  14. High Locomotor Reactivity to Novelty Is Associated with an Increased Propensity to Choose Saccharin Over Cocaine: New Insights into the Vulnerability to Addiction

    PubMed Central

    Vanhille, Nathalie; Belin-Rauscent, Aude; Mar, Adam C; Ducret, Eric; Belin, David

    2015-01-01

    Drug addiction is associated with a relative devaluation of natural or socially-valued reinforcers that are unable to divert addicts from seeking and consuming the drug. Before protracted drug exposure, most rats prefer natural rewards, such as saccharin, over cocaine. However, a subpopulation of animals prefer cocaine over natural rewards and are thought to be vulnerable to addiction. Specific behavioral traits have been associated with different dimensions of drug addiction. For example, anxiety predicts loss of control over drug intake whereas sensation seeking and sign-tracking are markers of a greater sensitivity to the rewarding properties of the drug. However, how these behavioral traits predict the disinterest for natural reinforcers remains unknown. In a population of rats, we identified sensation seekers (HR) on the basis of elevated novelty-induced locomotor reactivity, high anxious rats (HA) based on the propensity to avoid open arms in an elevated-plus maze and sign-trackers (ST) that are prone to approach, and interaction with, reward-associated stimuli. Rats were then tested on their preference for saccharin over cocaine in a discrete-trial choice procedure. We show that HR rats display a greater preference for saccharin over cocaine compared with ST and HA whereas the motivation for the drug was comparable between the three groups. The present data suggest that high locomotor reactivity to novelty, or sensation seeking, by predisposing to an increased choice toward non-drug rewards at early stages of drug use history, may prevent the establishment of chronic cocaine use. PMID:25120076

  15. Zebrafish Locomotor Responses Predict Irritant Potential of ...

    EPA Pesticide Factsheets

    Over the past few decades, the drying and warming trends of global climate change have increased wildland fire (WF) season length, as well as geographic area impacted. Consequently, exposures to WF fine particulate matter (PM2.5; aerodynamic diameter <2.5 µm) are likely to increase in frequency and duration, contributing to a growing public health burden. Given the influence of fuel type and combustion conditions on WFPM2.5 composition, there is pressing need to identify the biomass fuel sources and emission constituents that drive toxicity. Previously, we reported the utility of 6-day post-fertilization (dpf) zebrafish larvae in evaluating diesel exhaust PM-induced irritation, demonstrating responses analogous to those in mammals. In the present study, combustions, separated by smoldering or flaming conditions, of pine needles, red oak, pine, eucalyptus, and peat were achieved using an automated tube furnace paired with a cryo-trapping apparatus to collect condensates of emissions. The condensates were extracted and prepared for use in zebrafish assays. We hypothesized that 1) the extractable organic fractions of biomass smoke PM will elicit dose-dependent irritant responses in 6-dpf zebrafish larvae, and 2) the relative potencies will vary across biomass emissions, potentially driven by varying chemical composition of fuel sources. Six-dpf zebrafish (n= 28-32/group) were exposed acutely to PM extracts (5 concentrations; 0.3-30 µg/ml; half-log intervals) and

  16. Effects of Risperidone and Paliperidone Pretreatment on Locomotor Response Following Prenatal Immune Activation

    PubMed Central

    Richtand, Neil M.; Ahlbrand, Rebecca; Horn, Paul; Stanford, Kevin; Bronson, Stefanie L.; McNamara, Robert K.

    2011-01-01

    Aim Limited data are available regarding pharmacological characteristics of effective interventions for psychosis prevention. Enrollment challenges in psychosis prevention trials impede screening diverse interventions for efficacy. Relevant animal models could help circumvent this barrier. We previously described prevention with risperidone of abnormal behavior following neonatal hippocampal lesion. We aimed to extend those findings evaluating risperidone and paliperidone following prenatal immune activation, a developmental model of a schizophrenia risk factor. We evaluated a later developmental time point to determine persistent effects of drug treatment. Methods Pregnant Sprague-Dawley rats were injected with poly I:C or saline on gestational day 14. Offspring of poly I:C and saline treated dams received risperidone (0.45 mg/kg/d), paliperidone (0.05 mg/kg/d), or vehicle from postnatal days 35 to 70. Locomotor responses to novelty, saline injection, and amphetamine (1 and 5 mg/kg) were determined at three months, i.e., 21 days following antipsychotic discontinuation. Results Risperidone and paliperidone had persistent effects on behavioral response to amphetamine (1 mg/kg) at 3 months, ameliorating the impact of prenatal immune activation on offspring of poly I:C-treated dams. Risperidone, but not paliperidone, also exerted persistent effects in offspring of saline-treated dams on locomotor response to saline and amphetamine (5 mg/kg) injection. Conclusions Risperidone and paliperidone pretreatment of poly I:C offspring during peri-pubertal development stabilized response to amphetamine exposure persisting into early adulthood. Prenatal immune activation provides a model for evaluating effects of an environmental risk factor for schizophrenia, and has potential utility for identifying pharmacological approaches to early intervention. PMID:21440257

  17. Predisposition to self-administer amphetamine: the contribution of response to novelty and prior exposure to the drug.

    PubMed

    Pierre, P J; Vezina, P

    1997-02-01

    The present experiment examined the contribution of locomotor response to novelty and prior exposure to amphetamine to rats' predisposition to self-administer a low dose of the drug. Rats were screened for their locomotor response to a novel environment and divided into high (HR) or low (LR) responders based on whether their locomotor scores were above or below the median activity level of the subject sample. Animals were then pre-exposed to nine daily injections of either saline (1 ml/kg, i.p.) or amphetamine (1.5 mg/kg, i.p.). Starting 1 week after pre-exposure, animals in the four different groups (HR pre-exposed to saline or amphetamine; LR pre-exposed to saline or amphetamine) were given the opportunity, in each of ten daily sessions, to lever press for a low dose of amphetamine (10 micrograms/kg per infusion) in a two lever (active versus inactive) continuous reinforcement operant task. Initial lever press performance revealed no difference in active versus inactive lever pressing between amphetamine and saline pre-exposed animals. However, in agreement with previous reports, with successive test sessions amphetamine pre-exposed rats maintained higher levels of active versus inactive lever pressing for drug while saline pre-exposed rats showed a progressive decrease in the pressing of either lever. Interestingly, this enhanced active lever pressing was observed in HR but not LR rats pre-exposed to amphetamine. In addition, HR saline pre-exposed animals showed initial active versus inactive lever pressing equivalent to that of HR amphetamine pretreated rats but this enhanced responding for drug diminished over days and by the last day of self-administration was indistinguishable from that of LR animals having been pre-exposed either to amphetamine or saline. These findings confirm that prior exposure to amphetamine promotes the subsequent self-administration of the drug and suggest that response to novelty may be a predictor more closely linked to an animal

  18. Dual routes to cortical orienting responses: novelty detection and uncertainty reduction.

    PubMed

    Lange, Florian; Seer, Caroline; Finke, Mareike; Dengler, Reinhard; Kopp, Bruno

    2015-02-01

    Sokolov distinguished between reactive and proactive variants of the orienting response (OR). The Novelty P3 is considered as an electrophysiological signature of the reactive OR. Recent work suggests that the proactive OR is reflected in frontally distributed P3 activity elicited by uncertainty-reducing stimuli in task-switching paradigms. Here, we directly compare the electrophysiological signatures of reactive and proactive ORs. Participants completed a novelty oddball task and a task-switching procedure while the electroencephalogram was measured. Novel and uncertainty-reducing stimuli evoked prominent fronto-centrally distributed Novelty P3 and Uncertainty P3 waves, respectively. We found a substantial negative correlation between Novelty P3 and Uncertainty P3 across participants, suggesting that reactive and proactive ORs converge on a common neural pathway, but also that distinguishable routes to orienting exist. Moreover, response accuracy was associated with reduced Novelty-P3 and enhanced Uncertainty-P3 amplitudes. The relation between Novelty P3 and Uncertainty P3 might serve as an index of individual differences in distractibility and cognitive control.

  19. Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents

    PubMed Central

    Büchel, Christian; Peters, Jan; Banaschewski, Tobias; Bokde, Arun L. W.; Bromberg, Uli; Conrod, Patricia J.; Flor, Herta; Papadopoulos, Dimitri; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Walter, Henrik; Ittermann, Bernd; Mann, Karl; Martinot, Jean-Luc; Paillère-Martinot, Marie-Laure; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Poustka, Luise; Rietschel, Marcella; Robbins, Trevor W.; Smolka, Michael N.; Gallinat, Juergen; Schumann, Gunter; Knutson, Brian; Arroyo, Mercedes; Artiges, Eric; Aydin, Semiha; Bach, Christine; Barbot, Alexis; Barker, Gareth; Bruehl, Ruediger; Cattrell, Anna; Constant, Patrick; Crombag, Hans; Czech, Katharina; Dalley, Jeffrey; Decideur, Benjamin; Desrivieres, Sylvane; Fadai, Tahmine; Fauth-Buhler, Mira; Feng, Jianfeng; Filippi, Irinia; Frouin, Vincent; Fuchs, Birgit; Gemmeke, Isabel; Genauck, Alexander; Hanratty, Eanna; Heinrichs, Bert; Heym, Nadja; Hubner, Thomas; Ihlenfeld, Albrecht; Ing, Alex; Ireland, James; Jia, Tianye; Jones, Jennifer; Jurk, Sarah; Kaviani, Mehri; Klaassen, Arno; Kruschwitz, Johann; Lalanne, Christophe; Lanzerath, Dirk; Lathrop, Mark; Lawrence, Claire; Lemaitre, Hervé; Macare, Christine; Mallik, Catherine; Mar, Adam; Martinez-Medina, Lourdes; Mennigen, Eva; de Carvahlo, Fabiana Mesquita; Mignon, Xavier; Millenet, Sabina; Miranda, Ruben; Müller, Kathrin; Nymberg, Charlotte; Parchetka, Caroline; Pena-Oliver, Yolanda; Pentilla, Jani; Poline, Jean-Baptiste; Quinlan, Erin Burke; Rapp, Michael; Ripke, Stephan; Ripley, Tamzin; Robert, Gabriel; Rogers, John; Romanowski, Alexander; Ruggeri, Barbara; Schmäl, Christine; Schmidt, Dirk; Schneider, Sophia; Schubert, Florian; Schwartz, Yannick; Sommer, Wolfgang; Spanagel, Rainer; Speiser, Claudia; Spranger, Tade; Stedman, Alicia; Stephens, Dai; Strache, Nicole; Ströhle, Andreas; Struve, Maren; Subramaniam, Naresh; Theobald, David; Vetter, Nora; Vulser, Helene; Weiss, Katharina; Whelan, Robert; Williams, Steve; Xu, Bing; Yacubian, Juliana; Yu, Tao; Ziesch, Veronika

    2017-01-01

    Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use. PMID:28221370

  20. Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents.

    PubMed

    Büchel, Christian; Peters, Jan; Banaschewski, Tobias; Bokde, Arun L W; Bromberg, Uli; Conrod, Patricia J; Flor, Herta; Papadopoulos, Dimitri; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Walter, Henrik; Ittermann, Bernd; Mann, Karl; Martinot, Jean-Luc; Paillère-Martinot, Marie-Laure; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Poustka, Luise; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Gallinat, Juergen; Schumann, Gunter; Knutson, Brian

    2017-02-21

    Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use.

  1. Happier, faster: Developmental changes in the effects of mood and novelty on responses.

    PubMed

    Schomaker, Judith; Rangel-Gomez, Mauricio; Meeter, Martijn

    2016-01-01

    Positive mood ameliorates several cognitive processes: It can enhance cognitive control, increase flexibility, and promote variety seeking in decision making. These effects of positive mood have been suggested to depend on frontostriatal dopamine, which is also associated with the detection of novelty. This suggests that positive mood could also affect novelty detection. In the present study, children and adults saw either a happy or a neutral movie to induce a positive or neutral mood. After that, they were shown novel and familiar images. On some trials a beep was presented over headphones either at the same time as the image or at a 200-ms stimulus onset asynchrony (SOA), and the task of the participant was to detect these auditory targets. Children were slower in responding than adults. Positive mood, however, speeded responses, especially in children, and induced facilitatory effects of novelty. These effects were consistent with increased arousal. Although effects of novelty were more consistent with an attentional response, in children who had watched a happy movie the novel images evoked a more liberal response criterion, suggestive of increased arousal. This suggests that mood and novelty may affect response behaviour stronger in children than in adults.

  2. The role of oxytocin in familiarization-habituation responses to social novelty

    PubMed Central

    Tops, Mattie; Huffmeijer, Renske; Linting, Mariëlle; Grewen, Karen M.; Light, Kathleen C.; Koole, Sander L.; Bakermans-Kranenburg, Marian J.; van IJzendoorn, Marinus H.

    2013-01-01

    Stress or arousal responses to novel social contexts ease off when individuals get familiar with the social context. In the present study we investigated whether oxytocin is involved in this process of familiarization-habituation as oxytocin is known to increase trust and decrease anxiety. Fifty-nine healthy female subjects took part in the same experimental procedure in two sessions separated by 4 weeks. In the first (novelty) session state trust scores were significantly positively correlated with salivary oxytocin levels while in the second (familiarity) session state trust scores were significantly negatively correlated with salivary oxytocin levels. In a path model oxytocin was associated with increased trust in the novelty session and trust was associated with decreased oxytocin levels in the familiarity session. The results are consistent with the idea that oxytocin decreases stress-to-novelty responses by promoting familiarization to novel social contexts. PMID:24151482

  3. Repeated amphetamine administration in rats revealed consistency across days and a complete dissociation between locomotor and hypothalamic-pituitary-adrenal axis effects of the drug.

    PubMed

    Gagliano, Humberto; Andero, Raül; Armario, Antonio; Nadal, Roser

    2009-12-01

    Most drugs of abuse stimulate both locomotor activity and the hypothalamic-pituitary-adrenal (HPA) axis, but the relationship between the two responses within the same subjects and their reliabilities has been scarcely studied. Our objectives were to study: (1) the consistency and stability across time of locomotor and HPA activation induced by repeated d-amphetamine (AMPH); (2) the relationship between locomotor and hormonal responses to AMPH; and (3) the relationship between novelty-induced activity and both types of responses to the drug. Male adult rats were exposed to a novel environment to study the locomotor response. Later, they were injected with AMPH (2 mg/kg, sc) for 5 days. In Experiment 1, Plasma adrenocorticotropin (ACTH) and corticosterone levels in response to AMPH were studied on days 1, 3, and 5, and locomotor response on days 2 and 4. In Experiment 2, ACTH and corticosterone responses were studied on days 2 and 4, and locomotor response on days 1, 3, and 5. Across days, both locomotor and HPA responses to the drug were consistent, but independent measures, unrelated to the reactivity to novelty. As measured by the area under the curve, the HPA response to AMPH desensitized with the repeated injection, whereas the initial locomotor response to the drug increased. Dissociation exists between HPA and locomotor activation induced by AMPH, which seemed to be both reliable individual traits. Locomotor reactivity to novelty was related neither to HPA nor to locomotor responses to AMPH.

  4. Making Sense of Infant Familiarity and Novelty Responses to Words at Lexical Onset

    PubMed Central

    DePaolis, Rory A.; Keren-Portnoy, Tamar; Vihman, Marilyn

    2016-01-01

    This study suggests that familiarity and novelty preferences in infant experimental tasks can in some instances be interpreted together as a single indicator of language advance. We provide evidence to support this idea based on our use of the auditory headturn preference paradigm to record responses to words likely to be either familiar or unfamiliar to infants. Fifty-nine 10-month-old infants were tested. The task elicited mixed preferences: familiarity (longer average looks to the words likely to be familiar to the infants), novelty (longer average looks to the words likely to be unfamiliar) and no-preference (similar-length of looks to both type of words). The infants who exhibited either a familiarity or a novelty response were more advanced on independent indices of phonetic advance than the infants who showed no preference. In addition, infants exhibiting novelty responses were more lexically advanced than either the infants who exhibited familiarity or those who showed no-preference. The results provide partial support for Hunter and Ames’ (1988) developmental model of attention in infancy and suggest caution when interpreting studies indexed to chronological age. PMID:27242624

  5. Voluntary ethanol consumption changes anticipatory ultrasonic vocalizations but not novelty response.

    PubMed

    Garcia, Erik J; Jorgensen, Emily T; Sprick, Lukas S; Cain, Mary E

    2017-03-01

    Novelty and sensation seeking (NSS) and affective disorders are correlated with earlier ethanol (ETOH) consumption, and sustained drinking into adulthood. Understanding the NSS response and affective response before and after voluntary ETOH consumption could elucidate important individual differences promoting sustained ETOH consumption. This study determined that NSS and affective response to rewarding stimulation-measured by ultrasonic vocalizations (USVs)-change after adolescent ETOH voluntary drinking. Rats were tested for their NSS response using the inescapable novelty test. Then rats were tested for their affective response to a natural reward and USVs were measured. The natural reward was experimenter-induced play behavior. Rats were exposed to ETOH for 8 weeks using an intermittent two bottle paradigm. After 8 weeks of voluntary consumption, rats were retested for their response to NSS and affective response to natural reward. Results indicate that voluntary ETOH consumption did not change the response to novelty. Control and ETOH exposed rats decreased their novelty response equally after ETOH consumption, suggesting the decrease was due to age. Importantly, voluntary ETOH consumption changed affective USVs. Compared to water-drinking control rats, ETOH-consuming rats elicited greater anticipatory trill USVs to a natural reward-associated context during a post-drinking probe test. Tickle-induced trill USVs did not change differently between ETOH and control rats. These results provide evidence that voluntary intermittent ETOH exposure increases the anticipation of reward and may represent a form of incentive salience. We postulate these diverging effects could be due to differences in incentive salience or reward processing. Together, these results suggest that voluntary ETOH consumption changes the affective response to conditioned and unconditioned natural rewards and offers a behavioral mechanism for studying affective reward processing after ETOH

  6. Finding and Not Finding Rat Perirhinal Neuronal Responses to Novelty

    PubMed Central

    Muller, Robert U.; Brown, Malcolm W.

    2016-01-01

    ABSTRACT There is much evidence that the perirhinal cortex of both rats and monkeys is important for judging the relative familiarity of visual stimuli. In monkeys many studies have found that a proportion of perirhinal neurons respond more to novel than familiar stimuli. There are fewer studies of perirhinal neuronal responses in rats, and those studies based on exploration of objects, have raised into question the encoding of stimulus familiarity by rat perirhinal neurons. For this reason, recordings of single neuronal activity were made from the perirhinal cortex of rats so as to compare responsiveness to novel and familiar stimuli in two different behavioral situations. The first situation was based upon that used in “paired viewing” experiments that have established rat perirhinal differences in immediate early gene expression for novel and familiar visual stimuli displayed on computer monitors. The second situation was similar to that used in the spontaneous object recognition test that has been widely used to establish the involvement of rat perirhinal cortex in familiarity discrimination. In the first condition 30 (25%) of 120 perirhinal neurons were visually responsive; of these responsive neurons 19 (63%) responded significantly differently to novel and familiar stimuli. In the second condition eight (53%) of 15 perirhinal neurons changed activity significantly in the vicinity of objects (had “object fields”); however, for none (0%) of these was there a significant activity change related to the familiarity of an object, an incidence significantly lower than for the first condition. Possible reasons for the difference are discussed. It is argued that the failure to find recognition‐related neuronal responses while exploring objects is related to its detectability by the measures used, rather than the absence of all such signals in perirhinal cortex. Indeed, as shown by the results, such signals are found when a different methodology is used.

  7. Information theory, novelty and hippocampal responses: unpredicted or unpredictable?

    PubMed

    Strange, Bryan A; Duggins, Andrew; Penny, William; Dolan, Raymond J; Friston, Karl J

    2005-04-01

    Shannon's information theory provides a principled framework for the quantitative analysis of brain responses during the encoding and representation of event streams. In particular, entropy measures the expected uncertainty of events in a given context. This contextual uncertainty or unpredictability may, itself, be important for balancing [bottom-up] sensory information and [top-down] prior expectations during perceptual synthesis. Using event-related functional magnetic resonance imaging (fMRI), we found that the anterior hippocampus is sensitive to the entropy of a visual stimulus stream. In contrast, activity in an extensive bilateral cortico-thalamic network was dictated by the surprise or information associated with each particular stimulus. In short, we show that the probabilistic structure or context in which events occur is an important predictor of hippocampal activity.

  8. Neurochemical factors underlying individual differences in locomotor activity and anxiety-like behavioral responses in zebrafish.

    PubMed

    Tran, Steven; Nowicki, Magda; Muraleetharan, Arrujyan; Chatterjee, Diptendu; Gerlai, Robert

    2016-02-04

    Variation among individuals may arise for several reasons, and may have diverse underlying mechanisms. Individual differences have been studied in a variety of species, but recently a new model organism has emerged in this field that offers both sophistication in phenotypical characterization and powerful mechanistic analysis. Recently, zebrafish, one of the favorites of geneticists, have been shown to exhibit consistent individual differences in baseline locomotor activity. In the current study, we further explore this finding and examine whether individual differences in locomotor activity correlate with anxiety-like behavioral measures and with levels of dopamine, serotonin and the metabolites of these neurotransmitters. In addition, we examine whether individual differences in locomotor activity are also associated with reactivity to the locomotor stimulant effects of and neurochemical responses to acute ethanol exposure (30min long, 1% v/v ethanol bath application). Principal component analyses revealed a strong association among anxiety-like responses, locomotor activity, serotonin and dopamine levels. Furthermore, ethanol exposure was found to abolish the locomotion-dependent anxiety-like behavioral and serotonergic responses suggesting that this drug also engages a common underlying pathway. Overall, our results provide support for an important role of the serotonergic system in mediating individual differences in anxiety-like responses and locomotor activity in zebrafish and for a minor modulatory role of the dopaminergic system. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Sex differences in the acute locomotor response to methamphetamine in BALB/c mice.

    PubMed

    Ohia-Nwoko, Odochi; Haile, Colin N; Kosten, Therese A

    2017-06-01

    Women use methamphetamine more frequently than men and are more vulnerable to its negative psychological effects. Rodent models have been an essential tool for evaluating the sex-dependent effects of psychostimulants; however, evidence of sex differences in the behavioral responses to methamphetamine in mice is lacking. In the present study, we investigated acute methamphetamine-induced (1mg/kg and 4mg/kg) locomotor activation in female and male BALB/c mice. We also evaluated whether basal locomotor activity was associated with the methamphetamine-induced locomotor response. The results indicated that female BALB/c mice displayed enhanced methamphetamine-induced locomotor activity compared to males, while basal locomotor activity was positively correlated with methamphetamine-induced activity in males, but not females. This study is the first to show sex-dependent locomotor effects of methamphetamine in BALB/c mice. Our observations emphasize the importance of considering sex when assessing behavioral responses to methamphetamine. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. The pupillary response discriminates between subjective and objective familiarity and novelty.

    PubMed

    Kafkas, Alexandros; Montaldi, Daniela

    2015-10-01

    The pupil response discriminates between old and new stimuli, with old stimuli characterized by larger pupil dilation patterns than new stimuli. We sought to explore the cause of the pupil old/new effect and discount the effect of targetness, effort, recollection retrieval, and complexity of the recognition decision. Two experiments are reported in which the pupil response and the eye fixation patterns were measured, while participants identified novel and familiar object stimuli, in two separate tasks, emphasizing either novelty or familiarity detection. In Experiment 1, familiarity and novelty decisions were taken using a rating scale, while in Experiment 2 a simpler yes/no decision was used. In both experiments, we found that detection of target familiar stimuli resulted in greater pupil dilation than the detection of target novel stimuli, while the duration of the first fixation discriminated between familiar and novel stimuli as early as within 320 ms after stimulus onset. Importantly, the pupil response distinguished between the objective (during an earlier temporal component) and the subjective (during a later temporal component) status of the stimulus for misses and false alarms. In the light of previous findings, we suggest that the pupil and fixation old/new effects reflect the distinct neural and cognitive mechanisms involved in the familiarity and novelty decisions. The findings also have important implications for the use of pupil dilation and eye movement patterns to explore explicit and implicit memory processes.

  11. Effects of methylphenidate on responses to novelty in a teleost fish (Poecilia reticulata).

    PubMed

    De Serrano, Alex R; Fong, Charmaine; Rodd, F Helen

    2016-04-01

    Novelty seeking, the willingness to explore novel stimuli, can have important fitness consequences. The neurotransmitter dopamine has been linked to this behavior in studies on lab animals including rodents and fish; however, few studies have investigated this association in individuals from natural populations. Trinidadian guppies (Poecilia reticulata) show variation in willingness to explore novel objects and environments, and females tend to show a preference for novel males. In this study, we asked whether we could enhance interest in several types of novel stimuli in lab-reared, female Trinidadian guppies by administering methylphenidate hydrochloride, a stimulant known to increase dopamine levels. We scored their responses to three different types of novelty: novel environments, objects, and males. Treated females showed enhanced exploratory behavior: they traversed relatively more inner squares of the novel environment (open-field test); they spent more time inspecting a novel object; and they showed greater interest in the second male guppy to which they were exposed than control fish. We also found a positive association between our metrics of exploration in the open field and novel object tests. Our other assays suggest that these differences were not the result of increased activity or reduced levels of stress. Therefore, our results suggest that dopamine plays a role in the responsiveness of guppies to novelty; this opens the door to studies of behavioral mechanisms in natural populations. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Altered locomotor and stereotyped responses to acute methamphetamine in adolescent, maternally separated rats.

    PubMed

    Pritchard, Laurel M; Hensleigh, Emily; Lynch, Sarah

    2012-09-01

    Neonatal maternal separation (MS) has been used to model the effects of early life stress in rodents. MS alters behavioral responses to a variety of abused drugs, but few studies have examined its effects on methamphetamine sensitivity. We sought to determine the effects of MS on locomotor and stereotyped responses to low-to-moderate doses of methamphetamine in male and female adolescent rats. Male and female rat pups were subjected to 3 h per day of MS on postnatal days (PN) 2-14 or a brief handling control procedure during the same period. During adolescence (approximately PN 40), all rats were tested for locomotor activity and stereotyped behavior in response to acute methamphetamine administration (0, 1.0, or 3.0 mg/kg, s.c.). MS rats of both sexes exhibited increased locomotor activity in a novel environment, relative to handled controls. MS increased the locomotor response to methamphetamine (METH), and this effect occurred at different doses for male (3.0 mg/kg) and female (1.0 mg/kg) rats. MS also increased stereotyped behavior in response to METH (1.0 mg/kg) in both sexes. MS enhances the locomotor response to METH in a dose- and sex-dependent manner. These results suggest that individuals with a history of early life stress may be particularly vulnerable to the psychostimulant effects of METH, even at relatively low doses.

  13. Evolutionary novelties.

    PubMed

    Wagner, Günter P; Lynch, Vincent J

    2010-01-26

    How novel traits arise in organisms has long been a major problem in biology. Indeed, the sharpest critiques of Darwin's theory of evolution by natural selection often centered on explaining how novel body parts arose. In his response to The Origin of Species, St. George J. Mivart challenged Darwin to explain the origin of evolutionary novelties such as the mammary gland, asking if it was "conceivable that the young of any animal was ever saved from destruction by accidentally sucking a drop of scarcely nutritious fluid from an accidentally hypertrophied cutaneous gland of its mother?" It is only now that modern molecular and genomic tools are being brought to bear on this question that we are finally in a position to answer Mivart's challenge and explain one of the most fundamental questions of biology: how does novelty arise in evolution?

  14. A Role for Casein Kinase 1 Epsilon in the Locomotor Stimulant Response to Methamphetamine

    PubMed Central

    Bryant, Camron D.; Graham, Melissa E.; Distler, Margaret G.; Munoz, Michaelanne B.; Li, Dongdong; Vezina, Paul; Sokoloff, Greta; Palmer, Abraham A.

    2009-01-01

    Rationale We previously co-localized a quantitative trait locus (QTL) for sensitivity to the locomotor stimulant effect of methamphetamine (MA) with a QTL for expression of casein kinase 1 epsilon (Csnk1-ε) in the nucleus accumbens (NAc). Subsequently, we identified a single nucleotide polymorphism in CSNK1E (rs135745) that was associated with increased sensitivity to the subjective effects of d-amphetamine in healthy human subjects. Based on these results, we hypothesized that differential expression of Csnk1-ε causes differential sensitivity to MA-induced locomotor activity in mice. Objective In the present study, we used PF-670462 (PF), which is a selective inhibitor of Csnk1-ε, to directly evaluate the role of Csnk1-ε in the locomotor response to MA in male C57BL/6J mice. Methods We administered vehicle, PF, MA or MA+PF, either via intraperitoneal injections or bilateral intra-NAc microinjections. We also examined Darpp-32 phosphorylation in mice receiving intraperitoneal injections. Results Intraperitoneal PF (20-40 mg/kg) attenuated the locomotor response to MA (2 mg/kg) without affecting baseline activity. The high dose of PF also significantly inhibited MA-induced phosphorylation of Darpp-32, providing a potential mechanism by which Csnk1-ε contributes to MA-induced locomotor activity. Furthermore, microinjection of PF (5 μg/side) into the NAc completely blocked the locomotor response to MA (2.5 μg/side) without affecting baseline activity. Conclusions These results provide direct evidence that Csnk1-ε is crucial for the locomotor stimulant response to a moderate dose of MA and are consistent with the hypothesis that genetic polymorphisms in Csnk1-ε influence sensitivity to amphetamines in both mice and humans. PMID:19050854

  15. Novelty and emotion: Pupillary and cortical responses during viewing of natural scenes.

    PubMed

    Ferrari, Vera; De Cesarei, Andrea; Mastria, Serena; Lugli, Luisa; Baroni, Giulia; Nicoletti, Roberto; Codispoti, Maurizio

    2016-01-01

    Given the remarkable similarities in the antecedent conditions-stimulus motivational relevance and novelty (i.e., probability of occurrence)-that elicit amplitude modulation of the late positive potential (LPP) and the pupillary dilation response, the present study examines whether these two indexes of orienting response reflect common processes that are responsible for modulatory patterns in motivationally relevant contexts. In the present study, the LPP and the pupillary dilation response were co-registered in a free-picture viewing context in which stimulus novelty was manipulated through repeated presentation of the same picture exemplar. More specifically, pictures depicting both emotional and neutral contents could be novel, that is never seen before in the course of the study, or repeated 4-8 times in a row (i.e., massed repetition). Results showed that, despite massed repetitions, the late positive potential amplitude continued to be highly modulated by picture content, whereas affective modulation of pupil dilation decreased with picture repetition. These findings indicate that, although the LPP and pupil dilation are similarly affected by motivational relevance during the viewing of novel pictures, they differ when pictures are highly familiar, possibly reflecting different functional meanings in the context of the orienting response. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Effects of voluntary wheel running on heart rate, body temperature, and locomotor activity in response to acute and repeated stressor exposures in rats

    PubMed Central

    MASINI, CHER V.; NYHUIS, TARA J.; SASSE, SARAH K.; DAY, HEIDI E. W.; CAMPEAU, SERGE

    2015-01-01

    Stress often negatively impacts physical and mental health but it has been suggested that voluntary physical activity may benefit health by reducing some of the effects of stress. The present experiments tested whether voluntary exercise can reduce heart rate, core body temperature and locomotor activity responses to acute (novelty or loud noise) or repeated stress (loud noise). After 6 weeks of running-wheel access, rats exposed to a novel environment had reduced heart rate, core body temperature, and locomotor activity responses compared to rats housed under sedentary conditions. In contrast, none of these measures were different between exercised and sedentary rats following acute 30-min noise exposures, at either 85 or 98 dB. Following 10 weeks of running-wheel access, both groups displayed significant habituation of all these responses to 10 consecutive daily 30-min presentations of 98 dB noise stress. However, the extent of habituation of all three responses was significantly enhanced in exercised compared to sedentary animals on the last exposure to noise. These results suggest that in physically active animals, under some conditions, acute responses to stress exposure may be reduced, and response habituation to repeated stress may be enhanced, which ultimately may reduce the negative and cumulative impact of stress. PMID:21438772

  17. Effects of voluntary wheel running on heart rate, body temperature, and locomotor activity in response to acute and repeated stressor exposures in rats.

    PubMed

    Masini, Cher V; Nyhuis, Tara J; Sasse, Sarah K; Day, Heidi E W; Campeau, Serge

    2011-05-01

    Stress often negatively impacts physical and mental health but it has been suggested that voluntary physical activity may benefit health by reducing some of the effects of stress. The present experiments tested whether voluntary exercise can reduce heart rate, core body temperature and locomotor activity responses to acute (novelty or loud noise) or repeated stress (loud noise). After 6 weeks of running-wheel access, rats exposed to a novel environment had reduced heart rate, core body temperature, and locomotor activity responses compared to rats housed under sedentary conditions. In contrast, none of these measures were different between exercised and sedentary rats following acute 30-min noise exposures, at either 85 or 98 dB. Following 10 weeks of running-wheel access, both groups displayed significant habituation of all these responses to 10 consecutive daily 30-min presentations of 98 dB noise stress. However, the extent of habituation of all three responses was significantly enhanced in exercised compared to sedentary animals on the last exposure to noise. These results suggest that in physically active animals, under some conditions, acute responses to stress exposure may be reduced, and response habituation to repeated stress may be enhanced, which ultimately may reduce the negative and cumulative impact of stress.

  18. Models of anxiety: responses of rats to novelty in an open space and an enclosed space.

    PubMed

    Ennaceur, A; Michalikova, S; Chazot, P L

    2006-07-15

    Exposure to novelty has been shown to induce anxiety responses in a variety of behavioural paradigms. The purpose of the present study was to investigate whether exposition of naïve rats to novelty would result in a comparable or a different pattern of responses in an open space versus enclosed space with or without the presence of an object in the centre of the field. Lewis and Wistar rats of both genders were used to illustrate and discuss the value and validity of these anxiety paradigms. We examined a wide range of measures, which cover several aspects of animals' responses. The results of this study revealed significant differences between the behaviour of animals in an open space and in the enclosed space. It also revealed significant differences in animal's responses to the presence and absence of an object in the open space and in the enclosed space. In the enclosed space, rats spent most of their time in the outer area with lower number of exits and avoided the object area except when there was an object, while in the open space rats displayed frequent short duration re-entries in the outer area and spent longer time in the object area in presence of an object. The time spent in the inner area (away from the outer area and the object area) was significantly longer and the number of faecal boli was significantly higher in the open space than in the enclosed space. In the present report, we will discuss the fundamental differences between enclosed space and open space models, and we will examine some methodological issues related to the current animal models of human behaviour in anxiety. In the enclosed space, animals can avoid the potential threat associated with the centre area of a box and chose the safety of walls and corners, whereas, in the open space animals have to avoid every parts of the field from which there was no safe escape. The response of animals to novelty in an open space model appears more relevant to anxiety than in an enclosed space

  19. Dissociating anxiolytic and sedative effects of GABAAergic drugs using temperature and locomotor responses to acute stress

    PubMed Central

    Klanker, Marianne; Groenink, Lucianne; Korte, S. Mechiel; Cook, James M.; Van Linn, Michael L.; Hopkins, Seth C.; Olivier, Berend

    2009-01-01

    Rationale The stress-induced hyperthermia (SIH) model is an anxiety model that uses the transient rise in body temperature in response to acute stress. Benzodiazepines produce anxiolytic as well as sedative side effects through nonselective binding to GABAA receptor subunits. The GABAA receptor α1 subunit is associated with sedation, whereas the GABAA receptor α2 and α3 subunits are involved in anxiolytic effects. Objectives We therefore examined the effects of (non) subunit-selective GABAA receptor agonists on temperature and locomotor responses to novel cage stress. Results Using telemetric monitoring of temperature and locomotor activity, we found that nonsubunit-selective GABAA receptor agonist diazepam as well as the α3 subunit-selective receptor agonist TP003 dose-dependently attenuated SIH and locomotor responses. Administration of GABAA receptor α1-selective agonist zolpidem resulted in profound hypothermia and locomotor sedation. The GABAA receptor α1-selective antagonist βCCt antagonized the hypothermia, but did not reverse the SIH response attenuation caused by diazepam and zolpidem. These results suggest an important regulating role for the α1 subunit in thermoregulation and sedation. Ligands of extrasynaptic GABAA receptors such as alcohol and nonbenzodiazepine THIP attenuated the SIH response only at high doses. Conclusions The present study confirms a putative role for the GABAA receptor α1 subunit in hypothermia and sedation and supports a role for α2/3 subunit GABAA receptor agonists in anxiety processes. In conclusion, we show that home cage temperature and locomotor responses to novel home cage stress provide an excellent tool to assess both anxiolytic and sedative effects of various (subunit-selective) GABAAergic compounds. PMID:19169673

  20. Food deprivation increases the low-dose locomotor stimulant response to ethanol in Drosophila melanogaster.

    PubMed

    Kliethermes, Christopher L

    2013-10-01

    Acute and chronic states of food deprivation result in increased sensitivity to a variety of natural reinforcers as well as to drugs of abuse. Food deprived animals show increased locomotor activity during periods of food deprivation, as well as increased locomotor stimulant responses to drugs of abuse, including cocaine, amphetamine, morphine, and ethanol, implying that drugs of abuse act in part on neural systems that underlie responses towards food. To determine whether this effect extends to an invertebrate, highly genetically tractable animal, the locomotor stimulant effects of low dose ethanol were assessed under a variety of feeding conditions in the fruit fly, Drosophila melanogaster. Food deprivation resulted in strain specific increases in ethanol-stimulated locomotor activity in most strains tested, although elevated baseline activity confounded interpretation in some strains. Experiments conducted with Canton S flies found that the effects of food deprivation on the locomotor stimulant response to ethanol increased with the duration of deprivation, and could be blocked by refeeding the flies with standard food or sucrose, but not yeast, immediately prior to the ethanol exposure. Life-span extending dietary depletion procedures or previous periods of food deprivation did not affect the response to ethanol, indicating that only animals in an acutely food deprived state are more sensitive to the stimulant effects of ethanol. These results suggest that increased sensitivity to the stimulant effects of some drugs of abuse might reflect an evolutionarily conserved neural mechanism that underlies behavioral responses to natural reinforcers and drugs of abuse. The identification of this mechanism, and the genes that underlie its development and function, will constitute a novel approach towards the study of alcohol abuse and dependence.

  1. Brain transcription factor gene expression, neurotransmitter levels, and novelty response behaviors: alterations during rat amphetamine withdrawal and following chronic injection stress.

    PubMed

    Persico, A M; Schindler, C W; Zaczek, R; Brannock, M T; Uhl, G R

    1995-03-01

    Transcription factors are known to act as gene expression regulators, possibly linking extracellular stimuli to long-term modifications at the neuronal level. Such modifications may potentially underlie chronic psychostimulant- and stress-induced behavioral alterations. This study illustrates how a 2 week, twice daily 7.5 mg/kg d-amphetamine or saline regimen alters rat brain regional expression of transcription factor genes, including c-fos, fos-B, jun-B, c-jun, and zif 268, and seeks potential correlations between those changes and alterations in neurotransmitter levels and behavioral novelty responses. Amphetamine withdrawal-induced decreases in transcription factor mRNA levels, assessed using Northern blot analysis, appear most prominent in prefrontal cortex, begin approximately 12 h after the last injection, and largely recover to control levels by 54 h. Prefrontal cortical and striatal dopamine content, assessed using HPLC, decrease and recover over a similar time course. Behavioral "stereotypy time" manifest by animals exposed to a novel environment, a measure sensitive to psychostimulant withdrawal, also decreases beginning 12 h after the last injection, is still significantly reduced at 54 h, and recovers at 72 h. Chronic saline injections are followed by a consistent decrease in transcription factor gene expression, observed 6 h after the last injection, followed by a "rebound" increase at 12 h. These changes are accompanied by dramatic, mostly biphasic alterations in prefrontal cortical biogenic amines and by a short-lived increase in striatal dopamine turnover. At the same time, rats display much longer-lasting decreases in locomotor responses when exposed to a novel environment, with recovery occurring only 54 h after the last injection. The delayed recovery of behavioral responses to novelty is consistent with potential involvement of changes in transcription factor-mediated gene expression in neurochemical mechanisms underlying psychostimulant

  2. Locomotor training modifies soleus monosynaptic motoneuron responses in human spinal cord injury.

    PubMed

    Smith, Andrew C; Rymer, William Zev; Knikou, Maria

    2015-01-01

    The objective of this study was to assess changes in monosynaptic motoneuron responses to stimulation of Ia afferents after locomotor training in individuals with chronic spinal cord injury (SCI). We hypothesized that locomotor training modifies the amplitude of the soleus monosynaptic motoneuron responses in a body position-dependent manner. Fifteen individuals with chronic clinical motor complete or incomplete SCI received an average of 45 locomotor training sessions. The soleus H-reflex and M-wave recruitment curves were assembled using data collected in both the right and left legs, with subjects seated and standing, before and after training. The soleus H-reflexes and M-waves, measured as peak-to-peak amplitudes, were normalized to the maximal M-wave (M(max)). Stimulation intensities were normalized to 50% M(max) stimulus intensity. A sigmoid function was also fitted to the normalized soleus H-reflexes on the ascending limb of the recruitment curve. After training, soleus H-reflex excitability was increased in both legs in AIS C subjects, and remained unchanged in AIS A-B and AIS D subjects during standing. When subjects were seated, soleus H-reflex excitability was decreased after training in many AIS C and D subjects. Changes in reflex excitability coincided with changes in stimulation intensities at H-threshold, 50% maximal H-reflex, and at maximal H-reflex, while an interaction between leg side and AIS scale for the H-reflex slope was also found. Adaptations of the intrinsic properties of soleus motoneurons and Ia afferents, the excitability profile of the soleus motoneuron pool, oligosynaptic inputs, and corticospinal inputs may all contribute to these changes. The findings of this study demonstrate that locomotor training impacts the amplitude of the monosynaptic motoneuron responses based on the demands of the motor task in people with chronic SCI.

  3. Locomotor training modifies soleus monosynaptic motoneuron responses in human spinal cord injury

    PubMed Central

    Smith, Andrew C.; Rymer, William Zev

    2015-01-01

    The objective of this study was to assess changes in monosynaptic motoneuron responses to stimulation of Ia afferents after locomotor training in individuals with chronic spinal cord injury (SCI). We hypothesized that locomotor training modifies the amplitude of the soleus monosynaptic motoneuron responses in a body position-dependent manner. Fifteen individuals with chronic clinical motor complete or incomplete SCI received an average of 45 locomotor training sessions. The soleus H-reflex and M-wave recruitment curves were assembled using data collected in both the right and left legs, with subjects seated and standing, before and after training. The soleus H-reflexes and M-waves, measured as peak-to-peak amplitudes, were normalized to the maximal M-wave (Mmax). Stimulation intensities were normalized to 50 % Mmax stimulus intensity. A sigmoid function was also fitted to the normalized soleus H-reflexes on the ascending limb of the recruitment curve. After training, soleus H-reflex excitability was increased in both legs in AIS C subjects, and remained unchanged in AIS A-B and AIS D subjects during standing. When subjects were seated, soleus H-reflex excitability was decreased after training in many AIS C and D subjects. Changes in reflex excitability coincided with changes in stimulation intensities at H-threshold, 50 % maximal H-reflex, and at maximal H-reflex, while an interaction between leg side and AIS scale for the H-reflex slope was also found. Adaptations of the intrinsic properties of soleus motoneurons and Ia afferents, the excitability profile of the soleus motoneuron pool, oligosynaptic inputs, and corticospinal inputs may all contribute to these changes. The findings of this study demonstrate that locomotor training impacts the amplitude of the monosynaptic motoneuron responses based on the demands of the motor task in people with chronic SCI. PMID:25205562

  4. Differential roles of GABAB1 subunit isoforms on locomotor responses to acute and repeated administration of cocaine.

    PubMed

    Jacobson, Laura H; Sweeney, Fabian F; Kaupmann, Klemens; O'Leary, Olivia F; Gassmann, Martin; Bettler, Bernhard; Cryan, John F

    2016-02-01

    GABAB receptors are crucial modulators of the behavioural effects of drug abuse, and agonists and positive allosteric modulators show promise as pharmacological strategies for anti-addiction therapeutics. GABAB receptors are functional heterodimers of GABAB1 and GABAB2 subunits. The predominant neuronal GABAB1 subunit isoforms are GABAB1a and GABAB1b. Selective ablation of these isoforms in mice revealed differential behavioural responses in fear, cognition and stress sensitivity. However, the influence of the two GABAB1 isoforms on responses to drugs of abuse is unclear. Therefore we examined the responses of GABAB1 subunit isoform null mice to cocaine in acute locomotor activity and conditioned place preference (CPP) paradigms. During habituation for the acute locomotor activity assay, GABAB1b(-/-) mice showed higher levels of locomotor activity relative to wild-type (WT) and GABAB1a(-/-) mice, in accordance with previous studies. Acute cocaine (10 mg/kg) increased locomotor activity in habituated mice of all three genotypes, with GABAB1a(-/-) mice showing sustained hyperlocomotor responses 30 min after cocaine relative to WT and GABAB1b(-/-) mice. No genotypes demonstrated a cocaine-induced place preference, however, GABAB1a(-/-) mice demonstrated enhanced locomotor sensitisation to chronic cocaine in the CPP paradigm in comparison to WT mice, whereas GABAB1b(-/-) mice failed to develop locomotor sensitisation, despite higher levels of basal locomotor activity. These findings indicate that GABAB1a and GABAB1b isoforms differentially regulate behavioural responses to cocaine, with deletion of GABAB1a enhancing cocaine-induced locomotor activity and deletion of GABAB1b protecting from cocaine-induced sensitisation.

  5. 5-HT1A Agonist Properties Contribute to a Robust Response to Vilazodone in the Novelty Suppressed Feeding Paradigm

    PubMed Central

    Garcia-Garcia, Alvaro L.; Navarro-Sobrino, Míriam; Pilosof, Gila; Banerjee, Pradeep; Dranovsky, Alex

    2016-01-01

    Background: Differences in 5-HT1A receptor function have been implicated in vulnerability to depression and in response to treatment. Adding 5-HT1A partial agonists to selective serotonin reuptake inhibitors has been touted as a strategy to increase their efficacy. Here we use the novelty suppressed feeding paradigm to compare the effects of vilazodone, a high-potency selective serotonin reuptake inhibitor, with high affinity for 5-HT1A receptors to the reference selective serotonin reuptake inhibitor fluoxetine across several mouse strains that differ in their response to selective serotonin reuptake inhibitors. Methods: To confirm 5-HT1A agonist activity, body temperature was measured after acute administration of vilazodone or fluoxetine, as administration of 5-HT1A agonists induces hypothermia. We next used 3 strains of mice to examine the effects of the drugs on latency in the novelty suppressed feeding, a paradigm generally sensitive to chronic but not acute effects of antidepressants. Results: Vilazodone induces robust hypothermia and blocks stress-induced hyperthermia in a 5-HT1A-dependent manner, consistent with agonist effects at 5-HT1A autoreceptors. In 129SvEv mice, vilazodone (10mg/kg/d) reduces the latency to eat in the novelty suppressed feeding test within 8 days, while no effect of fluoxetine (20mg/kg/d) was detected at that time. In contrast, both vilazodone and fluoxetine are effective at decreasing latency to eat in the novelty suppressed feeding paradigm in a strain with low autoreceptor levels. In mice with higher autoreceptor levels, no significant difference was detected between fluoxetine and vehicle (P=.8) or vilazodone and vehicle (P=.06). Conclusion: In mice, vilazodone may offer advantages in time of onset and efficacy over a reference selective serotonin reuptake inhibitor in the novelty suppressed feeding test. PMID:27352617

  6. Influence of locomotor muscle afferent inhibition on the ventilatory response to exercise in heart failure.

    PubMed

    Olson, Thomas P; Joyner, Michael J; Eisenach, John H; Curry, Timothy B; Johnson, Bruce D

    2014-02-01

    What is the central question of this study? Patients with heart failure often develop ventilatory abnormalities at rest and during exercise, but the mechanisms underlying these abnormalities remain unclear. This study investigated the influence of inhibiting afferent neural feedback from locomotor muscles on the ventilatory response during exercise in heart failure patients. What is the main finding and its importance? Our results suggest that inhibiting afferent feedback from locomotor muscle via intrathecal opioid administration significantly reduces the ventilatory response to exercise in heart failure patients. Patients with heart failure (HF) develop ventilatory abnormalities at rest and during exercise, but the mechanism(s) underlying these abnormalities remain unclear. We examined whether the inhibition of afferent neural feedback from locomotor muscles during exercise reduces exercise ventilation in HF patients. In a randomized, placebo-controlled design, nine HF patients (age, 60 ± 2 years; ejection fraction, 27 ± 2%; New York Heart Association class 2 ± 1) and nine control subjects (age, 63 ± 2 years) underwent constant-work submaximal cycling (65% peak power) with intrathecal fentanyl (impairing the cephalad projection of opioid receptor-sensitive afferents) or sham injection. The hypercapnic ventilatory response was measured to determine whether cephalad migration of fentanyl occurred. There were no differences in hypercapnic ventilatory response within or between groups in either condition. Despite a lack of change in ventilation, tidal volume or respiratory rate, HF patients had a mild increase in arterial carbon dioxide (P(aCO(2)) and a decrease in oxygen (P(aO(2)); P < 0.05 for both) at rest. The control subjects demonstrated no change in P(aCO(2)), P(aO(2)), ventilation, tidal volume or respiratory rate at rest. In response to fentanyl during exercise, HF patients had a reduction in ventilation (63 ± 6 versus 44 ± 3 l min(-1), P < 0.05) due

  7. Novelty Seeking, Harm Avoidance, and Cerebral Responses to Conflict Anticipation: An Exploratory Study

    PubMed Central

    Hu, Jianping; Hu, Sien; Maisano, Julianna R.; Chao, Herta H.; Zhang, Sheng; Li, Chiang-Shan R.

    2016-01-01

    Proactive control allows us to maneuver a changing environment and individuals are distinct in how they anticipate and approach such changes. Here, we examined how individual differences in personality traits influence cerebral responses to conflict anticipation, a critical process of proactive control. We explored this issue in an fMRI study of the stop signal task, in which the probability of stop signal – p(Stop) – was computed trial by trial with a Bayesian model. Higher p(Stop) is associated with prolonged go trial reaction time, indicating conflict anticipation and proactive control of motor response. Regional brain activations to conflict anticipation were correlated to novelty seeking (NS), harm avoidance (HA), reward dependence, as assessed by the Tridimensional Personality Questionnaire, with age and gender as covariates, in a whole-brain linear regression. Results showed that increased anticipation of the stop signal is associated with activations in the bilateral inferior parietal lobules (IPL), right lateral orbitofrontal cortex (lOFC), middle frontal gyrus (MFG), anterior pre-supplementary motor area (pre-SMA), and bilateral thalamus, with men showing greater activation in the IPL than women. NS correlated negatively to activity in the anterior pre-SMA, right IPL, and MFG/lOFC, and HA correlated negatively to activity in the thalamus during conflict anticipation. In addition, the negative association between NS and MFG/lOFC activity was significant in men but not in women. Thus, NS and HA traits are associated with reduced mobilization of cognitive control circuits when enhanced behavioral control is necessary. The findings from this exploratory study characterize the influence of NS and HA on proactive control and provide preliminary evidence for gender differences in these associations. PMID:27857686

  8. Localization of the event-related potential novelty response as defined by principal components analysis.

    PubMed

    Dien, Joseph; Spencer, Kevin M; Donchin, Emanuel

    2003-10-01

    Recent research indicates that novel stimuli elicit at least two distinct components, the Novelty P3 and the P300. The P300 is thought to be elicited when a context updating mechanism is activated by a wide class of deviant events. The functional significance of the Novelty P3 is uncertain. Identification of the generator sources of the two components could provide additional information about their functional significance. Previous localization efforts have yielded conflicting results. The present report demonstrates that the use of principal components analysis (PCA) results in better convergence with knowledge about functional neuroanatomy than did previous localization efforts. The results are also more convincing than that obtained by two alternative methods, MUSIC-RAP and the Minimum Norm. Source modeling on 129-channel data with BESA and BrainVoyager suggests the P300 has sources in the temporal-parietal junction whereas the Novelty P3 has sources in the anterior cingulate.

  9. Models of anxiety: responses of mice to novelty and open spaces in a 3D maze.

    PubMed

    Ennaceur, A; Michalikova, S; van Rensburg, R; Chazot, P L

    2006-11-01

    The present report describes the emotional responses of different strains of mice to exposure to a novel open space model of anxiety using a 3D spatial navigation task. The 3D maze is modification of the radial maze with flexible arms that can be raised above or lowered below the horizontal level of a central platform. To access the arms animals need to cross a bridge linking the arms to the central platform. In this model, mice are exposed to novelty in an unfamiliar open space setting with no safe alternative. Fear from novelty is compounded with the need to explore. The drive to escape and the drive to approach are intermingled making this open space model radically different from the current models of anxiety which provide animals with the choice between safe and anxiogenic spaces. In a series of experiments, we examined the behaviour of different groups of mice from C57, C3H, CD1 and Balb/c strains. In the first experiment, different groups of C57 mice were tested in one of the three arms configurations. In the second experiment, C57 mice were compared to C3H mice. In the third experiment, C57 mice were compared to CD1 and Balb/c mice in the raised arm configuration over three successive sessions. In the fourth experiment, we examined the behaviour of C57 mice in the lowered arm configuration with an open and an enclosed central. In the final experiment, we examined the difference between C57 and C3H mice of both genders. Using several spatio-temporal parameters of the transition responses between central platform, bridges and arms, we have been able to show consistent results demonstrating significant differences between C57 and C3H mice, and between Balb/c and both C57 and CD1 mice. C3H appear more anxious than C57 mice, and Balb/c mice seem more anxious than C57 and CD1 mice. We also observed significant differences between sexes in C3H mice but not in C57 mice. C3H male mice appear more anxious than C3H female mice and than both C57 male and female mice

  10. Exploration of a novel object in late adolescence predicts novelty-seeking behavior in adulthood: Associations among behavioral responses in four novelty-seeking tests.

    PubMed

    Cuenya, Lucas; Sabariego, Marta; Donaire, Rocío; Callejas-Aguilera, José Enrique; Torres, Carmen; Fernández-Teruel, Alberto

    2016-04-01

    The sensation/novelty seeking behavioral trait refers to the exploration/preference for a novel environment. Novelty seeking increases during late adolescence and it has been associated with several neurobehavioral disorders. In this experiment, we asked whether inbred Roman high- and low-avoidance (RHA-I, RLA-I) rats (1) differ in novelty seeking in late adolescence and (2) whether late adolescent novelty seeking predicts this trait in adulthood. Thirty six male RHA-I and 36 RLA-I rats were exposed to a novel object exploration (NOE) test during late adolescence (pnd: 52-59; contact latency, contact time, contact frequency). Head-dipping (hole-board, HB), time and visits to a novel-arm (Y-maze), and latency-in and emergence latency (emergence test) were registered in adulthood (pnd: 83-105). The results showed strain differences in all these tests (RHA-I>RLA-I). Factor analysis (RHA-I+RLA-I) revealed two clusters. The first one grouped HB and emergence test measures. The second one grouped NOE and Y-maze variables. Time exploring a novel object (NOE) was a significant predictor of novel arm time (RHA-I+RLA, RHA-I); contact latency was a significant predictor of novel arm frequency (RLA-I). Present results show consistent behavioral associations across four novelty-seeking tests and suggest that late adolescent novelty seeking predicts this genetically-influenced temperamental trait in adult Roman rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Adaptability: How Students' Responses to Uncertainty and Novelty Predict Their Academic and Non-Academic Outcomes

    ERIC Educational Resources Information Center

    Martin, Andrew J.; Nejad, Harry G.; Colmar, Susan; Liem, Gregory Arief D.

    2013-01-01

    Adaptability is defined as appropriate cognitive, behavioral, and/or affective adjustment in the face of uncertainty and novelty. Building on prior measurement work demonstrating the psychometric properties of an adaptability construct, the present study investigates dispositional predictors (personality, implicit theories) of adaptability, and…

  12. Adaptability: How Students' Responses to Uncertainty and Novelty Predict Their Academic and Non-Academic Outcomes

    ERIC Educational Resources Information Center

    Martin, Andrew J.; Nejad, Harry G.; Colmar, Susan; Liem, Gregory Arief D.

    2013-01-01

    Adaptability is defined as appropriate cognitive, behavioral, and/or affective adjustment in the face of uncertainty and novelty. Building on prior measurement work demonstrating the psychometric properties of an adaptability construct, the present study investigates dispositional predictors (personality, implicit theories) of adaptability, and…

  13. Electrophysiological Responses to Auditory Novelty in Temperamentally Different 9-Month-Old Infants

    ERIC Educational Resources Information Center

    Marshall, Peter J.; Reeb, Bethany C.; Fox, Nathan A.

    2009-01-01

    Behavioral reactivity to novel stimuli in the first half-year of life has been identified as a key aspect of early temperament and a significant precursor of approach and withdrawal tendencies to novelty in later infancy and early childhood. The current study examines the neural signatures of reactivity to novel auditory stimuli in 9-month-old…

  14. Machine learning methods predict locomotor response to MK-801 in mouse models of down syndrome.

    PubMed

    Nguyen, Cao D; Costa, Alberto C S; Cios, Krzysztof J; Gardiner, Katheleen J

    2011-03-01

    Down syndrome (DS), caused by trisomy of human chromosome 21 (HSA21), is a common genetic cause of cognitive impairment. This disorder results from the overexpression of HSA21 genes and the resulting perturbations in many molecular pathways and cellular processes. Knowledge-based identification of targets for pharmacotherapies will require defining the most critical protein abnormalities among these many perturbations. Here the authors show that using the Ts65Dn and Ts1Cje mouse models of DS, which are trisomic for 88 and 69 reference protein coding genes, respectively, a simple linear Naïve Bayes classifier successfully predicts behavioral outcome (level of locomotor activity) in response to treatment with the N-methyl-d-aspartate (NMDA) receptor antagonist MK-801. Input to the Naïve Bayes method were simple protein profiles generated from cortex and output was locomotor activity binned into three levels: low, medium, and high. When Feature Selection was used with the Naïve Bayes method, levels of three HSA21 and two non-HSA21 protein features were identified as making the most significant contributions to activity level. Using these five features, accuracies of up to 88% in prediction of locomotor activity were achieved. These predictions depend not only on genotype-specific differences but also on within-genotype individual variation in levels of molecular and behavioral parameters. With judicious choice of pathways and components, a similar approach may be useful in analysis of more complex behaviors, including those associated with learning and memory, and may facilitate identification of novel targets for pharmacotherapeutics.

  15. Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine.

    PubMed

    Duclot, Florian; Perez-Taboada, Iara; Wright, Katherine N; Kabbaj, Mohamed

    2016-10-01

    Only a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear responses of rats selected for their high (high responders, HR) or low (low responders, LR) exploration of a novel environment, indicator of novelty seeking. While HR and LR rats exhibited similar sensitivity to the shock and cued fear memory retention, fewer extinction sessions were required in HR than LR animals to reach extinction, indicating faster contextual and cued memory extinction. In a second part, we found an effective disruption of contextual fear reconsolidation by the N-methyl-d-aspartate receptor antagonist ketamine, associated with a down-regulation of early growth response 1 (Egr1) in the hippocampal CA1 area, and up-regulation of brain-derived neurotrophic factor (Bdnf) mRNA levels in the prelimbic and infralimbic cortices. Altogether, these data demonstrate a link between novelty seeking and conditioned fear extinction, and highlight a promising novel role of ketamine in affecting established fear memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Effect of drugs that alter alertness and emotionality on the novelty response of a weak electric fish, Gymnotus carapo.

    PubMed

    Aparecida, S; Corrêa, L; Hoffmann, A

    Weak field electric fish respond to alerting stimuli with a transient increase in the frequency of electric organ discharge (novelty response). In an attempt to demonstrate the influence of different degrees of alertness and of emotionality on the novelty response of Gymnotus carapo, we studied the variations in the magnitude of this response induced by the application of an electric stimulus to the water of the experimental box using a pair of electrodes, before and after intramuscular injections of d-amphetamine (1-2 and 4 mg/kg), sodium pentobarbital (10-20 and 30 mg/kg), diazepam (1-2 and 4 mg/kg), beta-carboline (2 mg/kg), and saline. After d-amphetamine injection the animal presented increased somatic motility but no changes in electric organ baseline firing rate or in response to the alerting electric stimulus. Sodium pentobarbital induced a partial loss of posture and a reduction of fin and operculum movements, as well as a reduction of baseline firing rate and of the response to the alerting electric stimulus, with frequent interruptions in electric organ firing. Beta-carboline caused increased motility, but no changes in basal firing rate or in response to the alerting stimulus. Diazepan-injected fishes remained still throughout the experiment, and some of those threated with the higher dose (4 mg/kg) presented interruptions on electric organ discharges in response to stimulation but no change on baseline firing rate. The data suggest that a reduction of the degree of alertness by the barbiturate and a decrease in emotionality and/or stress by the benzodiazepine interfere with the novelty response. The possible site of action of the drugs is discussed.

  17. Exaggerated sympathetic and cardiovascular responses to stimulation of the mesencephalic locomotor region in spontaneously hypertensive rats.

    PubMed

    Liang, Nan; Mitchell, Jere H; Smith, Scott A; Mizuno, Masaki

    2016-01-01

    The sympathetic and pressor responses to exercise are exaggerated in hypertension. However, the underlying mechanisms causing this abnormality remain to be fully elucidated. Central command, a neural drive originating in higher brain centers, is known to activate cardiovascular and locomotor control circuits concomitantly. As such, it is a viable candidate for the generation of the augmented vascular response to exercise in this disease. We hypothesized that augmentations in central command function contribute to the heightened cardiovascular response to exercise in hypertension. To test this hypothesis, changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to electrical stimulation of mesencephalic locomotor region (MLR; 20-50 μA in 10-μA steps evoking fictive locomotion), a putative component of the central command pathway, were examined in decerebrate, paralyzed normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tibial nerve discharge during MLR stimulation significantly increased in an intensity-dependent manner in both WKY and SHR but was not different between groups. Stimulation of the MLR evoked significantly larger increases in RSNA and MAP with increasing stimulation intensity in both groups. Importantly, the increases in sympathetic and pressor responses to this fictive locomotion were significantly greater in SHR compared with WKY across all stimulation intensities (e.g., at 50 μA, ΔRSNA: WKY 153 ± 31%, SHR 287 ± 42%; ΔMAP: WKY 87 ± 9 mmHg, SHR 139 ± 7 mmHg). These findings provide the first evidence that central command may be a critical contributor to the exaggerated rise in sympathetic activity and blood pressure during exercise in hypertension. Copyright © 2016 the American Physiological Society.

  18. Role of stress system disturbance and enhanced novelty response in spatial learning of NCAM-deficient mice.

    PubMed

    Brandewiede, Joerg; Jakovcevski, Mira; Stork, Oliver; Schachner, Melitta

    2013-11-01

    The neural cell adhesion molecule (NCAM) plays a crucial role in stress-related brain function, emotional behavior and memory formation. In this study, we investigated the functions of the glucocorticoid and serotonergic systems in mice constitutively deficient for NCAM (NCAM-/- mice). Our data provide evidence for a hyperfunction of the hypothalamic-pituitary-adrenal axis, with enlarged adrenal glands and increased stress-induced corticosterone release, but reduced hippocampal glucocorticoid receptor expression in NCAM-/- mice when compared to NCAM+/+ mice. We also obtained evidence for a hypofunction of 5-HT1A autoreceptors as indicated by increased 8-0H-DPAT-induced hypothermia. These findings suggest a disturbance of both humoral and neural stress systems in NCAM-/- mice. Accordingly, we not only confirmed previously observed hyperarousal of NCAM-/- mice in various anxiety tests, but also observed an increased response to novelty exposure in these animals. Spatial learning deficits of the NCAM-/- mice in a Morris Water maze persisted, even when mice were pretrained to prevent effects of novelty or stress. We suggest that NCAM-mediated processes are involved in both novelty/stress-related emotional behavior and in cognitive function during spatial learning.

  19. Contagious risk taking: social information and context influence wild jackdaws’ responses to novelty and risk

    PubMed Central

    Greggor, Alison L.; McIvor, Guillam E.; Clayton, Nicola S.; Thornton, Alex

    2016-01-01

    Although wild animals increasingly encounter human-produced food and objects, it is unknown how they learn to discriminate beneficial from dangerous novelty. Since social learning allows animals to capitalize on the risk-taking of others, and avoid endangering themselves, social learning should be used around novel and unpredictable stimuli. However, it is unclear whether animals use social cues equally around all types of novelty and at all times of year. We assessed whether wild, individually marked jackdaws—a highly neophobic, yet adaptable species—are equally influenced by social cues to consume novel, palatable foods and to approach a startling object. We conducted these tests across two seasons, and found that in both seasons observers were more likely to consume novel foods after seeing a demonstrator do so. In contrast, observers only followed the demonstrator in foraging next to the object during breeding season. Throughout the year more birds were wary of consuming novel foods than wary of approaching the object, potentially leading to jackdaws’ greater reliance on social information about food. Jackdaws’ dynamic social cue usage demonstrates the importance of context in predicting how social information is used around novelty, and potentially indicates the conditions that facilitate animals’ adjustment to anthropogenic disturbance. PMID:27282438

  20. Contagious risk taking: social information and context influence wild jackdaws' responses to novelty and risk.

    PubMed

    Greggor, Alison L; McIvor, Guillam E; Clayton, Nicola S; Thornton, Alex

    2016-06-10

    Although wild animals increasingly encounter human-produced food and objects, it is unknown how they learn to discriminate beneficial from dangerous novelty. Since social learning allows animals to capitalize on the risk-taking of others, and avoid endangering themselves, social learning should be used around novel and unpredictable stimuli. However, it is unclear whether animals use social cues equally around all types of novelty and at all times of year. We assessed whether wild, individually marked jackdaws-a highly neophobic, yet adaptable species-are equally influenced by social cues to consume novel, palatable foods and to approach a startling object. We conducted these tests across two seasons, and found that in both seasons observers were more likely to consume novel foods after seeing a demonstrator do so. In contrast, observers only followed the demonstrator in foraging next to the object during breeding season. Throughout the year more birds were wary of consuming novel foods than wary of approaching the object, potentially leading to jackdaws' greater reliance on social information about food. Jackdaws' dynamic social cue usage demonstrates the importance of context in predicting how social information is used around novelty, and potentially indicates the conditions that facilitate animals' adjustment to anthropogenic disturbance.

  1. Does the age-related "anterior shift" of the P3 reflect an inability to habituate the novelty response?

    PubMed

    Alperin, Brittany R; Mott, Katherine K; Holcomb, Phillip J; Daffner, Kirk R

    2014-08-08

    Old adults often generate larger anterior neural responses than young adults when carrying out task requirements. A common finding in the ERP literature is an "anterior shift" of the P3b to targets. Utilizing principal component analysis (PCA), we recently demonstrated that rather than the P3b moving anteriorly, old adults generate a large P3a that temporally overlaps with their P3b. A dominant hypothesis for the age-related increase in anterior P3 is the failure to habituate the brain's novelty response to rare targets. We tested this hypothesis in young and old adults by comparing the amplitude of the PCA factor representing P3a to targets presented in the first versus last of eight blocks of a visual oddball task. If, unlike young adults, old adults are unable to habituate a novelty response, one would expect (1) the P3a amplitude to decrease between the first and last blocks for young, but not old subjects and (2) the difference in P3a amplitude between young and old subjects to be greater in the last than the first block. Our results indicate the amplitude of the P3a was larger in old adults than young adults. However, this effect was not modulated by block. These findings argue against the hypothesis that an age-related increase in the P3a to targets reflects an inability of old subjects to habituate a novelty response. An alternative hypothesis is that the augmented P3a indexes the increased utilization of frontal executive functions to provide compensatory scaffolding to carry out a task.

  2. Infants' ERP Responses to Novel and Familiar Stimuli Change over Time: Implications for Novelty Detection and Memory

    ERIC Educational Resources Information Center

    Wiebe, Sandra A.; Cheatham, Carol L.; Lukowski, Angela F.; Haight, Jennifer C.; Muehleck, Abigail J.; Bauer, Patricia J.

    2006-01-01

    Detection of novelty is an important cognitive ability early in development, when infants must learn a great deal about their world. Work with adults has identified networks of brain areas involved in novelty detection; this study investigated electro-physiological correlates of detection of novelty and recognition of familiarity in 9-month-old…

  3. Infants' ERP Responses to Novel and Familiar Stimuli Change over Time: Implications for Novelty Detection and Memory

    ERIC Educational Resources Information Center

    Wiebe, Sandra A.; Cheatham, Carol L.; Lukowski, Angela F.; Haight, Jennifer C.; Muehleck, Abigail J.; Bauer, Patricia J.

    2006-01-01

    Detection of novelty is an important cognitive ability early in development, when infants must learn a great deal about their world. Work with adults has identified networks of brain areas involved in novelty detection; this study investigated electro-physiological correlates of detection of novelty and recognition of familiarity in 9-month-old…

  4. Influence of Locomotor Muscle Metaboreceptor Stimulation on the Ventilatory Response to Exercise in Heart Failure

    PubMed Central

    Olson, Thomas P.; Joyner, Michael J.; Johnson, Bruce D.

    2010-01-01

    Background Whether locomotor muscle afferent neural activity contributes to exercise hyperpnea and symptoms of dyspnea in heart failure (HF) is controversial. We examined the influence of metaboreceptor stimulation on ventilation with and without maintaining end-exercise end-tidal CO2 levels. Methods and Results Eleven patients with HF aged 51±5 years (ejection fraction, 32±3%; New York Heart Association class, 1.6±0.2) and 11 age- and gender-matched healthy control participants aged 43±3 years were studied. Participants underwent 3 steady-state cycling sessions at 60% of peak oxygen consumption for 4 minutes. The first exercise session was a baseline control trial. Bilateral thigh tourniquets were inflated to suprasystolic pressure at end exercise for 2 minutes during 2 of the trials (regional circulatory occlusion) with the addition of inspired CO2 to maintain end-exercise partial pressure of end-tidal CO2 during 1 trial (regional circulatory occlusion+CO2). Minute ventilation was measured continuously throughout each trial. At 2 minutes postexercise during the baseline control trial in patients with HF, minute ventilation was 54% of end exercise, whereas the control group averaged 41% (P=0.11). During regional circulatory occlusion in patients with HF, minute ventilation was 60% of end exercise; however, the control group averaged 35% (P<0.001). During regional circulatory occlusion+CO2, the minute ventilation of patients with HF averaged 67% of end exercise, whereas the control group averaged 44% (P<0.001). Conclusion These data suggest that increased afferent neural activity from the large locomotor muscles associated with metabolites generated during exercise contribute to the augmented ventilatory response to exercise in patients with HF. PMID:20061520

  5. Cardiovascular responses to locomotor activity and feeding in unrestrained three-toed sloths, Bradypus variegatus.

    PubMed

    Duarte, D P F; Jaguaribe, A M; Pedrosa, M A C; Clementino, A C C R; Barbosa, A A; Silva, A F V; Gilmore, D P; Da Costa, C P

    2004-10-01

    Heart rate (HR) and systolic (SBP), diastolic (DBP) and mean (MBP) blood pressure were recorded by biotelemetry in nine conscious unrestrained sloths for 1 min every 15 min over a 24-h period. The animals were allowed to freely move in an acoustically isolated and temperature-controlled (24 +/- 1 degree C) experimental room with light-dark cycle (12/12 h). Behavior was closely monitored through a unidirectional visor and classified as resting (sitting or suspended), feeding (chewing and swallowing embauba leaves, Cecropia adenops), or locomotor activity around the tree trunk or on the room floor. Locomotor activity caused statistically significant increases in SBP (+8%, from 121 +/- 22 to 131 +/- 18 mmHg), DBP (+7%, from 86 +/- 17 to 92 +/- 10 mmHg), MBP (+8%, from 97 +/- 19 to 105 +/- 12 mmHg), and HR (+14%, from 84 +/- 15 to 96 +/- 15 bpm) compared to resting values, indicating a possible major influence of the autonomic nervous system on the modulation of cardiac function during this behavior. During feeding, the increase in blood pressure was even higher (SBP +27%, from 119 +/- 21 to 151 +/- 21 mmHg; DBP +21%, from 85 +/- 16 to 103 +/- 15 mmHg; MBP +24%, from 96 +/- 17 to 119 +/- 17 mmHg), while HR remained at 14% (from 84 +/- 15 to 96 +/- 10 bpm) above resting values. The proportionally greater increase in blood pressure than in HR during feeding suggests an increase in peripheral vascular resistance as part of the overall response to this behavior.

  6. Genetic Determinants of Target and Novelty Related Event-related Potentials in the Auditory Oddball Response

    PubMed Central

    Liu, Jingyu; Kiehl, Kent A.; Pearlson, Godfrey; Perrone-Bizzozero, Nora I.; Eichele, Tom; Calhoun, Vince D.

    2009-01-01

    Processing of novel and target stimuli in the auditory target detection or ‘oddball’ task encompasses the chronometry of perception, attention and working memory and is reflected in scalp recorded event-related potentials (ERPs). A variety of ERP components related to target and novelty processing have been described and extensively studied, and linked to deficits of cognitive processing. However, little is known about associations of genotypes with ERP endophenotypes. Here we sought to elucidate the genetic underpinnings of auditory oddball ERP components using a novel data analysis technique. A parallel independent component analysis of the electrophysiology and single nucleotide polymorphism (SNP) data was used to extract relations between patterns of ERP components and SNP associations purely based on an analysis incorporating higher order statistics. The method allows for broader associations of genotypes with phenotypes than traditional hypothesis-driven univariate correlational analyses. We show that target detection and processing of novel stimuli are both associated with a shared cluster of genes linked to the adrenergic and dopaminergic pathways. These results provide evidence of genetic influences on normal patterns of ERP generation during auditory target detection and novelty processing at the SNP association level. PMID:19285141

  7. Mechanism of an exaggerated locomotor response to a low-dose challenge of methamphetamine

    PubMed Central

    Frankel, Paul S.; Hoonakker, Amanda J.; Danaceau, Jonathan P.; Hanson, Glen R.

    2008-01-01

    Previous studies using phenylethylamine psychostimulants such as amphetamine (AMPH) have demonstrated that pretreatment with a high dose of drug followed by a low-dose challenge injection (3h later) results in an exaggerated behavioral response. In order to explore the mechanism of this exaggerated or what has been suggested to be a “sensitized” response, we investigated the effects of methamphetamine (METH) in a similar treatment paradigm. The current study found that, as suggested by previous studies, a low-dose challenge with METH substantially increased the locomotor response in animals that received a high-dose pretreatment (3.5 h prior to challenge). We also observed that rats displayed an increase in the concentrations of METH and its metabolite AMPH in the striatum following the low-dose challenge of METH if they were pretreated with METH versus saline. A similar pattern for METH and AMPH levels were measured in the plasma. Taken together, these results suggest that the accumulation of drug in animals pretreated with high-dose METH contributes to the overall enhanced behavioral response following challenges with low doses of METH. PMID:17303233

  8. Role of dopamine D1-like receptors in methamphetamine locomotor responses of D2 receptor knockout mice

    PubMed Central

    Kelly, M. A.; Low, M. J.; Rubinstein, M.; Phillips, T. J.

    2009-01-01

    Behavioral sensitization to psychostimulants manifests as an increased locomotor response with repeated administration. Dopamine systems are accepted to play a fundamental role in sensitization, but the role of specific dopamine receptor subtypes has not been completely defined. This study used the combination of dopamine D2 receptor-deficient mice and a D1-like antagonist to examine dopamine D1 and D2 receptor involvement in acute and sensitized locomotor responses to methamphetamine. Absence of the dopamine D2 receptor resulted in attenuation of the acute stimulant effects of methamphetamine. Mutant and wild-type mice exhibited sensitization that lasted longer within the time period of the challenge test in the mutant animals. Pretreatment with the D1-like receptor antagonist SCH 23390 produced more potent reductions in the acute and sensitized locomotor responses to methamphetamine in D2 receptor-deficient mice than in wild-type mice; however, the expression of locomotor sensitization when challenged with methamphetamine alone was equivalently attenuated by previous treatment with SCH 23390. These data suggest that dopamine D2 receptors play a key role in the acute stimulant and sensitizing effects of methamphetamine and act in concert with D1-like receptors to influence the acquisition of methamphetamine-induced behavioral sensitization, traits that may influence continued methamphetamine use. PMID:18363855

  9. Motor and locomotor responses to systemic amphetamine in three lines of selectively bred Long-Evans rats.

    PubMed

    Brudzynski, Stefan M; Gibson, Brittany; Silkstone, Michael; Burgdorf, Jeffrey; Kroes, Roger A; Moskal, Joseph R; Panksepp, Jaak

    2011-11-01

    The goal of the study was to measure spontaneous and amphetamine-induced motor and locomotor activity in three selectively bred lines of male Long-Evans rats. The number of 50 kHz ultrasonic vocalizations (USVs) emitted in response to heterospecific play with human hand ("tickling") had been measured daily in these lines of rats from 21 to 24 days of age, as a criterion for dividing them into high vocalizing line, low vocalizing line, and random breeding and testing lines. This study sought to determine whether selection of rats based on their affective social-vocalizations also had effects on their locomotor performance and sensitivity to amphetamine. In this study adult animals from the 25th generation (with no further selection) were tested. The results showed that rats, which were selectively bred to emit high numbers of 50 kHz vocalizations, also exhibited elevated levels of spontaneous locomotor activity. After systemic injection of d-amphetamine (1.5mg/kg), the level of motor and locomotor activity significantly increased further in all the lines as compared to saline controls. The horizontal and vertical activities and the distance covered by rats of the high line, both at the baseline and after amphetamine challenge, were significantly higher than those of the low line animals in absolute scores but not as proportion of relevant saline controls. Since appetitive 50 kHz USVs and locomotor activity are both dependent on the activity of the dopamine system, it is concluded that selection of rats based on the expression of their positive emotional state is also selecting other features than vocalization, namely locomotor behavior. This may help explain why these animals are relatively resistant to depressogenic manipulations.

  10. Comprehensive behavioral analysis of RNG105 (Caprin1) heterozygous mice: Reduced social interaction and attenuated response to novelty

    PubMed Central

    Ohashi, Rie; Takao, Keizo; Miyakawa, Tsuyoshi; Shiina, Nobuyuki

    2016-01-01

    RNG105 (also known as Caprin1) is a major RNA-binding protein in neuronal RNA granules, and is responsible for mRNA transport to dendrites and neuronal network formation. A recent study reported that a heterozygous mutation in the Rng105 gene was found in an autism spectrum disorder (ASD) patient, but it remains unclear whether there is a causal relation between RNG105 deficiency and ASD. Here, we subjected Rng105+/− mice to a comprehensive behavioral test battery, and revealed the influence of RNG105 deficiency on mouse behavior. Rng105+/− mice exhibited a reduced sociality in a home cage and a weak preference for social novelty. Consistently, the Rng105+/− mice also showed a weak preference for novel objects and novel place patterns. Furthermore, although the Rng105+/− mice exhibited normal memory acquisition, they tended to have relative difficulty in reversal learning in the spatial reference tasks. These findings suggest that the RNG105 heterozygous knockout leads to a reduction in sociality, response to novelty and flexibility in learning, which are implicated in ASD-like behavior. PMID:26865403

  11. Comprehensive behavioral analysis of RNG105 (Caprin1) heterozygous mice: Reduced social interaction and attenuated response to novelty.

    PubMed

    Ohashi, Rie; Takao, Keizo; Miyakawa, Tsuyoshi; Shiina, Nobuyuki

    2016-02-11

    RNG105 (also known as Caprin1) is a major RNA-binding protein in neuronal RNA granules, and is responsible for mRNA transport to dendrites and neuronal network formation. A recent study reported that a heterozygous mutation in the Rng105 gene was found in an autism spectrum disorder (ASD) patient, but it remains unclear whether there is a causal relation between RNG105 deficiency and ASD. Here, we subjected Rng105(+/-) mice to a comprehensive behavioral test battery, and revealed the influence of RNG105 deficiency on mouse behavior. Rng105(+/-) mice exhibited a reduced sociality in a home cage and a weak preference for social novelty. Consistently, the Rng105(+/-) mice also showed a weak preference for novel objects and novel place patterns. Furthermore, although the Rng105(+/-) mice exhibited normal memory acquisition, they tended to have relative difficulty in reversal learning in the spatial reference tasks. These findings suggest that the RNG105 heterozygous knockout leads to a reduction in sociality, response to novelty and flexibility in learning, which are implicated in ASD-like behavior.

  12. Responses to Novelty and Vulnerability to Cocaine Addiction: Contribution of a Multi-Symptomatic Animal Model

    PubMed Central

    Belin, David; Deroche-Gamonet, Véronique

    2012-01-01

    Epidemiological studies have revealed striking associations between several distinct behavioral/personality traits and drug addiction, with a large emphasis on the sensation-seeking trait and the associated impulsive dimension of personality. However, in human studies, it is difficult to identify whether personality/behavioral traits actually contribute to increased vulnerability to drug addiction or reflect psychobiological adaptations to chronic drug exposure. Here we show how animal models, including the first multi-symptomatic model of addiction in the rat, have contributed to a better understanding of the relationships between different subdimensions of the sensation-seeking trait and different stages of the development of cocaine addiction, from vulnerability to initiation of cocaine self-administration to the transition to compulsive drug intake. We argue that sensation seeking predicts vulnerability to use cocaine, whereas novelty seeking, akin to high impulsivity, predicts instead vulnerability to shift from controlled to compulsive cocaine use, that is, addiction. PMID:23125204

  13. Behavioral responses to novelty and structural variation of the hippocampus in mice. II. Multivariate genetic analysis.

    PubMed

    Crusio, W E; Schwegler, H; van Abeelen, J H

    1989-02-01

    On the basis of results from lesion studies in rodents, covariations are expected to exist between naturally-occurring heritable variations in hippocampal morphology and exploratory behavior elicited by novel surroundings. For this reason, we set up a full diallel cross between five inbred mouse strains and analyzed the behavioral and the hippocampal anatomical variation in male animals from this cross. Employing a bivariate extension of the diallel-cross analysis, estimates were obtained for the phenotypical, environmental, and genetical correlations between the phenotypes studied. A factor analysis performed on the matrix of additive-genetic correlations revealed that variations in the size of the intra- and infrapyramidal mossy fiber terminal fields (iip-MF) are negatively related to open-field exploration and novelty-induced fear. These results indicate that having larger iip-MF projections promotes the collection and processing of information about a novel environment, entailing lower levels of exploration and fear.

  14. Low and High Locomotor Responsiveness to Cocaine Predicts Intravenous Cocaine Conditioned Place Preference in Male Sprague-Dawley Rats

    PubMed Central

    Allen, Richard M.; Everett, Carson V.; Nelson, Anna M.; Gulley, Joshua M.; Zahniser, Nancy R.

    2009-01-01

    Outbred, male Sprague-Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on cocaine-induced locomotor activity in an open-field arena. This difference reflects cocaine’s ability to inhibit the striatal dopamine transporter and predicts development of sensitization. To investigate the relationship between initial cocaine locomotor responsiveness and cocaine reward, here we first classified rats as either LCRs or HCRs in a conditioned place preference (CPP) apparatus. Subsequently, we conducted cocaine conditioning trials, twice daily over four days with vehicle and cocaine (10 mg/kg, i.p. or 1 mg/kg, i.v.). When cocaine was administered by the i.p. route, similar to previous findings in the open-field, LCRs and HCRs were readily classified and locomotor sensitization developed in LCRs, but not HCRs. However, cocaine CPP was not observed. In contrast, when cocaine was administered by the i.v. route, the LCR/HCR classification not only predicted sensitization, but also CPP, with only LCR rats exhibiting sensitization and cocaine conditioning. Our findings show that the initial locomotor response to cocaine can predict CPP in male Sprague-Dawley rats under conditions when place conditioning develops, and that LCRs may be more prone to develop conditioning in the context of cocaine reward. PMID:17250883

  15. Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

    SciTech Connect

    Thanos, P.K.; Thanos, P.K.; Bermeo, C.; Rubinstein, M.; Suchland, K.L.; Wang, G.-J.; Grandy, D.K.; Volkow, N.D.

    2010-05-01

    Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs

  16. Reduced anticipatory locomotor responses to scheduled meals in ghrelin receptor deficient mice.

    PubMed

    Blum, I D; Patterson, Z; Khazall, R; Lamont, E W; Sleeman, M W; Horvath, T L; Abizaid, A

    2009-12-01

    Ghrelin, an orexigenic hormone produced by the stomach, is secreted in anticipation of scheduled meals and in correlation with anticipatory locomotor activity. We hypothesized that ghrelin is directly implicated in stimulating locomotor activity in anticipation of scheduled meals. To test this hypothesis, we observed 24 h patterns of locomotor activity in mice with targeted mutations of the ghrelin receptor gene (GHSR KO) and wild-type littermates, all given access to food for 4 h daily for 14 days. While wild type (WT) and GHSR KO mice produced increases in anticipatory locomotor activity, anticipatory locomotor activity in GHSR KO mice was attenuated (P<0.05). These behavioral measures correlated with attenuated levels of Fos immunoreactivity in a number of hypothalamic nuclei from GHSR KO placed on the same restricted feeding schedule for 7 days and sacrificed at ZT4. Interestingly, seven daily i.p. ghrelin injections mimicked hypothalamic Fos expression patterns to those seen in mice under restricted feeding schedules. These data suggest that ghrelin acts in the hypothalamus to augment locomotor activity in anticipation of scheduled meals.

  17. Reduced Anticipatory Locomotor Responses to Scheduled Meals in Ghrelin Receptor Deficient Mice

    PubMed Central

    Blum, Ian D.; Patterson, Zack; Khazall, Rim; Lamont, Elaine Waddington; Sleeman, Mark W.; Horvath, Tamas L.; Abizaid, Alfonso

    2009-01-01

    Ghrelin, an orexigenic hormone produced by the stomach, is secreted in anticipation of scheduled meals and in correlation with anticipatory locomotor activity. We hypothesized that ghrelin is directly implicated in stimulating locomotor activity in anticipation of scheduled meals. To test this hypothesis, we observed 24 hr patterns of locomotor activity in mice with targeted mutations of the ghrelin receptor gene (GHSR KO) and wild-type littermates, all given access to food for four hours daily for 14 days. While WT and GHSR KO mice produced increases in anticipatory locomotor activity, anticipatory locomotor activity in GHSR KO mice was attenuated (p.< 0.05). These behavioral measures correlated with attenuated levels of Fos immunoreactivity in a number of hypothalamic nuclei from GHSR KO placed on the same restricted feeding schedule for seven days and sacrificed at ZT4. Interestingly, seven daily intraperitoeneal ghrelin injections mimicked hypothalamic Fos expression patterns to those seen in mice under restricted feeding schedules. These data suggest that ghrelin acts in the hypothalamus to augment locomotor activity in anticipation of scheduled meals. PMID:19666088

  18. Dose-dependent changes in the locomotor responses to methamphetamine in BALB/c mice: low doses induce hypolocomotion.

    PubMed

    Singh, Rana A K; Kosten, Therese A; Kinsey, Berma M; Shen, Xiaoyun; Lopez, Angel Y; Kosten, Thomas R; Orson, Frank M

    2012-12-01

    The overall goal of the present study was to determine the effects of different doses of (+)-methamphetamine (meth) on locomotor activity of Balb/C mice. Four experiments were designed to test a wide range of meth doses in BALB/c female mice. In Experiment 1, we examined locomotor activity induced by an acute administration of low doses of meth (0.01 and 0.03mg/kg) in a 90-min session. Experiment 2 was conducted to test higher meth doses (0.3-10mg/kg). In Experiment 3, separate sets of mice were pre-treated with various meth doses once or twice (one injection/week) prior to a locomotor challenge with a low meth dose. Finally, in Experiment 4, we tested whether locomotor activation would be affected by pretreatment with a low or moderate dose of meth one month prior to the low meth dose challenge. Results show that low doses of meth induce hypolocomotion whereas moderate to high doses induce hyperlocomotion. Prior exposure to either one moderate or high dose of meth or to two, low doses of meth attenuated the hypolocomotor effect of a low meth dose one week later. This effect was also attenuated in mice tested one month after administration of a moderate meth dose. These results show that low and high doses of meth can have opposing effects on locomotor activity. Further, prior exposure to the drug leads to tolerance, rather than sensitization, of the hypolocomotor response to low meth doses. Published by Elsevier Inc.

  19. Fast and delayed locomotor response to acute high-dose nicotine administration in adult male rats.

    PubMed

    Jandová, K; Marešová, D; Pokorný, J

    2013-01-01

    The aim of the present study was to compare the immediate and delayed locomotor response to high-dose nicotine (NIC) administration in rats. The vertical and horizontal activity of behavior in adult male rats exposed to 1 mg/kg NIC or saline (SAL) were tested in a Laboras apparatus for one hour after drug application. Animals were then returned to their cages and housed for another seven days. After this period all animals were placed in Laboras again and their behavioral pattern was retested for another period of one hour (delayed response). Horizontal activity: immediately after nicotine administration animal were less mobile (first 2-minutes interval), when compared with controls. The immobilization effect of nicotine disappeared within 4 minutes and during whole first 10-minutes interval time spent by locomotion did not differ from controls. Locomotion activity of animals treated with nicotine increased robustly in following 10 minutes and remained significantly higher in 2nd, 3rd and 5th 10-minutes interval. Vertical activity: Rearing frequency was significantly lowered by NIC administration in first two minutes of the experiment and the same was found when the duration of rearing was analyzed. Lower rearing intensity of NIC treated animals disappeared in 4 minutes and was finally higher during whole test session as compared with controls. When duration of rearing was analyzed it was significantly longer in NIC treated animals. In majority of observed behavioral aspects there were no differences between NIC treated rats and controls seven days after NIC or SAL treatment. Our results reflect effect of NIC and we conclude that NIC significantly influences behavior of experimental animals.

  20. Effects of fentanyl administration on locomotor response in horses with the G57C μ-opioid receptor polymorphism.

    PubMed

    Wetmore, Lois A; Pascoe, Peter J; Shilo-Benjamini, Yael; Lindsey, Jane C

    2016-08-01

    OBJECTIVE To determine the locomotor response to the administration of fentanyl in horses with and without the G57C polymorphism of the μ-opioid receptor. ANIMALS 20 horses of various breeds and ages (10 horses heterozygous for the G57C polymorphism and 10 age-, breed-, and sex-matched horses that did not have the G57C polymorphism). PROCEDURES The number of steps each horse took was counted over consecutive 2-minute periods for 20 minutes to determine a baseline value. The horse then received a bolus of fentanyl (20 μg/kg, IV), and the number of steps was again counted during consecutive 2-minute periods for 60 minutes. The mean baseline value was subtracted from each 2-minute period after fentanyl administration; step counts with negative values were assigned a value of 0. Data were analyzed by use of a repeated-measures ANOVA. RESULTS Data for 19 of 20 horses (10 horses with the G57C polymorphism and 9 control horses without the G57C polymorphism) were included in the analysis. Horses with the G57C polymorphism had a significant increase in locomotor activity, compared with results for horses without the polymorphism. There was a significant group-by-time interaction. CONCLUSIONS AND CLINICAL RELEVANCE Horses heterozygous for the G57C polymorphism of the μ-opioid receptor had an increased locomotor response to fentanyl administration, compared with the response for horses without this polymorphism. The clinical impact of this finding should be investigated.

  1. Hemodynamic Response of the Supplementary Motor Area during Locomotor Tasks with Upright versus Horizontal Postures in Humans

    PubMed Central

    Obayashi, Shigeru; Nakajima, Katsumi; Hara, Yukihiro

    2016-01-01

    To understand cortical mechanisms related to truncal posture control during human locomotion, we investigated hemodynamic responses in the supplementary motor area (SMA) with quadrupedal and bipedal gaits using functional near-infrared spectroscopy in 10 healthy adults. The subjects performed three locomotor tasks where the degree of postural instability varied biomechanically, namely, hand-knee quadrupedal crawling (HKQuad task), upright quadrupedalism using bilateral Lofstrand crutches (UpQuad task), and typical upright bipedalism (UpBi task), on a treadmill. We measured the concentration of oxygenated hemoglobin (oxy-Hb) during the tasks. The oxy-Hb significantly decreased in the SMA during the HKQuad task, whereas it increased during the UpQuad task. No significant responses were observed during the UpBi task. Based on the degree of oxy-Hb responses, we ranked these locomotor tasks as UpQuad > UpBi > HKQuad. The order of the different tasks did not correspond with postural instability of the tasks. However, qualitative inspection of oxy-Hb time courses showed that oxy-Hb waveform patterns differed between upright posture tasks (peak-plateau-trough pattern for the UpQuad and UpBi tasks) and horizontal posture task (downhill pattern for the HKQuad task). Thus, the SMA may contribute to the control of truncal posture accompanying locomotor movements in humans. PMID:27413555

  2. Different locomotor sensitization responses to repeated cocaine injections are associated with differential phosphorylation of GluA1 in the dorsomedial striatum of adult rats.

    PubMed

    Kim, Myonghwan; Kim, Wonju; Baik, Ja-Hyun; Yoon, Bong-June

    2013-11-15

    Behavioral sensitization to psychostimulants reflects neural adaptation, which might share a common mechanism with drug addiction. Outbred male rats show different locomotor sensitization responses to cocaine, and cocaine also produces varied addictive progress in humans. We investigated whether differences in the induction of sensitization would affect the long-term persistence of sensitized locomotor activity, and we sought to determine the molecular basis for the variability in sensitization. Male Sprague-Dawley rats that showed sensitized locomotor responses over 5 consecutive daily cocaine injections (SENS) had significantly lower initial locomotor responses to the 1st cocaine exposure than did rats that did not show locomotor sensitization (NONS). Furthermore, rats that underwent 1 month of cocaine withdrawal after 5 repeated cocaine injections also exhibited sensitized or non-sensitized locomotor responses to a challenge injection of cocaine (SENS-C or NONS-C, respectively). This variability was also related to the initial responsiveness to cocaine. We examined the level of phosphorylation of the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropioniate receptor (AMPAR) in the dorsal striatum and found that there were significant differences between the sensitized rats and the non-sensitized rats. pGluA1-Ser831 was increased in the SENS rats during the induction of locomotor sensitization, and pGluA1-Ser845 was increased in the SENS-C rats during the expression of locomotor sensitization. These phosphorylation changes were observed in the dorsomedial striatum (DMS) of adult rats but not in the dorsolateral striatum (DLS) of adults. Our findings suggest that differential phosphorylation of AMPAR might be an important mechanism that contributes to the development of locomotor sensitization to cocaine in adult rats.

  3. Dynamics of goat distal hind limb muscle–tendon function in response to locomotor grade

    PubMed Central

    McGuigan, M. Polly; Yoo, Edwin; Lee, David V.; Biewener, Andrew A.

    2009-01-01

    Summary The functional roles of the lateral gastrocnemius (LG), medial gastrocnemius (MG) and superficial digital flexor (SDF) muscle–tendon units (MTUs) in domestic goats (N=6) were studied as a function of locomotor grade, testing the hypothesis that changes in distal limb muscle work would reflect changes in mechanical work requirements while goats walked or trotted on the level, 15 deg. decline and 15 deg. incline. As steep terrain-adapted animals, changes in muscle work output are expected to be particularly important for goats. In vivo muscle–tendon forces, fascicle length changes and muscle activation were recorded via tendon force buckles, sonomicrometry and electromyography to evaluate the work performance and elastic energy recovery of the three distal MTUs. These recordings confirmed that fascicle strain and force within goat distal hind limb muscles are adjusted in response to changes in mechanical work demand associated with locomotor grade. In general, muscle work was modulated most consistently by changes in fascicle strain, with increased net shortening (P<0.001) observed as goats switched from decline to level to incline locomotion. Peak muscle stresses increased as goats increased speed from a walk to a trot within each grade condition (P<0.05), and also increased significantly with grade (P<0.05 to P<0.01). Due to the increase in net fascicle shortening and muscle force, net muscle work per cycle also increased significantly (P<0.05 to P<0.005) as goats switched from decline to level to incline conditions (LG work: 20 mJ to 56 mJ to 209 mJ; MG work: –7 mJ to 34 mJ to 179 mJ; SDF work: –42 mJ to 14 mJ to 71 mJ, at a 2.5 ms–1 trot). Although muscle work was modulated in response to changes in grade, the amount of work produced by these three distal pennate muscles was small (being <3%) in comparison with the change in mechanical energy required of the limb as a whole. Elastic energy recovery in the SDF and gastrocnemius (GA) tendons was

  4. Adaptability: Conceptual and Empirical Perspectives on Responses to Change, Novelty and Uncertainty

    ERIC Educational Resources Information Center

    Martin, Andrew J.; Nejad, Harry; Colmar, Susan; Liem, Gregory Arief D.

    2012-01-01

    Adaptability is proposed as individuals' capacity to constructively regulate psycho-behavioral functions in response to new, changing, and/or uncertain circumstances, conditions and situations. The present investigation explored the internal and external validity of an hypothesised adaptability scale. The sample comprised 2,731 high school…

  5. Adaptability: Conceptual and Empirical Perspectives on Responses to Change, Novelty and Uncertainty

    ERIC Educational Resources Information Center

    Martin, Andrew J.; Nejad, Harry; Colmar, Susan; Liem, Gregory Arief D.

    2012-01-01

    Adaptability is proposed as individuals' capacity to constructively regulate psycho-behavioral functions in response to new, changing, and/or uncertain circumstances, conditions and situations. The present investigation explored the internal and external validity of an hypothesised adaptability scale. The sample comprised 2,731 high school…

  6. Loss of cocaine locomotor response in Pitx3-deficient mice lacking a nigrostriatal pathway.

    PubMed

    Beeler, Jeff A; Cao, Zhen Fang Huang; Kheirbek, Mazen A; Zhuang, Xiaoxi

    2009-04-01

    Both the dorsal and ventral striatum have been demonstrated to have a critical role in reinforcement learning and addiction. Dissecting the specific function of these striatal compartments and their associated nigrostriatal and mesoaccumbens dopamine pathways, however, has proved difficult. Previous studies using lesions to isolate the contribution of nigrostriatal and mesoaccumbens dopamine in mediating the locomotor and reinforcing effects of psychostimulant drugs have yielded inconsistent and inconclusive results. Using a naturally occurring mutant mouse line, aphakia, that lacks a nigrostriatal dopamine pathway but retains an intact mesoaccumbens pathway, we show that the locomotor activating effects of cocaine, including locomotor sensitization, are dependent on an intact nigrostriatal dopamine projection. In contrast, cocaine reinforcement, as measured by conditioned place preference and cocaine sensitization of sucrose preference, is intact in these mice. In light of the well-established role of the nucleus accumbens in mediating the effects of psychostimulants, these data suggest that the nigrostriatal pathway can act as a critical effector mechanism for the nucleus accumbens highlighting the importance of intrastriatal connectivity and providing insight into the functional architecture of the striatum.

  7. Novelty's effect on memory encoding.

    PubMed

    Rangel-Gomez, Mauricio; Janenaite, Sigita; Meeter, Martijn

    2015-07-01

    It is often thought that novelty benefits memory formation. However, support for this idea mostly comes from paradigms that are open to alternative explanations. In the present study we manipulated novelty in a word-learning task through task-irrelevant background images. These background images were either standard (presented repeatedly), or novel (presented only once). Two types of background images were used: Landscape pictures and fractals. EEG was also recorded during encoding. Contrary to the idea that novelty aids memory formation, memory performance was not affected by the novelty of the background. In the evoked response potentials, we found evidence of distracting effects of novelty: both the N1 and P3b components were smaller to words studied with novel backgrounds, and the amplitude of the N2b component correlated negatively with subsequent retrieval. We conclude that although evidence from other studies does suggest benefits on a longer time scale, novelty has no instantaneous benefits for learning. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Reinstating the Novelty P3

    PubMed Central

    Barry, Robert J.; Steiner, Genevieve Z.; De Blasio, Frances M.

    2016-01-01

    P300 (or P3) is a major positive complex in the human event-related potential, occurring some 300 ms after stimulus onset, and long thought to be the cortical correlate of the Orienting Reflex, our automatic attention-grabbing response to a novel stimulus. The Novelty P3 was the third P3 subcomponent discovered (after P3a and P3b) and appeared promising in its sensitivity to stimulus novelty, the defining characteristic of the Orienting Reflex. But some 15 years later it was claimed to be indistinguishable from the previously-discovered P3a. This led to a decline in interest in the field and confused nomenclature, with some studies using “P3a” and “Novelty P3” interchangeably. However, recent similar studies have again reported three subcomponents of the P3. Further, using single-stimulus habituation paradigms, in addition to P3a and P3b, a later decrementing P3 subcomponent has been reported, and recently labelled “HabP3” to avoid contention. We report three studies to resolve this chaotic situation, arguing for identification of the late subcomponent following the P3a and P3b as the Novelty P3. Reinstatement of the Novelty P3 as the central index of the Orienting Reflex will have widespread impact in a range of theoretical, practical, and clinical areas involving novelty processing and attention. PMID:27510599

  9. Reinstating the Novelty P3.

    PubMed

    Barry, Robert J; Steiner, Genevieve Z; De Blasio, Frances M

    2016-08-11

    P300 (or P3) is a major positive complex in the human event-related potential, occurring some 300 ms after stimulus onset, and long thought to be the cortical correlate of the Orienting Reflex, our automatic attention-grabbing response to a novel stimulus. The Novelty P3 was the third P3 subcomponent discovered (after P3a and P3b) and appeared promising in its sensitivity to stimulus novelty, the defining characteristic of the Orienting Reflex. But some 15 years later it was claimed to be indistinguishable from the previously-discovered P3a. This led to a decline in interest in the field and confused nomenclature, with some studies using "P3a" and "Novelty P3" interchangeably. However, recent similar studies have again reported three subcomponents of the P3. Further, using single-stimulus habituation paradigms, in addition to P3a and P3b, a later decrementing P3 subcomponent has been reported, and recently labelled "HabP3" to avoid contention. We report three studies to resolve this chaotic situation, arguing for identification of the late subcomponent following the P3a and P3b as the Novelty P3. Reinstatement of the Novelty P3 as the central index of the Orienting Reflex will have widespread impact in a range of theoretical, practical, and clinical areas involving novelty processing and attention.

  10. Nocturnal hyperactivity, increased social novelty preference and delayed extinction of fear responses in post-weaning socially isolated mice.

    PubMed

    Naert, Arne; Callaerts-Vegh, Zsuzsanna; D'Hooge, Rudi

    2011-07-15

    When rodents are reared in isolation from young age onwards, they manifest a number of behavioural alterations in adulthood. Since some of these alterations resemble symptoms of psychiatric disorders, the post-weaning social isolation (ISO) manipulation is often applied to create rodent models of these disorders. In rats, ISO effects have been thoroughly characterised, but in mice they are less well documented. Therefore, we further evaluated behaviour of adult ISO mice with a test battery that focussed on abnormalities relevant to schizophrenia. We found that ISO mice were hyperactive during the dark phase. Also, ISO mice showed alterations in magnitude, habituation and prepulse-inhibition of the acoustic startle reflex, increased anxiety, increased social preference and changes in extinction of fear responses. We did not observe increased sensitivity to locomotor-activating effects of amphetamine. It is concluded that ISO of mice might serve as a useful model to test further hypotheses regarding pathogenesis occurring at specific developmental timeframes. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. ANTECEDENTS AND CONSEQUENCES OF DRUG ABUSE IN RATS SELECTIVELY BRED FOR HIGH AND LOW RESPONSE TO NOVELTY

    PubMed Central

    Flagel, Shelly B.; waselus, Maria; Clinton, Sarah M; Watson, Stanley J.; Akil, Huda

    2013-01-01

    Human genetic and epidemiological studies provide evidence that only a subset of individuals who experiment with potentially addictive drugs become addicts. What renders some individuals susceptible to addiction remains to be determined, but most would agree that there is no single trait underlying the disorder. However, there is evidence in humans that addiction liability has a genetic component, and that certain personality characteristics related to temperament (e.g. the sensation-seeking trait) are associated with individual differences in addiction liability. Consequently, we have used a selective breeding strategy based on locomotor response to a novel environment to generate two lines of rats with distinct behavioral characteristics. We have found that the resulting phenotypes differ on a number of neurobehavioral dimensions relevant to addiction. Relative to bred low-responder (bLR) rats, bred high-responder (bHR) rats exhibit increased exploratory behavior, are more impulsive, more aggressive, seek stimuli associated with rewards, and show a greater tendency to relapse. We therefore utilize this unique animal model to parse the genetic, neural and environmental factors that contribute to addiction liability. Our work shows that the glucocorticoid receptor (GR), dopaminergic molecules, and members of the fibroblast growth factor family are among the neurotransmitters and neuromodulators that play a role in both the initial susceptibility to addiction as well as the altered neural responses that follow chronic drug exposure. Moreover, our findings suggest that the hippocampus plays a major role in mediating vulnerability to addiction. It is hoped that this work will emphasize the importance of personalized treatment strategies and identify novel therapeutic targets for humans suffering from addictive disorders. PMID:23639434

  12. Antecedents and consequences of drug abuse in rats selectively bred for high and low response to novelty.

    PubMed

    Flagel, Shelly B; Waselus, Maria; Clinton, Sarah M; Watson, Stanley J; Akil, Huda

    2014-01-01

    Human genetic and epidemiological studies provide evidence that only a subset of individuals who experiment with potentially addictive drugs become addicts. What renders some individuals susceptible to addiction remains to be determined, but most would agree that there is no single trait underlying the disorder. However, there is evidence in humans that addiction liability has a genetic component, and that certain personality characteristics related to temperament (e.g. the sensation-seeking trait) are associated with individual differences in addiction liability. Consequently, we have used a selective breeding strategy based on locomotor response to a novel environment to generate two lines of rats with distinct behavioral characteristics. We have found that the resulting phenotypes differ on a number of neurobehavioral dimensions relevant to addiction. Relative to bred low-responder (bLR) rats, bred high-responder (bHR) rats exhibit increased exploratory behavior, are more impulsive, more aggressive, seek stimuli associated with rewards, and show a greater tendency to relapse. We therefore utilize this unique animal model to parse the genetic, neural and environmental factors that contribute to addiction liability. Our work shows that the glucocorticoid receptor (GR), dopaminergic molecules, and members of the fibroblast growth factor family are among the neurotransmitters and neuromodulators that play a role in both the initial susceptibility to addiction as well as the altered neural responses that follow chronic drug exposure. Moreover, our findings suggest that the hippocampus plays a major role in mediating vulnerability to addiction. It is hoped that this work will emphasize the importance of personalized treatment strategies and identify novel therapeutic targets for humans suffering from addictive disorders. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

  13. Modeling Novelty Habituation During Exploratory Activity in Drosophila

    PubMed Central

    Soibam, Benjamin; Shah, Shishir; Gunaratne, Gemunu H.; Roman, Gregg W.

    2013-01-01

    Habituation is a common form of non-associative learning in which the organism gradually decreases its response to repeated stimuli. The decrease in exploratory activity of many animal species during exposure to a novel open field arena is a widely studied habituation paradigm. However, a theoretical framework to quantify how the novelty of the arena is learned during habituation is currently missing. Drosophila melanogaster display a high mean absolute activity and a high probability for directional persistence when first introduced to a novel arena. Both measures decrease during habituation to the arena. Here, we propose a phenomenological model of habituation for Drosophila exploration based on two principles: Drosophila form a spatial representation of the arena edge as a set of connected local patches, and repeated exposure to these patches is essential for the habituation of the novelty. The level of exposure depends on the number of visitations and is quantified by a variable referred to as “coverage.” This model was tested by comparing predictions against the experimentally measured behavior of wild type Drosophila. The novelty habituation of wild type Canton-S depends on coverage and is specifically independent of the arena radius. Our model describes the time dependent locomotor activity, ΔD, of Canton-S using an experimentally established stochastic process Pn(ΔD) which depends on the coverage. The quantitative measures of exploration and habituation were further applied to three mutant genotypes. Consistent with a requirement for vision in novelty habituation, blind no receptor potential A7 mutants display a failure in the decay of probability for directional persistence and mean absolute activity. The rutabaga2080 habituation mutant also shows defects in these measures. The kurtz1 non-visual arrestin mutant demonstrates a rapid decay in these measures, implying reduced motivation. The model and the habituation measures offer a powerful framework

  14. An integrated view on the oxygenation responses to incremental exercise at the brain, the locomotor and respiratory muscles.

    PubMed

    Boone, Jan; Vandekerckhove, Kristof; Coomans, Ilse; Prieur, Fabrice; Bourgois, Jan G

    2016-12-01

    In the past two decades oxygenation responses to incremental ramp exercise, measured non-invasively by means of near-infrared spectroscopy at different locations in the body, have advanced the insights on the underpinning mechanisms of the whole-body pulmonary oxygen uptake ([Formula: see text]) response. In healthy subjects the complex oxygenation responses at the level of locomotor and respiratory muscles, and brain were simplified and quantified by the detection of breakpoints as a deviation in the ongoing response pattern as work rate increases. These breakpoints were located in a narrow intensity range between 75 and 90 % of the maximal [Formula: see text] and were closely related to traditionally determined thresholds in pulmonary gas exchange (respiratory compensation point), blood lactate measurements (maximal lactate steady state), and critical power. Therefore, it has been assumed that these breakpoints in the oxygenation patterns at different sites in the body might be equivalent and could, therefore, be used interchangeably. In the present review the typical oxygenation responses (at locomotor and respiratory muscle level, and cerebral level) are described and a possible framework is provided showing the physiological events that might link the breakpoints at different body sites with the thresholds determined from pulmonary gas exchange and blood lactate measurements. However, despite a possible physiological association, several arguments prevent the current practical application of these breakpoints measured at a single site as markers of exercise intensity making it highly questionable whether measurements of the oxygenation response at one single site can be used as a reflection of whole-body responses to different exercise intensities.

  15. Transcriptional Responses and Mechanisms of Copper-Induced Dysfunctional Locomotor Behavior in Zebrafish Embryos.

    PubMed

    Zhang, Ting; Xu, Lian; Wu, Jun-Jie; Wang, Wei-Min; Mei, Jie; Ma, Xu-Fa; Liu, Jing-Xia

    2015-11-01

    Copper-induced delayed hatching and dysfunctional movement had been reported previously, and unbalanced free copper was found in the body of humans with Alzheimer's disease and other neural diseases, but details of the underlying mechanisms are still unknown. In this study, zebrafish (Danio rerio) embryos exposed to over 3.9 μM of copper-exhibited delayed hatching and significantly dysfunctional movement. Using high-throughput in situ hybridization screening and by conducting an in-depth analysis of gene characterization in embryos exposed to copper, we found that copper caused neural crest defects from the initiation stage of neurogenesis, and embryos younger than the 70% epiboly stage were sensitive to copper toxicity. The myelination of Schwann cells, other than melanophores, cartilage, and neurons, was inhibited by copper during neurogenesis. In addition, axon guidance was blocked by copper. Downregulated cdx4-hox might have contributed to the neurogenesis-related defects. Moreover, copper inhibited the differentiation of muscle fibers and myotomes but not the specification of muscle progenitors. In summary, our data reveal a novel molecular mechanism for copper-inhibited locomotor behavior in embryos, in which copper blocks functional muscle fiber specification during myogenesis and inhibits the specification of axons and Schwann cell myelination during neurogenesis. A combination of these processes results in dysfunctional locomotor behavior in zebrafish embryos exposed to copper. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Irreversible blockade of monoamine oxidases reveals the critical role of 5-HT transmission in locomotor response induced by nicotine in mice.

    PubMed

    Villégier, Anne-Sophie; Salomon, Lucas; Blanc, Gérard; Godeheu, Gérard; Glowinski, Jacques; Tassin, Jean-Pol

    2006-09-01

    Although nicotine is generally considered as the main compound responsible for addictive properties of tobacco, some experimental data indicate that nicotine does not exhibit all the characteristics of other substances of misuse such as psychostimulants and opiates. For example, nicotine generally fails to induce locomotor response in mice and self-administration of nicotine is difficult to obtain in rats. We have shown recently that a pretreatment with mixed irreversible monoamine oxidase inhibitors (MAOIs), such as tranylcypromine, triggers a locomotor response to nicotine in mice and induces a robust self-administration of nicotine in rats. We show here that when mice were pretreated with enhancers of extracellular levels of noradrenaline, dopamine or serotonin (D-amphetamine, GBR12783 or para-chloro-amphetamine, respectively) and injected with nicotine (1 mg/kg), only those animals pretreated with para-chloro-amphetamine exhibited a specific locomotor response to nicotine. These data indicate a critical role of serotonin in nicotine-induced locomotor activity in mice. This was further confirmed in microdialysis experiments showing that nicotine induces an increase in extracellular serotonin levels in the ventral striatum in mice pretreated with tranylcypromine. This effect of nicotine on extracellular serotonin levels was absent in mice lacking the beta2-subunit of the nicotinic acetylcholine receptor. Our data suggest that mixed irreversible MAOIs contained in tobacco facilitate the effects of nicotine on serotonin release, thus allowing the locomotor and rewarding effects of nicotine.

  17. Computational classification of different wild-type zebrafish strains based on their variation in light-induced locomotor response.

    PubMed

    Gao, Yuan; Zhang, Gaonan; Jelfs, Beth; Carmer, Robert; Venkatraman, Prahatha; Ghadami, Mohammad; Brown, Skye A; Pang, Chi Pui; Leung, Yuk Fai; Chan, Rosa H M; Zhang, Mingzhi

    2016-02-01

    Zebrafish larvae display a rapid and characteristic swimming behaviour after abrupt light onset or offset. This light-induced locomotor response (LLR) has been widely used for behavioural research and drug screening. However, the locomotor responses have long been shown to be different between different wild-type (WT) strains. Thus, it is critical to define the differences in the WT LLR to facilitate accurate interpretation of behavioural data. In this investigation, we used support vector machine (SVM) models to classify LLR data collected from three WT strains: AB, TL and TLAB (a hybrid of AB and TL), during early embryogenesis, from 3 to 9 days post-fertilisation (dpf). We analysed both the complete dataset and a subset of the data during the first 30after light change. This initial period of activity is substantially driven by vision, and is also known as the visual motor response (VMR). The analyses have resulted in three major conclusions: First, the LLR is different between the three WT strains, and at different developmental stages. Second, the distinguishable information in the VMR is comparable to, if not better than, the full dataset for classification purposes. Third, the distinguishable information of WT strains in the light-onset response differs from that in the light-offset response. While the classification accuracies were higher for the light-offset than light-onset response when using the complete LLR dataset, a reverse trend was observed when using a shorter VMR dataset. Together, our results indicate that one should use caution when extrapolating interpretations of LLR/VMR obtained from one WT strain to another.

  18. Maternal Accuracy and Behavior in Anticipating Children's Responses to Novelty: Relations to Fearful Temperament and Implications for Anxiety Development

    ERIC Educational Resources Information Center

    Kiel, Elizabeth J.; Buss, Kristin A.

    2010-01-01

    Previous research has suggested that mothers' behaviors may serve as a mechanism in the development from toddler fearful temperament to childhood anxiety. The current study examined the maternal characteristic of accuracy in predicting toddlers' distress reactions to novelty in relation to temperament, parenting, and anxiety development.…

  19. Maternal Accuracy and Behavior in Anticipating Children's Responses to Novelty: Relations to Fearful Temperament and Implications for Anxiety Development

    ERIC Educational Resources Information Center

    Kiel, Elizabeth J.; Buss, Kristin A.

    2010-01-01

    Previous research has suggested that mothers' behaviors may serve as a mechanism in the development from toddler fearful temperament to childhood anxiety. The current study examined the maternal characteristic of accuracy in predicting toddlers' distress reactions to novelty in relation to temperament, parenting, and anxiety development.…

  20. Blunted Refeeding Response and Increased Locomotor Activity in Mice Lacking FoxO1 in Synapsin-Cre–Expressing Neurons

    PubMed Central

    Ren, Hongxia; Plum-Morschel, Leona; Gutierrez-Juarez, Roger; Lu, Taylor Y.; Kim-Muller, Ja Young; Heinrich, Garrett; Wardlaw, Sharon L.; Silver, Rae; Accili, Domenico

    2013-01-01

    Successful development of antiobesity agents requires detailed knowledge of neural pathways controlling body weight, eating behavior, and peripheral metabolism. Genetic ablation of FoxO1 in selected hypothalamic neurons decreases food intake, increases energy expenditure, and improves glucose homeostasis, highlighting the role of this gene in insulin and leptin signaling. However, little is known about potential effects of FoxO1 in other neurons. To address this question, we executed a broad-based neuronal ablation of FoxO1 using Synapsin promoter–driven Cre to delete floxed Foxo1 alleles. Lineage-tracing experiments showed that NPY/AgRP and POMC neurons were minimally affected by the knockout. Nonetheless, Syn-Cre-Foxo1 knockouts demonstrated a catabolic energy homeostatic phenotype with a blunted refeeding response, increased sensitivity to leptin and amino acid signaling, and increased locomotor activity, likely attributable to increased melanocortinergic tone. We confirmed these data in mice lacking the three Foxo genes. The effects on locomotor activity could be reversed by direct delivery of constitutively active FoxO1 to the mediobasal hypothalamus, but not to the suprachiasmatic nucleus. The data reveal that the integrative function of FoxO1 extends beyond the arcuate nucleus, suggesting that central nervous system inhibition of FoxO1 function can be leveraged to promote hormone sensitivity and prevent a positive energy balance. PMID:23835335

  1. Blunted refeeding response and increased locomotor activity in mice lacking FoxO1 in synapsin-Cre-expressing neurons.

    PubMed

    Ren, Hongxia; Plum-Morschel, Leona; Gutierrez-Juarez, Roger; Lu, Taylor Y; Kim-Muller, Ja Young; Heinrich, Garrett; Wardlaw, Sharon L; Silver, Rae; Accili, Domenico

    2013-10-01

    Successful development of antiobesity agents requires detailed knowledge of neural pathways controlling body weight, eating behavior, and peripheral metabolism. Genetic ablation of FoxO1 in selected hypothalamic neurons decreases food intake, increases energy expenditure, and improves glucose homeostasis, highlighting the role of this gene in insulin and leptin signaling. However, little is known about potential effects of FoxO1 in other neurons. To address this question, we executed a broad-based neuronal ablation of FoxO1 using Synapsin promoter-driven Cre to delete floxed Foxo1 alleles. Lineage-tracing experiments showed that NPY/AgRP and POMC neurons were minimally affected by the knockout. Nonetheless, Syn-Cre-Foxo1 knockouts demonstrated a catabolic energy homeostatic phenotype with a blunted refeeding response, increased sensitivity to leptin and amino acid signaling, and increased locomotor activity, likely attributable to increased melanocortinergic tone. We confirmed these data in mice lacking the three Foxo genes. The effects on locomotor activity could be reversed by direct delivery of constitutively active FoxO1 to the mediobasal hypothalamus, but not to the suprachiasmatic nucleus. The data reveal that the integrative function of FoxO1 extends beyond the arcuate nucleus, suggesting that central nervous system inhibition of FoxO1 function can be leveraged to promote hormone sensitivity and prevent a positive energy balance.

  2. Daily treadmill exercise attenuates cocaine cue-induced reinstatement and cocaine induced locomotor response but increases cocaine-primed reinstatement

    PubMed Central

    Thanos, Panayotis K.; Stamos, Joshua; Robison, Lisa S.; Heyman, Gary; Tucci, Andrew; Wang, Gene-Jack; Robinson, John K.; Anderson, Brenda J.; Volkow, Nora D.

    2013-01-01

    Exercise affects neuroplasticity and neurotransmission including dopamine (DA), which modulates drug-taking behavior. Previous research in rodents has shown that exercise may attenuate the rewarding effects of drugs of abuse. The present study examined the effects of high and low exercise on cocaine responses in male Wistar rats that had been trained to self-administer and were compared to a group of sedentary rats. High exercise rats (HE) ran daily on a treadmill for 2 h and low exercise (LE) ran daily for 1 h. After 6 weeks of this exercise regimen, rats were tested over 2 days for reinstatement (day 1: cue-induced reinstatement; day 2: cocaine-primed reinstatement). During cue-induced reinstatement, the sedentary rats showed the expected increase in active lever responses when compared to maintenance, whereas these increased responses were inhibited in the exercised rats (HE and LE). During cocaine-primed reinstatement, however, there was a significant increase in active lever presses when compared to maintenance only in the HE group. This data suggests that chronic exercise during abstinence attenuates the cue-induced reinstatement seen in the sedentary rats by 26% (LE) and 21% (HE). In contrast, only the high exercise rats exhibited sensitized cocaine-seeking behavior (active lever presses) following cocaine-primed reinstatement. Finally, while sedentary rats increased locomotor activity during cocaine-primed reinstatement over that seen with cocaine during maintenance, this was not observed in the exercised rats, suggesting that exercise may interfere with the sensitized locomotor response during cocaine reinstatement. PMID:23103403

  3. Stability and variability of locomotor responses of laboratory rodents. III. Effect of environmental factors and lack of catecholamine receptor correlates.

    PubMed

    Vetulani, J; Marona-Lewicka, D; Michaluk, J; Popik, P

    1988-01-01

    The exploratory locomotor activity of rats differs between groups, and the results suggest the involvement of a seasonal factor. The body weight and the state of satiety do not appear to influence the locomotor activity. The individual activities of rats are correlated in subsequent tests only if the period between the tests is not long. The foehn wind changes the locomotor activity in the second test, depending on the animals' experience. No correlation between the native locomotor activity and cortical and striatal binding sites for [3H]prazosin and [3H]spiroperidol was found.

  4. Different dosing regimens of repeated ketamine administration have opposite effects on novelty processing in rats.

    PubMed

    Schumacher, Anett; Sivanandan, Brindan; Tolledo, Edgor Cole; Woldegabriel, Jacob; Ito, Rutsuko

    2016-08-01

    Repeated exposure to sub-anesthetic doses of ketamine in rats has been shown to induce cognitive deficits, as well as behavioral changes akin to the negative symptoms of schizophrenia, giving much face validity to the use of ketamine administration as a pharmacological model of schizophrenia. This study sought to further characterize the behavioral effects of two different ketamine pre-treatment regimens, focusing primarily on the effects of repeated ketamine administration on novelty processing, a capacity that is disrupted in schizophrenia. Rats received 5 or 14 intra-peritoneal injections of 30mg/kg ketamine or saline across 5 or 7days, respectively. They were then tested in an associative mismatch detection task to examine their ability to detect novel configurations of familiar audio-visual sequences. Furthermore, rats underwent a sequential novel object and novel object location exploration task. Subsequently, rats were also tested on the delayed matching to place T-maze task, sucrose preference task and locomotor tests involving administering a challenge dose of amphetamine (AMPH). The high-dose ketamine pre-treatment regimen elicited impairments in mismatch detection and working memory. In contrast, the low-dose ketamine pre-treatment regimen improved performance of novelty detection. In addition, low-dose ketamine pre-treated rats showed locomotor sensitization following an AMPH challenge, while the high-dose ketamine pre-treated rats showed an attenuated locomotor response to AMPH, compared to control rats. These findings demonstrate that different regimens of repeated ketamine administration induce alterations in novelty processing in opposite directions, and that differential neural adaptations occurring in the mesolimbic dopamine system may underlie these effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Olfactory bulbectomy induces rapid and stable changes in basal and stress-induced locomotor activity, heart rate and body temperature responses in the home cage.

    PubMed

    Vinkers, C H; Breuer, M E; Westphal, K G C; Korte, S M; Oosting, R S; Olivier, B; Groenink, L

    2009-03-03

    Olfactory bulbectomy (OBX) in rats causes several behavioral and neurochemical changes. However, the extent and onset of physiological and behavioral changes induced after bulbectomy have been little examined. Male Sprague-Dawley rats received telemetric implants. Before and immediately after OBX surgery, basal and stress-induced heart rate, body temperature, and locomotor activity were measured in the home cage in sham (n=9) and OBX animals (n=11). Stress was induced using novel cage stress or witness stress. Bulbectomized animals differed physiologically and behaviorally from shams. Nocturnally, OBX animals were significantly more active compared with shams, had a higher core body temperature and displayed a decreased heart rate variability. During the light period, OBX animals had a significantly lower basal heart rate and a reduced heart rate variability. These effects became apparent 2-3 days after OBX surgery, and were stable over time. After witness stress, OBX animals showed smaller autonomic (body temperature and heart rate) responses compared with shams, but showed no difference in locomotor responses. In contrast, novel cage stress led to increased locomotor responses in OBX rats compared with sham rats, while no differences were found in autonomic responses. Removal of the olfactory bulbs results in rapid, stable and persistent changes in basal locomotor activity, body temperature, heart rate and heart rate variability. Although the sleep-wake cycle of these parameters is not altered, increases in circadian amplitude are apparent within 3 days after surgery. This indicates that physiological changes in the OBX rat are the immediate result of olfactory bulb removal. Further, stress responsivity in OBX rats depends on stressor intensity. Bulbectomized rats display smaller temperature and heart rate responses to less intense witness stress compared with sham rats. Increased locomotor responses to more intense novel cage stress are present in the home cage

  6. Application of the Copenhagen Soccer Test in high-level women players - locomotor activities, physiological response and sprint performance.

    PubMed

    Bendiksen, Mads; Pettersen, Svein Arne; Ingebrigtsen, Jørgen; Randers, Morten B; Brito, João; Mohr, Magni; Bangsbo, Jens; Krustrup, Peter

    2013-12-01

    We evaluated the physiological response, sprint performance and technical ability in various phases of the Copenhagen Soccer Test for Women (CSTw) and investigated whether the locomotor activities of the CSTw were comparable to competitive match-play (CM). Physiological measurements and physical/technical assessments were performed during CSTw for eleven Norwegian high-level women soccer players. The activity pattern during CSTw and CM was monitored using the ZXY tracking system. No differences were observed between CSTw and CM with regards to total distance covered (10093±94 and 9674±191m), high intensity running (1278±67 and 1193±115m) or sprinting (422±55 and 372±46m) (p>.05). During CSTw, average HR was 85±2%HRmax with 35±2% playing time >90%HRmax. Blood lactate increased (p<.05) from 1.4±0.3mM at rest to an average of 4.7±0.5mM during CSTw, with no changes during the test. Blood glucose was 5.4±0.3mM at rest and remained unaltered during CSTw. Sprint performance (2×20m) decreased (p<.05) by 3% during CSTw (8.19±0.06-8.47±0.10s). In conclusion, the locomotor activities during CSTw were comparable to that of high-level competitive match-play. The physiological demands of the CSTw were high, with no changes in heart rate, blood lactate or technical performance during the test, but a lowered sprint performance towards the end of the test.

  7. Effects of feeding schedule on locomotor activity rhythms and stress response in sea bream.

    PubMed

    Sánchez, J A; López-Olmeda, J F; Blanco-Vives, B; Sánchez-Vázquez, F J

    2009-08-04

    Feeding cycles entrain biological rhythms, which enable animals to anticipate feeding times and so maximize food utilization and welfare. In this article, the effect of mealtime was investigated in two groups of sea bream (Sparus aurata): one group received a single daily meal at random times during the light period (random daytime feeding, RDF), whereas the other group received the meal during the light period but at the same time (scheduled daytime feeding, SDF). All the fish showed diurnal behavior, although the SDF group showed a lower percentage of diurnalism (84.4% vs. 79.5% in RDF and SDF respectively) and developed food anticipatory activity some hours before the mealtime. In addition, the mean daily locomotor activity of the RDF group was significantly higher than that of the SDF group (3132 vs. 2654 counts/day, respectively). Although the mean weight differed between both groups on day 30 (115.7 g and 125.6 g in RDF and SDF respectively), these differences had disappeared by day 60. Plasma cortisol and glucose significantly differed in both groups (cortisol: 71.8 vs. 8.7 ng/ml, glucose: 53.7 vs. 43.8 mg/dl in RDF and SDF, respectively), whereas lactate did not differ significantly. The results obtained suggest that altering the feeding time (scheduled vs. random) affects the behavior and physiology of sea bream, indicating that a single daily feeding cycle (compared to random) is beneficial for fish welfare because they can prepare themselves for the forthcoming feed.

  8. The Nicotine-Evoked Locomotor Response: A Behavioral Paradigm for Toxicity Screening in Zebrafish (Danio rerio) Embryos and Eleutheroembryos Exposed to Methylmercury

    PubMed Central

    Mora-Zamorano, Francisco X.; Svoboda, Kurt R.; Carvan, Michael J.

    2016-01-01

    This study is an adaptation of the nicotine-evoked locomotor response (NLR) assay, which was originally utilized for phenotype-based neurotoxicity screening in zebrafish embryos. Zebrafish embryos do not exhibit spontaneous swimming until roughly 4 days post-fertilization (dpf), however, a robust swimming response can be induced as early as 36 hours post-fertilization (hpf) by means of acute nicotine exposure (30–240μM). Here, the NLR was tested as a tool for early detection of locomotor phenotypes in 36, 48 and 72 hpf mutant zebrafish embryos of the non-touch-responsive maco strain; this assay successfully discriminated mutant embryos from their non-mutant siblings. Then, methylmercury (MeHg) was used as a proof-of-concept neurotoxicant to test the effectiveness of the NLR assay as a screening tool in toxicology. The locomotor effects of MeHg were evaluated in 6 dpf wild type eleutheroembryos exposed to waterborne MeHg (0, 0.01, 0.03 and 0.1μM). Afterwards, the NLR assay was tested in 48 hpf embryos subjected to the same MeHg exposure regimes. Embryos exposed to 0.01 and 0.03μM of MeHg exhibited significant increases in locomotion in both scenarios. These findings suggest that similar locomotor phenotypes observed in free swimming fish can be detected as early as 48 hpf, when locomotion is induced with nicotine. PMID:27123921

  9. Young pigs exhibit differential exploratory behavior during novelty preference tasks in response to age, sex, and delay.

    PubMed

    Fleming, Stephen A; Dilger, Ryan N

    2017-03-15

    Novelty preference paradigms have been widely used to study recognition memory and its neural substrates. The piglet model continues to advance the study of neurodevelopment, and as such, tasks that use novelty preference will serve especially useful due to their translatable nature to humans. However, there has been little use of this behavioral paradigm in the pig, and previous studies using the novel object recognition paradigm in piglets have yielded inconsistent results. The current study was conducted to determine if piglets were capable of displaying a novelty preference. Herein a series of experiments were conducted using novel object recognition or location in 3- and 4-week-old piglets. In the novel object recognition task, piglets were able to discriminate between novel and sample objects after delays of 2min, 1h, 1 day, and 2 days (all P<0.039) at both ages. Performance was sex-dependent, as females could perform both 1- and 2-day delays (P<0.036) and males could perform the 2-day delay (P=0.008) but not the 1-day delay (P=0.347). Furthermore, 4-week-old piglets and females tended to exhibit greater exploratory behavior compared with males. Such performance did not extend to novel location recognition tasks, as piglets were only able to discriminate between novel and sample locations after a short delay (P>0.046). In conclusion, this study determined that piglets are able to perform the novel object and location recognition tasks at 3-to-4 weeks of age, however performance was dependent on sex, age, and delay.

  10. The effect of experimental epilepsy induced by injection of tetanus toxin into the amygdala of the rat on eating behaviour and response to novelty.

    PubMed

    Mellanby, J; Oliva, M; Peniket, A; Nicholls, B

    1999-04-01

    A minute dose of tetanus toxin injected into the amygdala of rats produced an apparently reversible epileptiform syndrome similar to that previously described after injection of the toxin into the hippocampus. During the active epilepsy the toxin-injected rats occasionally exhibited 'paroxysmal eating' and also sometimes ran round in circles attempting to bite their own tails. When presented with a novel but palatable food (chocolate buttons or harvest crunch) the toxin-injected rats showed less neophobia than their controls--they ate sooner and ate more. This was found both during the active epilepsy and several weeks later when they had recovered. A similar effect of amygdala injections was found in a second experiment, in which the effect was compared with that of toxin injection in the hippocampus. These rats were tested also on the playground maze on their approach response to a neutral novel object (in a familiar environment in the context of seven familiar objects). The amygdala rats did not show any increase in their novelty response; thus their reduction in neophobia was specific to an appetitive behaviour. In contrast, the hippocampally-injected rats did not exhibit a novelty response in the playground maze, but showed normal neophobia to a new food.

  11. Assessment of Postflight Locomotor Performance Utilizing a Test of Functional Mobility: Strategic and Adaptive Responses

    NASA Technical Reports Server (NTRS)

    Warren, L. E.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Ruttley, T. M.; Bloomberg, J. J.

    2006-01-01

    Space flight induces adaptive modification in sensorimotor function, allowing crewmembers to operate in the unique microgravity environment. This adaptive state, however, is inappropriate for a terrestrial environment. During a re-adaptation period upon their return to Earth, crewmembers experience alterations in sensorimotor function, causing various disturbances in perception, spatial orientation, posture, gait, and eye-head coordination. Following long duration space flight, sensorimotor dysfunction would prevent or extend the time required to make an emergency egress from the vehicle; compromising crew safety and mission objectives. We are investigating two types of motor learning that may interact with each other and influence a crewmember's ability to re-adapt to Earth's gravity environment. In strategic learning, crewmembers make rapid modifications in their motor control strategy emphasizing error reduction. This type of learning may be critical during the first minutes and hours after landing. In adaptive learning, long-term plastic transformations occur, involving morphological changes and synaptic modification. In recent literature these two behavioral components have been associated with separate brain structures that control the execution of motor strategies: the strategic component was linked to the posterior parietal cortex and the adaptive component was linked to the cerebellum (Pisella, et al. 2004). The goal of this paper was to demonstrate the relative contributions of the strategic and adaptive components to the re-adaptation process in locomotor control after long duration space flight missions on the International Space Station (ISS). The Functional Mobility Test (FMT) was developed to assess crewmember s ability to ambulate postflight from an operational and functional perspective. Sixteen crewmembers were tested preflight (3 sessions) and postflight (days 1, 2, 4, 7, 25) following a long duration space flight (approx 6 months) on the ISS. We

  12. Assessment of Postflight Locomotor Performance Utilizing a Test of Functional Mobility: Strategic and Adaptive Responses

    NASA Technical Reports Server (NTRS)

    Warren, L. E.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Ruttley, T. M.; Bloomberg, J. J.

    2006-01-01

    Space flight induces adaptive modification in sensorimotor function, allowing crewmembers to operate in the unique microgravity environment. This adaptive state, however, is inappropriate for a terrestrial environment. During a re-adaptation period upon their return to Earth, crewmembers experience alterations in sensorimotor function, causing various disturbances in perception, spatial orientation, posture, gait, and eye-head coordination. Following long duration space flight, sensorimotor dysfunction would prevent or extend the time required to make an emergency egress from the vehicle; compromising crew safety and mission objectives. We are investigating two types of motor learning that may interact with each other and influence a crewmember's ability to re-adapt to Earth's gravity environment. In strategic learning, crewmembers make rapid modifications in their motor control strategy emphasizing error reduction. This type of learning may be critical during the first minutes and hours after landing. In adaptive learning, long-term plastic transformations occur, involving morphological changes and synaptic modification. In recent literature these two behavioral components have been associated with separate brain structures that control the execution of motor strategies: the strategic component was linked to the posterior parietal cortex and the adaptive component was linked to the cerebellum (Pisella, et al. 2004). The goal of this paper was to demonstrate the relative contributions of the strategic and adaptive components to the re-adaptation process in locomotor control after long duration space flight missions on the International Space Station (ISS). The Functional Mobility Test (FMT) was developed to assess crewmember s ability to ambulate postflight from an operational and functional perspective. Sixteen crewmembers were tested preflight (3 sessions) and postflight (days 1, 2, 4, 7, 25) following a long duration space flight (approx 6 months) on the ISS. We

  13. Chronic cocaine or ethanol exposure during adolescence alters novelty-related behaviors in adulthood.

    PubMed

    Stansfield, Kirstie H; Kirstein, Cheryl L

    2007-04-01

    Adolescence is a time of high-risk behavior and increased exploration. This developmental period is marked by a greater probability to initiate drug use and is associated with an increased risk to develop addiction and adulthood dependency and drug use at this time is associated with an increased risk. Human adolescents are predisposed toward an increased likelihood of risk-taking behaviors [Zuckerman M. Sensation seeking and the endogenous deficit theory of drug abuse. NIDA Res Monogr 1986;74:59-70.], including drug use or initiation. In the present study, adolescent animals were exposed to twenty days of either saline (0.9% sodium chloride), cocaine (20 mg/kg) or ethanol (1 g/kg) i.p. followed by a fifteen-day washout period. All animals were tested as adults on several behavioral measures including locomotor activity induced by a novel environment, time spent in the center of an open field, novelty preference and novel object exploration. Animals exposed to cocaine during adolescence and tested as adults exhibited a greater locomotor response in a novel environment, spent less time in the center of the novel open field and spent less time with a novel object, results that are indicative of a stress or anxiogenic response to novelty or a novel situation. Adolescent animals chronically administered ethanol and tested as adults, unlike cocaine-exposed were not different from controls in a novel environment, indicated by locomotor activity or time spent with a novel object. However, ethanol-exposed animals approached the novel object more, suggesting that exposure to ethanol during development may result in less-inhibited behaviors during adulthood. The differences in adult behavioral responses after drug exposure during adolescence are likely due to differences in the mechanisms of action of the drugs and subsequent reward and/or stress responsivity. Future studies are needed to determine the neural substrates of these long lasting drug-induced changes.

  14. The potential anti-addictive agent, 18-methoxycoronaridine, blocks the sensitized locomotor and dopamine responses produced by repeated morphine treatment.

    PubMed

    Szumlinski, K K; Maisonneuve, I M; Glick, S D

    2000-05-02

    18-Methoxycoronaridine (18-MC), a novel synthetic iboga congener, attenuates the reinforcing efficacy of morphine, disrupts some signs of morphine withdrawal in physically dependent rats and attenuates the dopamine response in the nucleus accumbens to acute morphine. The present study further investigated the interactions between 18-MC and morphine by examining the effects of 18-MC (40 mg/kg, i.p., 19 h earlier) on the expression of dopamine sensitization in the nucleus accumbens in response to morphine (20 mg/kg, i.p.) and on the dose-effect curves for morphine-induced locomotion (0-30 mg/kg, i.p.) in rats treated either acutely or repeatedly (five, once daily, injections of 20 mg/kg, i.p.) with morphine. Compared to vehicle pretreated controls, 18-MC increased the potency of morphine, shifting the dose-response curve to the left, in acute morphine treated rats; however, 18-MC did not alter the potency of morphine in rats treated repeatedly with morphine. Repeated morphine administration induced locomotor sensitization in approximately 50% of the rats tested; in vehicle pretreated rats, the morphine dose-response curve was shifted to the left in sensitized as compared to non-sensitized rats. In 18-MC pretreated rats, sensitized and non-sensitized rats responded similarly to morphine, revealing a blockade of sensitization by 18-MC. Consistent with this behavioural finding, 18-MC pretreatment completely abolished the sensitized dopamine response in the nucleus accumbens expressed by rats repeatedly treated with morphine. It is suggested that the potential anti-addictive efficacy of 18-MC might be related to an ability to restore normal functioning to a hypersensitive mesolimbic dopamine system produced by previous repeated morphine administration.

  15. Maternal immune activation in late gestation enhances locomotor response to acute but not chronic amphetamine treatment in male mice offspring: role of the D1 receptor.

    PubMed

    Zager, Adriano; Mennecier, Gregory; Palermo-Neto, João

    2012-06-15

    Exposure to elevated levels of maternal cytokines can lead to functional abnormalities of the dopaminergic system in the adult offspring, including enhanced amphetamine (AMPH)-induced locomotion. Therefore, it seems reasonable to consider that offspring of challenged mothers would behave differently in models of addictive behavior, such as behavioral sensitization. Thus, we sought to evaluate the effects of prenatal exposure to lipopolysaccharide (LPS) on the locomotor response to acute and chronic AMPH treatment in male mice offspring. For this purpose, LPS (Escherichia coli 0127:B8; 120 μg/kg) was administered intraperitoneally to pregnant Swiss mice on gestational day 17. At adulthood, male offspring were studied under one of the following conditions: (1) locomotor response to acute AMPH treatment (2.5 or 5.0 mg/kg) in an open field test; (2) behavioral sensitization paradigm, which consists of a daily injection of AMPH (1.0 mg/kg) for 10 days and observation of locomotion in the open field on days 1, 5, 10 (development phase), 15 and 17 (expression phase). The LPS stimulated offspring showed enhancement of the locomotor-stimulant effect after an acute AMPH challenge in comparison to baseline and saline pre-treated mice. They also showed development of behavioral sensitization earlier than the saline pre-treated group, although no changes between saline and LPS pre-treated groups were observed on development or expression of locomotor behavioral sensitization to AMPH. Furthermore, there was up-regulation of D1 receptor protein level within striatum in the LPS-stimulated offspring which was strongly correlated with increased grooming behavior. Taken together, our results indicate that motor and dopaminergic alterations caused by maternal immune activation are restricted to the acute AMPH challenge, mostly due to up-regulation of the D1 receptor within the mesolimbic and nigrostriatal pathways, but no locomotor differences were observed for behavioral

  16. Novelty and Promotional Items

    EPA Pesticide Factsheets

    Small novelty or promotional products, primarily used for outreach and educational purposes, must effectively convey a message, and their purchase will only be allowed if the item will contribute to the accomplishment of the Agency's mission.

  17. Novelty or Surprise?

    PubMed Central

    Barto, Andrew; Mirolli, Marco; Baldassarre, Gianluca

    2013-01-01

    Novelty and surprise play significant roles in animal behavior and in attempts to understand the neural mechanisms underlying it. They also play important roles in technology, where detecting observations that are novel or surprising is central to many applications, such as medical diagnosis, text processing, surveillance, and security. Theories of motivation, particularly of intrinsic motivation, place novelty and surprise among the primary factors that arouse interest, motivate exploratory or avoidance behavior, and drive learning. In many of these studies, novelty and surprise are not distinguished from one another: the words are used more-or-less interchangeably. However, while undeniably closely related, novelty and surprise are very different. The purpose of this article is first to highlight the differences between novelty and surprise and to discuss how they are related by presenting an extensive review of mathematical and computational proposals related to them, and then to explore the implications of this for understanding behavioral and neuroscience data. We argue that opportunities for improved understanding of behavior and its neural basis are likely being missed by failing to distinguish between novelty and surprise. PMID:24376428

  18. Locomotor and behavioural responses of empire gudgeons (Hypseleotris compressa) exposed to coal mine wastewater.

    PubMed

    Lanctôt, C; Melvin, S D; Leusch, F D L; Wilson, S; Fabbro, L

    2016-02-01

    Coal mining generates large quantities of complex effluent and may pose a threat to aquatic wildlife. Despite this, few studies have explored the consequences of exposure to mine wastewater on aquatic organisms, and this is particularly true for the Australian environment. We investigated sub-lethal behavioural responses in a native Australian fish exposed to wastewater from two releasing dams (CMW1 and CMW2) located at an open cut coal mine in Central Queensland. Swimming activity and movement of empire gudgeons (Hypseleotris compressa) were assessed during a two-week exposure using video-tracking software. Increased activity was observed in exposed fish after 7 and 14 days. Specifically, we found a significant increase in the mean velocity and mobility of fish exposed to CMW1 treatments. Exposed fish also spent on average 23% more time in the peripheral zone compared to controls after 14-d exposures. A similar response pattern was observed in fish exposed to CMW2, but differences between treated and control fish did not generally reach statistical significance. Alterations to normal swimming activity and movement patterns can be indicative of a stress response in fish, and could subsequently lead to negative population-level impacts by increasing the conspicuousness of exposed individuals to predators, or by altering foraging abilities. More research is warranted to explore relationships between behavioural and physiological outcomes, including endocrine disruption, and subsequent population-level outcomes in aquatic organisms at risk of exposure to coal process-affected water. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Behavioral responses to novelty and structural variation of the hippocampus in mice. I. Quantitative-genetic analysis of behavior in the open-field.

    PubMed

    Crusio, W E; Schwegler, H; van Abeelen, J H

    1989-02-01

    As a first step towards a multivariate quantitative-genetic analysis of covariations between heritable variation in hippocampal structure and mouse behavior, a univariate analysis of the genetic architecture of behavioral responses to novelty is presented. For several components of exploratory behavior considerable amounts of genetic variation were found and an evolutionary history of stabilizing selection for intermediate levels of exploration was inferred. Comparison of these results with those from a previous study indicated that even a relatively small diallel cross, involving 4-5 inbred strains, may provide useful genetic information on a specific sample of animals. Larger numbers of strains are needed to provide precise estimates of genetic parameters in a population.

  20. Locomotor micro-activities associated with therapeutic responses in patients with seasonal affective disorders

    PubMed Central

    Ohashi, Kyoko; Yamamoto, Yoshiharu; Teicher, Martin H.

    2015-01-01

    Background Psychomotor retardation, leaden paralysis and fatigue are often used to describe patients with depressive disorders. However, there is limited understanding of their meaning and how they are objectively manifested in the physical world. Patients with seasonal affective disorder (SAD) are characteristically hypoactive, and experience restoration in energy during effective treatment with bright light. In this study, we attempt to identify quantitative metrics of psychomotor activity that correspond to the clinical perceptions of hypoactivity and to the early activating effects of treatment. Methods Novel means of assessing the microstructure of activity was employed using wavelets and Hurst exponents to indicate the proclivity of subjects to persist at higher and lower levels of activity. This was assesed using actigraphs in 16 unmedicated patients with SAD before and following two weeks of bright light therapy. Results Two weeks of phototherapy had no significant effect on mean levels of diurnal activity, but altered the microstructure of the activity. Specifically, phototherapy produced a significant reduction in inertial resistance in patients who had a 50% or greater reduction in Hamilton Depression scores (n=8), as reflected in reduced tendency to persist at low levels of activity. There was also a strong correlation between ratings of fatigue and measures of persistence at high versus low activity in initial responders, but not in initial non-responders. Conclusion These findings suggest that light therapy alters the nature of diurnal activity troughs in early responsive patients, reducing their tendency to persist at low levels, possibly reflecting an alleviation of psychomotor retardation. PMID:27135034

  1. Locomotor micro-activities associated with therapeutic responses in patients with seasonal affective disorders.

    PubMed

    Ohashi, Kyoko; Yamamoto, Yoshiharu; Teicher, Martin H

    2015-04-01

    Psychomotor retardation, leaden paralysis and fatigue are often used to describe patients with depressive disorders. However, there is limited understanding of their meaning and how they are objectively manifested in the physical world. Patients with seasonal affective disorder (SAD) are characteristically hypoactive, and experience restoration in energy during effective treatment with bright light. In this study, we attempt to identify quantitative metrics of psychomotor activity that correspond to the clinical perceptions of hypoactivity and to the early activating effects of treatment. Novel means of assessing the microstructure of activity was employed using wavelets and Hurst exponents to indicate the proclivity of subjects to persist at higher and lower levels of activity. This was assesed using actigraphs in 16 unmedicated patients with SAD before and following two weeks of bright light therapy. Two weeks of phototherapy had no significant effect on mean levels of diurnal activity, but altered the microstructure of the activity. Specifically, phototherapy produced a significant reduction in inertial resistance in patients who had a 50% or greater reduction in Hamilton Depression scores (n=8), as reflected in reduced tendency to persist at low levels of activity. There was also a strong correlation between ratings of fatigue and measures of persistence at high versus low activity in initial responders, but not in initial non-responders. These findings suggest that light therapy alters the nature of diurnal activity troughs in early responsive patients, reducing their tendency to persist at low levels, possibly reflecting an alleviation of psychomotor retardation.

  2. Central blockade of melanocortin receptors attenuates the metabolic and locomotor responses to peripheral interleukin-1beta administration.

    PubMed

    Whitaker, Keith W; Reyes, Teresa M

    2008-03-01

    Loss of appetite and cachexia is an obstacle in the treatment of chronic infection and cancer. Proinflammatory cytokines released from activated immune cells and acting in the central nervous system (CNS) are prime candidates for mediating these metabolic changes, potentially affecting both energy intake as well as energy expenditure. The effect of intravenous administration of two proinflammatory cytokines, interleukin (IL)-1beta (15 microg/kg) and tumor necrosis factor (TNF)-alpha (10 microg/kg), on food and water intake, locomotor activity, oxygen consumption (VO2), and respiratory exchange ratio (RER) was evaluated. The two cytokines elicited a comparable decrease in food intake and activated similar numbers of cells in the paraventricular nucleus of the hypothalamus (PVH), a region that plays a critical role in the regulation of appetite and metabolism (determined via expression of the immediate early gene, c-fos). However, only IL-1beta reduced locomotion and RER, and increased VO2, while TNF-alpha was without effect. To examine the role of the melanocortins in mediating IL-1beta- induced metabolic changes, animals were pretreated centrally with a melanocortin receptor antagonist, HS014. Pretreatment with HS014 blocked the effect of IL-1beta on food intake and RER at later time points (beyond 8 h post injection), as well as the hypoactivity and increased metabolic rate. Further, HS014 blocked the induction of Fos-ir in the PVH. These data highlight the importance of the melanocortin system, particularly within the PVH, in mediating a broad range of metabolic responses to IL-1beta.

  3. QTL and systems genetics analysis of mouse grooming and behavioral responses to novelty in an open field.

    PubMed

    Delprato, A; Algéo, M-P; Bonheur, B; Bubier, J A; Lu, L; Williams, R W; Chesler, E J; Crusio, W E

    2017-05-24

    The open field is a classic test used to assess exploratory behavior, anxiety and locomotor activity in rodents. Here, we mapped quantitative trait loci (QTLs) underlying behaviors displayed in an open field, using a panel of 53 BXD recombinant inbred mouse strains with deep replication (10 per strain and sex). The use of these strains permits the integration and comparison of data obtained in different laboratories, and also offers the possibility to study trait covariance by exploiting powerful bioinformatics tools and resources. We quantified behavioral traits during 20-min test sessions including (1) percent time spent and distance traveled near the wall (thigmotaxis), (2) leaning against the wall, (3) rearing, (4) jumping, (5) grooming duration, (6) grooming frequency, (7) locomotion and (8) defecation. All traits exhibit moderate heritability making them amenable to genetic analysis. We identified a significant QTL on chromosome M.m. 4 at approximately 104 Mb that modulates grooming duration in both males and females (likelihood ratio statistic values of approximately 18, explaining 25% and 14% of the variance, respectively) and a suggestive QTL modulating locomotion that maps to the same locus. Bioinformatic analysis indicates Disabled 1 (Dab1, a key protein in the reelin signaling pathway) as a particularly strong candidate gene modulating these behaviors. We also found 2 highly suggestive QTLs for a sex by strain interaction for grooming duration on chromosomes 13 and 17. In addition, we identified a pairwise epistatic interaction between loci on chromosomes 12 at 36-37 Mb and 14 at 34-36 Mb that influences rearing frequency in males. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  4. Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1A sequences.

    PubMed

    Li, Qian; Holmes, Andrew; Ma, Li; Van de Kar, Louis D; Garcia, Francisca; Murphy, Dennis L

    2004-12-01

    Our previous studies found that serotonin transporter (SERT) knock-out mice showed increased sensitivity to minor stress and increased anxiety-like behavior but reduced locomotor activity. These mice also showed decreased density of 5-hydroxytryptamine (5-HT1A) receptors in the hypothalamus, amygdala, and dorsal raphe. To evaluate the contribution of hypothalamic 5-HT1A receptors to these phenotypes of SERT knock-out mice, two studies were conducted. Recombinant adenoviruses containing 5-HT1A sense and antisense sequences (Ad-1AP-sense and Ad-1AP-antisense) were used to manipulate 5-HT1A receptors in the hypothalamus. The expression of the 5-HT1A genes is controlled by the 5-HT1A promoter, so that they are only expressed in 5-HT1A receptor-containing cells. (1) Injection of Ad-1AP-sense into the hypothalamus of SERT knock-out mice restored 5-HT1A receptors in the medial hypothalamus; this effect was accompanied by elimination of the exaggerated adrenocorticotropin responses to a saline injection (minor stress) and reduced locomotor activity but not by a change in increased exploratory anxiety-like behavior. (2) To further confirm the observation in SERT-/- mice, Ad-1AP-antisense was injected into the hypothalamus of normal mice. The density and the function of 5-HT1A receptors in the medial hypothalamus were significantly reduced in Ad-1AP-antisense-treated mice. Compared with the control group (injected with Ad-track), Ad-1A-antisense-treated mice showed a significant reduction in locomotor activity, but again no changes in exploratory anxiety-like behaviors, tested by elevated plus-maze and open-field tests. Thus, the present results demonstrate that medial hypothalamic 5-HT1A receptors regulate stress responses and locomotor activity but may not regulate exploratory anxiety-like behaviors.

  5. Novelty as a Reinforcer for Position Learning in Children

    ERIC Educational Resources Information Center

    Wilson, Marian Monyok

    1974-01-01

    The stimulus-familiarization-effect (SFE) paradigm, a reaction-time (RT) task based on a response to novelty procedure, was modified to assess response for novelty, ie., a response-reinforcement sequence. The potential implications of attention for reinforcement theory and learning in general are discussed. (Author/CS)

  6. Novel technology for modulating locomotor activity as an operant response in the mouse: implications for neuroscience studies involving "exercise" in rodents.

    PubMed

    Fantegrossi, William E; Xiao, Wendy R; Zimmerman, Sarah M

    2013-01-30

    We have developed a novel, low-cost device designed to monitor and modulate locomotor activity in murine subjects. This technology has immediate application to the study of effects of physical exercise on various neurobiological endpoints, and will also likely be useful in the study of psychomotor sensitization and drug addiction. Here we demonstrate the capacity of these devices to establish locomotor activity as an operant response reinforced by food pellet presentations, and show that schedules of reinforcement can reliably control this behavior. Importantly, these data show that varying degrees of increased locomotor activity (in other words, "exercise") can be elicited and maintained in mice by manipulating the schedule of reinforcement. Our findings argue that the present technology might reduce the imposition of stress and motivational bias inherent in more traditional procedures for establishing exercise in laboratory rodents, while allowing for true random assignment to experimental groups. As interest in physical exercise as a modulating factor in numerous clinical conditions continues to grow, technologies like the one proposed here are likely to become critical in conducting future experiments along these lines.

  7. Divergent selection on home pen locomotor activity in a chicken model: Selection program, genetic parameters and direct response on activity and body weight

    PubMed Central

    2017-01-01

    General locomotor activity (GLA) in poultry has attracted attention, as it negatively influences production costs (energy expenditure and feed consumption) and welfare parameters (bone strength, litter quality, feather pecking and cannibalism). Laying hen lines diverging in the average level of spontaneous locomotor activity in the home pen were developed by genetic selection using the founder New Hampshire line. Activity was recorded using RFID technology at around five weeks of age during four to five days in the home pen. After initial phenotyping, the least active birds were selected for the low activity line and the most active for the high activity line, with no gene transfer between lines. In each of six generations, approximately ten sires were mated to twenty dams producing 158 to 334 offspring per line per generation. The response to selection was rapid and of a considerable magnitude. In sixth generation, the level of GLA was approximately halved in the low and doubled in the high line compared to the control (7.2, 14.9 and 28.7 recordings/h). Estimated heritability of locomotor activity in the low and high line was 0.38 and 0.33, respectively. Males, in general, were more active than females. High line birds were significantly heavier than low line birds. In fourth, fifth, and sixth generation, low as well as high line birds were lighter than control line birds. This selection experiment demonstrates variation in heritability for GLA and, as a result, genetically diverged lines have been developed. These lines can be used as models for further studies of underlying physiological, neural and molecular genetic mechanisms of spontaneous locomotor activity. PMID:28796792

  8. Habituation, Response to Novelty, and Dishabituation in Human Infants: Tests of a Dual-Process Theory of Visual Attention.

    ERIC Educational Resources Information Center

    Kaplan, Peter S.; Werner, John S.

    1986-01-01

    Tests infants' dual-process performance (a process mediating response decrements called habituation and a state-dependent process mediating response increments called sensitization) on visual habituation-dishabituation tasks. (HOD)

  9. Cocaine-induced locomotor activity in rats selectively bred for low and high voluntary running behavior.

    PubMed

    Brown, Jacob D; Green, Caroline L; Arthur, Ian M; Booth, Frank W; Miller, Dennis K

    2015-02-01

    The rewarding effects of physical activity and abused drugs are caused by stimulation of similar brain pathways. Low (LVR) and high (HVR) voluntary running lines were developed by selectively breeding Wistar rats on running distance performance on postnatal days 28-34. We hypothesized that LVR rats would be more sensitive to the locomotor-activating effects of cocaine than HVR rats due to their lower motivation for wheel running. We investigated how selection for LVR or HVR behavior affects inherited activity responses: (a) open field activity levels, (b) habituation to an open field environment, and (c) the locomotor response to cocaine. Open field activity was measured for 80 min on three successive days (days 1-3). Data from the first 20 min were analyzed to determine novelty-induced locomotor activity (day 1) and the habituation to the environment (days 1-3). On day 3, rats were acclimated to the chamber for 20 min and then received saline or cocaine (10, 20, or 30 mg/kg) injection. Dopamine transporter (DAT) protein in the nucleus accumbens was measured via Western blot. Selecting for low and high voluntary running behavior co-selects for differences in inherent (HVR > LVR) and cocaine-induced (LVR > HVR) locomotor activity levels. The differences in the selected behavioral measures do not appear to correlate with DAT protein levels. LVR and HVR rats are an intriguing physical activity model for studying the interactions between genes related to the motivation to run, to use drugs of abuse, and to exhibit locomotor activity.

  10. Resolution of a target-tracking optical novelty filter

    NASA Technical Reports Server (NTRS)

    Liu, Duncan T. H.; Cheng, Li-Jen

    1991-01-01

    The resolution of a target-tracking optical novelty filter is discussed in terms of the response time of the nonlinear medium, the speed of the target, and the resolution of the input device. Optical novelty filters using a faster nonlinear medium may have a higher output resolution. This is particularly true in the case of tracking high-speed targets. The potential of implementing high-resolution optical novelty filters using photorefractive GaAs is investigated experimentally.

  11. Locomotor response to exercise in relation to plasma lactate accumulation and heart rate in Andalusian and Anglo-Arabian horses.

    PubMed

    Muñoz, A; Santisteban, R; Rubio, M D; Riber, C; Agüera, E I; Castejón, F M

    1999-10-01

    To establish the effect of the locomotor pattern on heart rate (HR) and plasma lactate (LA), 28 horses, 18 Andalusian (AN) and 10 Anglo-Arabian (AA), aged 3-4 years, were studied. After a warm-up period, the horses performed a four-step test at 5, 6, 7 and 8 m/s, covering 1000 m at each velocity. HR was monitored, LA was analysed at rest and after each workload, and images were filmed. The locomotor parameters determined were stride duration (SD), frequency (SF) and length (SL), step and bipedal support durations, stance (restraint and propulsion) and swing phase durations, and stride vertical component. The HR and LA were significantly higher in the AN horses from velocities of 5 m/s. Similarly, the stride vertical component was higher in the AN horses at the trot and in the leading forelimbs at the gallop. Conversely, at all the galloping velocities, swing phase duration and stride length were longer in the AA horses. Significant correlations between HR, LA and locomotor pattern were only found in the AN horses. It was concluded that the greater stride vertical component in the AN horses limits SL and the cranial advancement of the hoof, with the result that reaching a longer SL triggers an increase in HR and LA. AA horses reach a balance between SL and SF, improving the efficiency of the gait.

  12. Neural responses in songbird forebrain reflect learning rates, acquired salience, and stimulus novelty after auditory discrimination training

    PubMed Central

    Phan, Mimi L.; Vicario, David S.

    2014-01-01

    How do social interactions form and modulate the neural representations of specific complex signals? This question can be addressed in the songbird auditory system. Like humans, songbirds learn to vocalize by imitating tutors heard during development. These learned vocalizations are important in reproductive and social interactions and in individual recognition. As a model for the social reinforcement of particular songs, male zebra finches were trained to peck for a food reward in response to one song stimulus (GO) and to withhold responding for another (NoGO). After performance reached criterion, single and multiunit neural responses to both trained and novel stimuli were obtained from multiple electrodes inserted bilaterally into two songbird auditory processing areas [caudomedial mesopallium (CMM) and caudomedial nidopallium (NCM)] of awake, restrained birds. Neurons in these areas undergo stimulus-specific adaptation to repeated song stimuli, and responses to familiar stimuli adapt more slowly than to novel stimuli. The results show that auditory responses differed in NCM and CMM for trained (GO and NoGO) stimuli vs. novel song stimuli. When subjects were grouped by the number of training days required to reach criterion, fast learners showed larger neural responses and faster stimulus-specific adaptation to all stimuli than slow learners in both areas. Furthermore, responses in NCM of fast learners were more strongly left-lateralized than in slow learners. Thus auditory responses in these sensory areas not only encode stimulus familiarity, but also reflect behavioral reinforcement in our paradigm, and can potentially be modulated by social interactions. PMID:25475353

  13. Neural responses in songbird forebrain reflect learning rates, acquired salience, and stimulus novelty after auditory discrimination training.

    PubMed

    Bell, Brittany A; Phan, Mimi L; Vicario, David S

    2015-03-01

    How do social interactions form and modulate the neural representations of specific complex signals? This question can be addressed in the songbird auditory system. Like humans, songbirds learn to vocalize by imitating tutors heard during development. These learned vocalizations are important in reproductive and social interactions and in individual recognition. As a model for the social reinforcement of particular songs, male zebra finches were trained to peck for a food reward in response to one song stimulus (GO) and to withhold responding for another (NoGO). After performance reached criterion, single and multiunit neural responses to both trained and novel stimuli were obtained from multiple electrodes inserted bilaterally into two songbird auditory processing areas [caudomedial mesopallium (CMM) and caudomedial nidopallium (NCM)] of awake, restrained birds. Neurons in these areas undergo stimulus-specific adaptation to repeated song stimuli, and responses to familiar stimuli adapt more slowly than to novel stimuli. The results show that auditory responses differed in NCM and CMM for trained (GO and NoGO) stimuli vs. novel song stimuli. When subjects were grouped by the number of training days required to reach criterion, fast learners showed larger neural responses and faster stimulus-specific adaptation to all stimuli than slow learners in both areas. Furthermore, responses in NCM of fast learners were more strongly left-lateralized than in slow learners. Thus auditory responses in these sensory areas not only encode stimulus familiarity, but also reflect behavioral reinforcement in our paradigm, and can potentially be modulated by social interactions.

  14. Biomimetic novelty detection

    NASA Astrophysics Data System (ADS)

    Ma, Lein W.; Szu, Harold

    2010-04-01

    In the crowded rain forest, how do animals locate camouflaged prey that resemble the environment, such as walking sticks? Birds will observe the suspected stick over a period of time to determine if its behavior matches that of a tree. If the stick's behavior exceeds normal tree behavior, such as moving faster than the other branches, the bird will determine that it is actually a walking stick and not a tree branch. Once this determination is made, they will prey on the insect. Studying this natural process of novelty detection, present in a variety of animals from birds to turkey vultures, can be beneficial for numerous human applications. The spatiotemporal novelty detector will be developed using self-referencing matched filters to go beyond auto-regression. This algorithm is more than the usual change detector for it will detect a novelty behavior that exceeds its predicted value based on past data, e.g. the bird who identifies a walking stick in the forest. A scalar model is presented; however, the application can be expanded to multiple modalities for more detailed applications. Some of these applications include gas pipeline leak detection, persistent surveillance, and the creation of a smart sensor web.

  15. Detection of novelty, but not memory of spatial habituation, is associated with an increase in phosphorylated cAMP response element-binding protein levels in the hippocampus.

    PubMed

    Winograd, Milena; Viola, Haydée

    2004-01-01

    There is a growing body of evidence showing that the formation of associative memories is associated with an increase in phosphorylated cAMP response element-binding protein (pCREB) levels. We recently reported increased pCREB levels in the rat hippocampus after an exploration to a novel environment. In the present work, we studied whether this increment in CREB activation is associated with the formation of memory of habituation to a novel environment or with the detection of novelty. Rats were submitted to consecutive open field sessions at 3-h intervals. Measurement of the hippocampal pCREB level, carried out 1 h after each training session, showed that (1) it did not increase when rats explored a familiar environment; (2) it did not increase after a reexposure that improves the memory of habituation; (3) it increased after a brief novel exploration unable to form memory of habituation; and (4) it increased in amnesic rats for spatial habituation. Taken as a whole, our results suggest that the elevated pCREB level after a single open field exploration is not associated with the memory formation of habituation. It is indeed associated with the detection of a novel environment.

  16. P2X7 receptors in body temperature, locomotor activity, and brain mRNA and lncRNA responses to sleep deprivation.

    PubMed

    Davis, Christopher J; Taishi, Ping; Honn, Kimberly A; Koberstein, John N; Krueger, James M

    2016-12-01

    The ionotropic purine type 2X7 receptor (P2X7R) is a nonspecific cation channel implicated in sleep regulation and brain cytokine release. Many endogenous rhythms covary with sleep, including locomotor activity and core body temperature. Furthermore, brain-hypothalamic cytokines and purines play a role in the regulation of these physiological parameters as well as sleep. We hypothesized that these parameters are also affected by the absence of the P2X7 receptor. Herein, we determine spontaneous expression of body temperature and locomotor activity in wild-type (WT) and P2X7R knockout (KO) mice and how they are affected by sleep deprivation (SD). We also compare hypothalamic, hippocampal, and cortical cytokine- and purine-related receptor and enzyme mRNA expressions before and after SD in WT and P2X7RKO mice. Next, in a hypothesis-generating survey of hypothalamic long noncoding (lnc) RNAs, we compare lncRNA expression levels between strains and after SD. During baseline conditions, P2X7RKO mice had attenuated temperature rhythms compared with WT mice, although locomotor activity patterns were similar in both strains. After 6 h of SD, body temperature and locomotion were enhanced to a greater extent in P2X7RKO mice than in WT mice during the initial 2-3 h after SD. Baseline mRNA levels of cortical TNF-α and P2X4R were higher in the KO mice than WT mice. In response to SD, the KO mice failed to increase hypothalamic adenosine deaminase and P2X4R mRNAs. Further, hypothalamic lncRNA expressions varied by strain, and with SD. Current data are consistent with a role for the P2X7R in thermoregulation and lncRNA involvement in purinergic signaling.

  17. Novelty-facilitated extinction: providing a novel outcome in place of an expected threat diminishes recovery of defensive responses.

    PubMed

    Dunsmoor, Joseph E; Campese, Vinn D; Ceceli, Ahmet O; LeDoux, Joseph E; Phelps, Elizabeth A

    2015-08-01

    Experimental extinction serves as a model for psychiatric treatments based on associative learning. However, the effects of extinction are often transient, as evidenced by postextinction return of defensive behaviors. From a therapeutic perspective, an inherent problem with extinction may be that mere omission of threat is not sufficient to reduce future threat uncertainty. The current study tested an augmented form of extinction that replaced, rather than merely omitted, expected threat outcomes with novel nonthreat outcomes, with the goal of reducing postextinction return of defensive behaviors. Thirty-two healthy male Sprague-Dawley rats and 47 human adults underwent threat conditioning to a conditioned stimulus paired with an electrical shock. Subjects then underwent a standard extinction protocol with shock omitted or an augmented extinction protocol wherein the shock was replaced by a surprising tone. Tests of postextinction recovery occurred 24 hours later in the absence of the tone. Replacing the shock with a novel nonthreat outcome, as compared with shock omission, reduced postextinction recovery (freezing in rats and anticipatory skin conductance responses in humans) when tested 24 hours later. Self-reported intolerance of uncertainty was positively correlated with recovery following standard extinction in humans, providing new evidence that postextinction recovery is related to sensitivity to future threat uncertainty. These findings provide cross-species evidence of a novel strategy to enhance extinction that may have broad implications for how to override associative learning that has become maladaptive and offer a simple technique that could be straightforwardly adapted and implemented in clinical situations. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  18. Effect of environmental temperature on sleep, locomotor activity, core body temperature and immune responses of C57BL/6J mice.

    PubMed

    Jhaveri, K A; Trammell, R A; Toth, L A

    2007-10-01

    Ambient temperature exerts a prominent influence on sleep. In rats and humans, low ambient temperatures generally impair sleep, whereas higher temperatures tend to promote sleep. The purpose of the current study was to evaluate sleep patterns and core body temperatures of C57BL/6J mice at ambient temperatures of 22, 26 and 30 degrees C under baseline conditions, after sleep deprivation (SD), and after infection with influenza virus. C57BL/6J mice were surgically implanted with electrodes for recording electroencephalogram (EEG) and electromyogram (EMG) and with intraperitoneal transmitters for recording core body temperature (T(c)) and locomotor activity. The data indicate that higher ambient temperatures (26 and 30 degrees C) promote spontaneous slow wave sleep (SWS) in association with reduced delta wave amplitude during SWS in C57BL/6J mice. Furthermore, higher ambient temperatures also promote recuperative sleep after SD. Thus, in mice, higher ambient temperatures reduced sleep depth under normal conditions, but augmented the recuperative response to sleep loss. Mice infected with influenza virus while maintained at 22 or 26 degrees C developed more SWS, less rapid eye movement sleep, lower locomotor activity and greater hypothermia than did mice maintained at 30 degrees C during infection. In addition, despite equivalent viral titers, mice infected with influenza virus at 30 degrees C showed less leucopenia and lower cytokine induction as compared with 22 and 26 degrees C, respectively, suggesting that less inflammation develops at the higher ambient temperature.

  19. Differential effects of serotonin (5-HT)2 receptor-targeting ligands on locomotor responses to nicotine-repeated treatment.

    PubMed

    Zaniewska, Magdalena; McCreary, Andrew C; Wydra, Karolina; Filip, Małgorzata

    2010-07-01

    We verified the hypothesis that serotonin (5-HT)(2) receptors control the locomotor effects of nicotine (0.4 mg kg(-1)) in rats by using the 5-HT(2A) receptor antagonist M100907, the preferential 5-HT(2A) receptor agonist DOI, the 5-HT(2C) receptor antagonist SB 242084, and the 5-HT(2C) receptor agonists Ro 60-0175 and WAY 163909. Repeated pairings of a test environment with nicotine for 5 days, on Day 10 significantly augmented the locomotor activity following nicotine administration. Of the investigated 5-HT(2) receptor ligands, M100907 (2 mg kg(-1)) or DOI (1 mg kg(-1)) administered during the first 5 days in combination with nicotine attenuated or enhanced, respectively, the development of nicotine sensitization. Given acutely on Day 10, M100907 (2 mg kg(-1)), Ro 60-0175 (1 mg kg(-1)), and WAY 163909 (1.5 mg kg(-1)) decreased the expression of nicotine sensitization. In another set of experiments, where the nicotine challenge test was performed on Day 15 in animals treated repeatedly (Days: 1-5, 10) with nicotine, none of 5-HT(2) receptor ligands administered during the second withdrawal period (Days: 11-14) to nicotine-treated rats altered the sensitizing effect of nicotine given on Day 15. Our data indicate that 5-HT(2A) receptors (but not 5-HT(2C) receptors) play a permissive role in the sensitizing effects of nicotine, while stimulation of 5-HT(2A) receptors enhances the development of nicotine sensitization and activation of 5-HT(2C) receptors is essential for the expression of nicotine sensitization. Repeated treatment with the 5-HT(2) receptor ligands within the second nicotine withdrawal does not inhibit previously established sensitization.

  20. Neonatal quinpirole treatment enhances locomotor activation and dopamine release in the nucleus accumbens core in response to amphetamine treatment in adulthood

    PubMed Central

    Cope, Zackary A.; Huggins, Kimberly N.; Sheppard, A. Brianna; Noel, Daniel M.; Roane, David S.; Brown, Russell W.

    2009-01-01

    Neonatal quinpirole treatment to rats produces long-term increases in D2 receptor sensitivity that persists throughout the animal's lifetime, a phenomenon referred to as D2 priming. Male and female Sprague-dawley rats were administered quinpirole (1mg/kg) or saline from postnatal days (P)1–11. At P60, all animals were given an injection of quinpirole (100 ug/kg), and results showed that rats neonatally treated with quinpirole demonstrated enhanced yawning in response to quinprole, verifying D2 receptor priming because yawning is a D2 receptor mediated event. Beginning 1–3 days later, locomotor sensitization was tested through administration of d-amphetamine (1mg/kg) or saline every other day over 14 days, and horizontal activity and turning behavior were analyzed. Findings indicated that D2-priming enhanced horizontal activity in response to amphetamine in females compared to males at days 1 and 4 of locomotor sensitization testing, and D2-priming enhanced turning in response to amphetamine. Seven to 10 days after sensitization was complete, microdialysis of the NAcc core was performed using a cumulative dosing regimen of amphetamine (0.1 – 3.0 mg/kg). D2-primed rats administered amphetamine demonstrated a 500% increase in accumbal DA overflow compared to control rats administered amphetamine. Additionally, amphetamine produced a significant increase in NE overflow compared to controls, but this was unaffected by D2 priming. These results indicate that D2 receptor priming as is produced by neonatal quinpirole treatment robustly enhances behavioral activation and accumbal DA overflow in response to amphetamine, which may underlie increases in psychostimulant use and abuse within the psychotic population where increased D2 receptor sensitivity is a hallmark. PMID:19953655

  1. Combined Scopolamine and Ethanol Treatment Results in a Locomotor Stimulant Response Suggestive of Synergism That is Not Blocked by Dopamine Receptor Antagonists

    PubMed Central

    Scibelli, Angela C.; Phillips, Tamara J.

    2010-01-01

    Background Muscarinic acetylcholine receptors (mAChRs) are well positioned to mediate ethanol’s stimulant effects. To investigate this possibility, we examined the effects of scopolamine, a receptor subtype nonselective mAChR antagonist, on ethanol-induced stimulation in genotypes highly sensitive to this effect of ethanol. We also investigated whether the dopamine D1-like receptor antagonist, SCH-23390 or the dopamine D2-like receptor antagonist, haloperidol, could block the extreme stimulant response found following co-administration of scopolamine and ethanol. Methods Scopolamine (0, 0.0625, 0.125, 0.25, or 0.5 mg/kg) was given 10 minutes prior to saline or ethanol (0.75 to 2 g/kg) to female FAST (Experiment I) or DBA/2J (Experiment II) mice that were then tested for locomotion for 30 minutes. In Experiments III and IV, respectively, SCH-23390 (0, 0.015, or 0.03 mg/kg) was given 10 minutes prior, and haloperidol (0, 0.08, or 0.16 mg/kg) was given 2 minutes prior, to scopolamine (0 or 0.5 mg/kg), followed 10 minutes later by saline or ethanol (1.5 g/kg) and female DBA/2J mice were tested for locomotion for 30 minutes. Results FAST and DBA/2J mice displayed a robust enhancement of the locomotor effects of ethanol following pretreatment with scopolamine that was suggestive of synergism. SCH-23390 had no effect on the response to the scopolamine + ethanol drug combination, nor did it attenuate ethanol- or scopolamine-induced locomotor activity. Haloperidol, while attenuating the effects of ethanol, was not able to block the effects of scopolamine or the robust response to the scopolamine-ethanol drug combination. Conclusions These results suggest that while muscarinic receptor antagonism robustly enhances acute locomotor stimulation to ethanol, dopamine receptors are not involved in the super-additive interaction of scopolamine and ethanol treatment. They also suggest that in addition to cautions regarding the use of alcohol when scopolamine is clinically

  2. Novelty-Driven Cooperative Coevolution.

    PubMed

    Gomes, Jorge; Mariano, Pedro; Christensen, Anders Lyhne

    2015-12-14

    Cooperative coevolutionary algorithms (CCEAs) rely on multiple coevolving populations for the evolution of solutions composed of coadapted components. CCEAs enable, for instance, the evolution of cooperative multiagent systems composed of heterogeneous agents, where each agent is modelled as a component of the solution. Previous works have, however, shown that CCEAs are biased toward stability: the evolutionary process tends to converge prematurely to stable states instead of (near-)optimal solutions. In this study, we show how novelty search can be used to avoid the counterproductive attraction to stable states in coevolution. Novelty search is an evolutionary technique that drives evolution toward behavioural novelty and diversity rather than exclusively pursuing a static objective. We evaluate three novelty-based approaches that rely on, respectively (1) the novelty of the team as a whole, (2) the novelty of the agents' individual behaviour, and (3) the combination of the two. We compare the proposed approaches with traditional fitness-driven cooperative coevolution in three simulated multirobot tasks. Our results show that team-level novelty scoring is the most effective approach, significantly outperforming fitness-driven coevolution at multiple levels. Novelty-driven cooperative coevolution can substantially increase the potential of CCEAs while maintaining a computational complexity that scales well with the number of populations.

  3. The dynamics of correlated novelties

    NASA Astrophysics Data System (ADS)

    Tria, F.; Loreto, V.; Servedio, V. D. P.; Strogatz, S. H.

    2014-07-01

    Novelties are a familiar part of daily life. They are also fundamental to the evolution of biological systems, human society, and technology. By opening new possibilities, one novelty can pave the way for others in a process that Kauffman has called ``expanding the adjacent possible''. The dynamics of correlated novelties, however, have yet to be quantified empirically or modeled mathematically. Here we propose a simple mathematical model that mimics the process of exploring a physical, biological, or conceptual space that enlarges whenever a novelty occurs. The model, a generalization of Polya's urn, predicts statistical laws for the rate at which novelties happen (Heaps' law) and for the probability distribution on the space explored (Zipf's law), as well as signatures of the process by which one novelty sets the stage for another. We test these predictions on four data sets of human activity: the edit events of Wikipedia pages, the emergence of tags in annotation systems, the sequence of words in texts, and listening to new songs in online music catalogues. By quantifying the dynamics of correlated novelties, our results provide a starting point for a deeper understanding of the adjacent possible and its role in biological, cultural, and technological evolution.

  4. Emergent exploration via novelty management.

    PubMed

    Gordon, Goren; Fonio, Ehud; Ahissar, Ehud

    2014-09-17

    When encountering novel environments, animals perform complex yet structured exploratory behaviors. Despite their typical structuring, the principles underlying exploratory patterns are still not sufficiently understood. Here we analyzed exploratory behavioral data from two modalities: whisking and locomotion in rats and mice. We found that these rodents maximized novelty signal-to-noise ratio during each exploration episode, where novelty is defined as the accumulated information gain. We further found that these rodents maximized novelty during outbound exploration, used novelty-triggered withdrawal-like retreat behavior, and explored the environment in a novelty-descending sequence. We applied a hierarchical curiosity model, which incorporates these principles, to both modalities. We show that the model captures the major components of exploratory behavior in multiple timescales: single excursions, exploratory episodes, and developmental timeline. The model predicted that novelty is managed across exploratory modalities. Using a novel experimental setup in which mice encountered a novel object for the first time in their life, we tested and validated this prediction. Further predictions, related to the development of brain circuitry, are described. This study demonstrates that rodents select exploratory actions according to a novelty management framework and suggests a plausible mechanism by which mammalian exploration primitives can be learned during development and integrated in adult exploration of complex environments. Copyright © 2014 the authors 0270-6474/14/3412646-16$15.00/0.

  5. The dynamics of correlated novelties

    PubMed Central

    Tria, F.; Loreto, V.; Servedio, V. D. P.; Strogatz, S. H.

    2014-01-01

    Novelties are a familiar part of daily life. They are also fundamental to the evolution of biological systems, human society, and technology. By opening new possibilities, one novelty can pave the way for others in a process that Kauffman has called “expanding the adjacent possible”. The dynamics of correlated novelties, however, have yet to be quantified empirically or modeled mathematically. Here we propose a simple mathematical model that mimics the process of exploring a physical, biological, or conceptual space that enlarges whenever a novelty occurs. The model, a generalization of Polya's urn, predicts statistical laws for the rate at which novelties happen (Heaps' law) and for the probability distribution on the space explored (Zipf's law), as well as signatures of the process by which one novelty sets the stage for another. We test these predictions on four data sets of human activity: the edit events of Wikipedia pages, the emergence of tags in annotation systems, the sequence of words in texts, and listening to new songs in online music catalogues. By quantifying the dynamics of correlated novelties, our results provide a starting point for a deeper understanding of the adjacent possible and its role in biological, cultural, and technological evolution. PMID:25080941

  6. Involvement of the TRPV1 channel in the modulation of spontaneous locomotor activity, physical performance and physical exercise-induced physiological responses

    PubMed Central

    Hudson, A.S.R.; Kunstetter, A.C.; Damasceno, W.C.; Wanner, S.P.

    2016-01-01

    Physical exercise triggers coordinated physiological responses to meet the augmented metabolic demand of contracting muscles. To provide adequate responses, the brain must receive sensory information about the physiological status of peripheral tissues and organs, such as changes in osmolality, temperature and pH. Most of the receptors involved in these afferent pathways express ion channels, including transient receptor potential (TRP) channels, which are usually activated by more than one type of stimulus and are therefore considered polymodal receptors. Among these TRP channels, the TRPV1 channel (transient receptor potential vanilloid type 1 or capsaicin receptor) has well-documented functions in the modulation of pain sensation and thermoregulatory responses. However, the TRPV1 channel is also expressed in non-neural tissues, suggesting that this channel may perform a broad range of functions. In this review, we first present a brief overview of the available tools for studying the physiological roles of the TRPV1 channel. Then, we present the relationship between the TRPV1 channel and spontaneous locomotor activity, physical performance, and modulation of several physiological responses, including water and electrolyte balance, muscle hypertrophy, and metabolic, cardiovascular, gastrointestinal, and inflammatory responses. Altogether, the data presented herein indicate that the TPRV1 channel modulates many physiological functions other than nociception and thermoregulation. In addition, these data open new possibilities for investigating the role of this channel in the acute effects induced by a single bout of physical exercise and in the chronic effects induced by physical training. PMID:27191606

  7. Involvement of the TRPV1 channel in the modulation of spontaneous locomotor activity, physical performance and physical exercise-induced physiological responses.

    PubMed

    Hudson, A S R; Kunstetter, A C; Damasceno, W C; Wanner, S P

    2016-01-01

    Physical exercise triggers coordinated physiological responses to meet the augmented metabolic demand of contracting muscles. To provide adequate responses, the brain must receive sensory information about the physiological status of peripheral tissues and organs, such as changes in osmolality, temperature and pH. Most of the receptors involved in these afferent pathways express ion channels, including transient receptor potential (TRP) channels, which are usually activated by more than one type of stimulus and are therefore considered polymodal receptors. Among these TRP channels, the TRPV1 channel (transient receptor potential vanilloid type 1 or capsaicin receptor) has well-documented functions in the modulation of pain sensation and thermoregulatory responses. However, the TRPV1 channel is also expressed in non-neural tissues, suggesting that this channel may perform a broad range of functions. In this review, we first present a brief overview of the available tools for studying the physiological roles of the TRPV1 channel. Then, we present the relationship between the TRPV1 channel and spontaneous locomotor activity, physical performance, and modulation of several physiological responses, including water and electrolyte balance, muscle hypertrophy, and metabolic, cardiovascular, gastrointestinal, and inflammatory responses. Altogether, the data presented herein indicate that the TPRV1 channel modulates many physiological functions other than nociception and thermoregulation. In addition, these data open new possibilities for investigating the role of this channel in the acute effects induced by a single bout of physical exercise and in the chronic effects induced by physical training.

  8. Effect of environmental temperature on sleep, locomotor activity, core body temperature and immune responses of C57BL/6J mice

    PubMed Central

    Jhaveri, KA; Trammell, RA; Toth, LA

    2007-01-01

    Ambient temperature exerts a prominent influence on sleep. In rats and humans, low ambient temperatures generally impair sleep, whereas higher temperatures tend to promote sleep. The purpose of the current study was to evaluate sleep patterns and core body temperatures of C57BL/6J mice at ambient temperatures of 22°C, 26°C and 30°C under baseline conditions, after sleep deprivation (SD), and after infection with influenza virus. C57BL/6J mice were surgically implanted with electrodes for recording electroencephalogram (EEG) and electromyogram (EMG) and with intraperitoneal transmitters for recording core body temperature (Tc) and locomotor activity. The data indicate that higher ambient temperatures (26°C and 30°C) promote spontaneous slow wave sleep (SWS) in association with reduced delta wave amplitude during SWS in C57BL/6J mice. Furthermore, higher ambient temperatures also promote recuperative sleep after SD. Thus, in mice, higher ambient temperatures reduced sleep depth under normal conditions, but augmented the recuperative response to sleep loss. Mice infected with influenza virus while maintained at 22 or 26°C developed more SWS, less rapid eye movement sleep, lower locomotor activity and greater hypothermia than did mice maintained at 30°C during infection. In addition, despite equivalent viral titers, mice infected with influenza virus at 30°C showed less leucopenia and lower cytokine induction as compared with 22 and 26°C, respectively, suggesting that less inflammation develops at the higher ambient temperature. PMID:17467232

  9. Locomotor Inhibition in Adult Horses Faced to Stressors: A Single Postpartum Experience May be Enough!

    PubMed Central

    Durier, Virginie; Henry, Séverine; Sankey, Carol; Sizun, Jacques; Hausberger, Martine

    2012-01-01

    Despite the number of postpartum handling that a newborn experiences, few studies focus on their long-term consequences. In rats, regular long separations from the mother, during the early life, led to modifications of the locomotor activity when the animal is confronted to a stressor. In horses, one component of the behavioral response to stressful situation is active locomotion. We wondered if the routine postpartum handling undergone by foals, would affect their level of reactivity or the way they express their stress, when older. One single prolonged bout of handling just after birth clearly affected later adult expression of stress reactivity. In social separation associated with novelty, handled, and unhandled horses produced an equal amount of whinnies, showing a similar vocal response to stress. However, both groups differed in their locomotor response to the situations. Early handled foals expressed less of the active forms of locomotion than the control group. Our findings highlight the need of further reflections on long-term effects of routine handlings procedures close to birth. PMID:23112783

  10. THE CCK-SYSTEM UNDERPINS NOVELTY-SEEKING BEHAVIOR IN THE RAT: GENE EXPRESSION AND PHARMACOLOGICAL ANALYSES

    PubMed Central

    Ballaz, Santiago J.; Akil, Huda; Watson, Stanley J.

    2008-01-01

    Cholecystokinin (CCK) and its receptor CCK-2R have been shown to promote emotional responsivity and behavioral sensitization to psychostimulants in the rat. An animal model has been developed based on locomotor response to a novel inescapable environment. Animals exhibiting consistent differences in locomotor response to novelty have been termed as High and Low Responder rats (HR and LR respectively). This paradigm is deemed to model sensation-seeking, a personality trait closely associated with substance abuse. The present study provides genetic and pharmacological evidence that the CCK-ergic system modulates this behavior. Distinctive patterns of CCK-related gene expression in HR and LR animals occurred beyond the mesolimbic pathways. CCK gene expression was higher in hippocampus, amygdala, and prefrontal cortex, but lower in the ventral tegmental area of HR relative to LR rats. Levels of CCK-2R mRNA were more elevated in LR animals in some areas of the forebrain such as the prefrontal cortex, nucleus accumbens, and hippocampus. Additionally, CCK-2R blockade with the antagonist LY225.910 (0.5 mg/Kg) removed phenotype differences in sustained exploration of novel stimuli (i.e., a novel-object) in HR and LR rats exposed to an enriched open-field test series. Finally, CCK-2R blockade also altered M2 and 5-HT7 receptor gene expression in the mediodorsal thalamus (a strategic structure for corticothalamic trafficking) in a phenotype-dependent manner. Taken together, the findings reported here suggest that distinct CCK-ergic function may contribute to promoting individual differences in novelty-seeking behavior. PMID:18410964

  11. Locomotor exercise in weightlessness

    NASA Technical Reports Server (NTRS)

    Thornton, W.; Whitmore, H.

    1991-01-01

    The requirements for exercise in space by means of locomotion are established and addressed with prototype treadmills for use during long-duration spaceflight. The adaptation of the human body to microgravity is described in terms of 1-G locomotor biomechanics, the effects of reduced activity, and effective activity-replacement techniques. The treadmill is introduced as a complement to other techniques of force replacement with reference given to the angle required for exercise. A motor-driven unit is proposed that can operate at a variety of controlled speeds and equivalent grades. The treadmills permit locomotor exercise as required for long-duration space travel to sustain locomotor and cardiorespiratory capacity at a level consistent with postflight needs.

  12. Novelty, stimulus control, and operant variability

    PubMed Central

    Shahan, Timothy A.; Chase, Philip N.

    2002-01-01

    Although behavior analysis has been criticized for failure to account for response novelty, many common behavior-analytic concepts and processes (e.g., selectionism, the operant, reinforcement, and stimulus control) assume variability both in the environment and in behavior. The importance of the relation between variability and novelty, particularly for verbal behavior, is discussed, and concepts used to account for novel behavior are examined. Experimental findings also are reviewed that suggest that variability in behavior can come under discriminative control, and these findings are applied to describe novel instances of behavior that may arise during problem solving. We conclude that variations provided and selected by the terms of the three-term contingency are powerful means for understanding novel behavior. PMID:22478385

  13. NOVELTY DETECTION UNDER CHANGING ENVIRONMENTAL CONDITIONS

    SciTech Connect

    H. SOHN; K. WORDER; C. R. FARRAR

    2001-04-01

    The primary objective of novelty detection is to examine a system's dynamic response to determine if the system significantly deviates from an initial baseline condition. In reality, the system is often subject to changing environmental and operation conditions that affect its dynamic characteristics. Such variations include changes in loading, boundary conditions, temperature, and moisture. Most damage diagnosis techniques, however, generally neglect the effects of these changing ambient conditions. Here, a novelty detection technique is developed explicitly taking into account these natural variations of the system in order to minimize false positive indications of true system changes. Auto-associative neural networks are employed to discriminate system changes of interest such as structural deterioration and damage from the natural variations of the system.

  14. Novelty detection under changing environmental conditions

    NASA Astrophysics Data System (ADS)

    Sohn, Hoon; Worden, Keith; Farrar, Charles R.

    2001-07-01

    The primary objective of novelty detection is to examine a system's dynamic response to determine if the system significantly deviates from an initial baseline condition. In reality, the system is often subject to changing environmental and operation conditions that affect its dynamic characteristics. Such variations include changes in loading, boundary conditions, temperature, and moisture. Most damage diagnosis techniques, however, generally neglect the effects of these changing ambient conditions. Here, a novelty detection technique is developed explicitly taking into account these natural variations of the system in order to minimize false positive indications of true system changes. Auto-associative neural networks are employed to discriminate system changes of interest such as structural deterioration and damage from the natural variations of the system.

  15. Contribution of impulsivity and novelty-seeking to the acquisition and maintenance of MDMA self-administration.

    PubMed

    Bird, Judith; Schenk, Susan

    2013-07-01

    It has been suggested that the response to novelty and impulsivity predict the latency to acquisition and maintenance of drug self-administration, respectively. The aim of this study was to examine the relationship between these two traits and (1) the latency to acquisition and (2) maintenance (drug-seeking) of 3,4-methylenedioxymethamphetamine (MDMA) self -administration. Impulsivity, measured as premature responding on the five-choice serial reaction time task (5-CSRTT), and novelty-seeking, measured as the locomotor response in a novel environment, were measured prior to self-administration. Latency to acquisition was determined as the number of test sessions required to self-administer an initial criterion of 90 infusions of 1.0 mg/kg/infusion, as well as an additional 150 infusions of 0.5 mg/kg/infusion MDMA. For some rats, the ability of MDMA [0, 5.0 or 10.0 mg/kg, intraperitoneal (IP)] to produce drug-seeking was subsequently measured, and for others, impulsivity was again measured following self-administration. Novelty-seeking was not significantly correlated with either the acquisition or drug-seeking measures of MDMA self-administration. Impulsivity was not significantly correlated with the latency to acquire self-administration of MDMA, but was significantly and positively correlated with the magnitude of MDMA-produced drug-seeking. Furthermore, MDMA self-administration produced a number of notable, but transient, deficits in the 5-CSRTT; there was an increase in omission rate and a delayed increase in premature responses in particular. These findings suggest that impulsivity, but not sensation seeking, might be a risk factor for the development of compulsive drug-seeking following withdrawal from MDMA self-administration.

  16. Revisiting the Novelty Effect: When Familiarity, Not Novelty, Enhances Memory

    ERIC Educational Resources Information Center

    Poppenk, J.; Kohler, S.; Moscovitch, M.

    2010-01-01

    Reports of superior memory for novel relative to familiar material have figured prominently in recent theories of memory. However, such "novelty effects" are incongruous with long-standing observations that familiar items are remembered better. In 2 experiments, we explored whether this discrepancy was explained by differences in the…

  17. Revisiting the Novelty Effect: When Familiarity, Not Novelty, Enhances Memory

    ERIC Educational Resources Information Center

    Poppenk, J.; Kohler, S.; Moscovitch, M.

    2010-01-01

    Reports of superior memory for novel relative to familiar material have figured prominently in recent theories of memory. However, such "novelty effects" are incongruous with long-standing observations that familiar items are remembered better. In 2 experiments, we explored whether this discrepancy was explained by differences in the…

  18. Neonatal +-methamphetamine exposure in rats alters adult locomotor responses to dopamine D1 and D2 agonists and to a glutamate NMDA receptor antagonist, but not to serotonin agonists.

    PubMed

    Graham, Devon L; Amos-Kroohs, Robyn M; Braun, Amanda A; Grace, Curtis E; Schaefer, Tori L; Skelton, Matthew R; Williams, Michael T; Vorhees, Charles V

    2013-03-01

    Neonatal exposure to (+)-methamphetamine (Meth) results in long-term behavioural abnormalities but its developmental mechanisms are unknown. In a series of experiments, rats were treated from post-natal days (PD) 11-20 (stage that approximates human development from the second to third trimester) with Meth or saline and assessed using locomotor activity as the readout following pharmacological challenge doses with dopamine, serotonin and glutamate agonists or antagonists during adulthood. Exposure to Meth early in life resulted in an exaggerated adult locomotor hyperactivity response to the dopamine D1 agonist SKF-82958 at multiple doses, a high dose only under-response activating effect of the D2 agonist quinpirole, and an exaggerated under-response to the activating effect of the N-methyl-d-aspartic acid (NMDA) receptor antagonist, MK-801. No change in locomotor response was seen following challenge with the 5-HT releaser p-chloroamphetamine or the 5-HT2/3 receptor agonist, quipazine. These are the first data to show that PD 11-20 Meth exposure induces long-lasting alterations to dopamine D1, D2 and glutamate NMDA receptor function and may suggest how developmental Meth exposure leads to many of its long-term adverse effects.

  19. An Evolutionarily Conserved Switch in Response to GABA Affects Development and Behavior of the Locomotor Circuit of Caenorhabditis elegans

    PubMed Central

    Han, Bingjie; Bellemer, Andrew; Koelle, Michael R.

    2015-01-01

    The neurotransmitter gamma-aminobutyric acid (GABA) is depolarizing in the developing vertebrate brain, but in older animals switches to hyperpolarizing and becomes the major inhibitory neurotransmitter in adults. We discovered a similar developmental switch in GABA response in Caenorhabditis elegans and have genetically analyzed its mechanism and function in a well-defined circuit. Worm GABA neurons innervate body wall muscles to control locomotion. Activation of GABAA receptors with their agonist muscimol in newly hatched first larval (L1) stage animals excites muscle contraction and thus is depolarizing. At the mid-L1 stage, as the GABAergic neurons rewire onto their mature muscle targets, muscimol shifts to relaxing muscles and thus has switched to hyperpolarizing. This muscimol response switch depends on chloride transporters in the muscles analogous to those that control GABA response in mammalian neurons: the chloride accumulator sodium-potassium-chloride-cotransporter-1 (NKCC-1) is required for the early depolarizing muscimol response, while the two chloride extruders potassium-chloride-cotransporter-2 (KCC-2) and anion-bicarbonate-transporter-1 (ABTS-1) are required for the later hyperpolarizing response. Using mutations that disrupt GABA signaling, we found that neural circuit development still proceeds to completion but with an ∼6-hr delay. Using optogenetic activation of GABAergic neurons, we found that endogenous GABAA signaling in early L1 animals, although presumably depolarizing, does not cause an excitatory response. Thus a developmental depolarizing-to-hyperpolarizing shift is an ancient conserved feature of GABA signaling, but existing theories for why this shift occurs appear inadequate to explain its function upon rigorous genetic analysis of a well-defined neural circuit. PMID:25644702

  20. Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates.

    PubMed

    Drouin, Candice; Darracq, Laurent; Trovero, Fabrice; Blanc, Gérard; Glowinski, Jacques; Cotecchia, Susanna; Tassin, Jean-Pol

    2002-04-01

    Drugs of abuse, such as psychostimulants and opiates, are generally considered as exerting their locomotor and rewarding effects through an increased dopaminergic transmission in the nucleus accumbens. Noradrenergic transmission may also be implicated because most psychostimulants increase norepinephrine (NE) release, and numerous studies have indicated interactions between noradrenergic and dopaminergic neurons through alpha1-adrenergic receptors. However, analysis of the effects of psychostimulants after either destruction of noradrenergic neurons or pharmacological blockade of alpha1-adrenergic receptors led to conflicting results. Here we show that the locomotor hyperactivities induced by d-amphetamine (1-3 mg/kg), cocaine (5-20 mg/kg), or morphine (5-10 mg/kg) in mice lacking the alpha1b subtype of adrenergic receptors were dramatically decreased when compared with wild-type littermates. Moreover, behavioral sensitizations induced by d-amphetamine (1-2 mg/kg), cocaine (5-15 mg/kg), or morphine (7.5 mg/kg) were also decreased in knock-out mice when compared with wild-type. Ruling out a neurological deficit in knock-out mice, both strains reacted similarly to novelty, to intraperitoneal saline, or to the administration of scopolamine (1 mg/kg), an anti-muscarinic agent. Finally, rewarding properties could not be observed in knock-out mice in an oral preference test (cocaine and morphine) and conditioned place preference (morphine) paradigm. Because catecholamine tissue levels, autoradiography of D1 and D2 dopaminergic receptors, and of dopamine reuptake sites and locomotor response to a D1 agonist showed that basal dopaminergic transmission was similar in knock-out and wild-type mice, our data indicate a critical role of alpha1b-adrenergic receptors and noradrenergic transmission in the vulnerability to addiction.

  1. Optical Correlator Performs Novelty Filtering

    NASA Technical Reports Server (NTRS)

    Liu, Duncan Tsuen-Hsi; Chao, Tien-Hsin; Cheng, Li-Jen

    1994-01-01

    Experimental real-time optical correlator performs correlation and novelty filtering in photorefractive crystal. Crystal oriented enabling cross-polarization diffraction: together with polarizing beam splitter, increases signal-to-noise ratio. Laser and optical components expand, collimate, and divide laser beam.

  2. A comparison of locomotor responses to some psychotropic drugs and cerebral receptors in the Acomys cahirinus and the laboratory mouse.

    PubMed

    Marona-Lewicka, D; Michaluk, J; Antkiewicz-Michaluk, L; Vetulani, J

    1987-01-01

    Comparative studies of the laboratory mouse and Acomys cahirinus have shown differences in their motor activity patterns and motor responses to morphine, apomorphine and clonidine. The two species also differed in respect of the density of cerebral alpha 2-adrenergic receptors, but no significant differences between other types of receptors (alpha 1-adrenergic, beta-adrenergic, opiate mu and delta, and spiroperidol binding sites) were found. It is suggested that the high excitability of the Acomys may be related to a deficit in the inhibitory noradrenergic transmission in the central nervous system.

  3. Auditory stimuli enhance MDMA-conditioned reward and MDMA-induced nucleus accumbens dopamine, serotonin and locomotor responses.

    PubMed

    Feduccia, Allison A; Duvauchelle, Christine L

    2008-10-22

    MDMA (3,4-methylenedioxymethamphetamine), also known as ecstasy, is a popular drug often taken in environments rich in audio and visual stimulation, such as clubs and dance parties. The present experiments were conducted to test the notion that auditory stimulation influences the rewarding effects of MDMA. In Experiment 1, a conditioned place preference (CPP) procedure was conducted in which rats received MDMA (1.5mg/kg, s.c.) in a distinctive environment accompanied by music (65-75dB), white noise (70dB), or no added sound. Animals were pretreated with saline on alternating days in an alternate environment. Results revealed CPP in animals exposed to white noise during MDMA trials. For Experiment 2, rats from Experiment 1 had access to operant levers that delivered intravenous MDMA (0.5mg/kg/inj) or saline (0.1ml) on alternate days in the presence or absence of the same types of auditory stimuli as previously experienced. After three each of MDMA and non-reinforced (saline) sessions, animals were tested for NAcc DA and 5-HT responses to MDMA (1.5mg/kg) or saline under the same stimulus conditions. Findings revealed that NAcc DA and 5-HT increased after an MDMA injection, and both DA and 5-HT were significantly highest in animals exposed to music during the test session. These results indicate that paired sensorial stimuli can engage the same systems activated during drug use and enhance neurochemical and behavioral responses to MDMA administration.

  4. Unraveling Effects of Novelty on Creativity

    ERIC Educational Resources Information Center

    Gillebaart, Marleen; Förster, Jens; Rotteveel, Mark; Jehle, Astrid C. M.

    2013-01-01

    Novelty is inherent to creative processes. A positive effect of novelty on creative task performance was therefore predicted. However, creativity can benefit from divergent, as well as convergent thinking. Subsequently, novelty may benefit creative performance when divergent thinking is required, but it could inhibit creative performance when…

  5. Unraveling Effects of Novelty on Creativity

    ERIC Educational Resources Information Center

    Gillebaart, Marleen; Förster, Jens; Rotteveel, Mark; Jehle, Astrid C. M.

    2013-01-01

    Novelty is inherent to creative processes. A positive effect of novelty on creative task performance was therefore predicted. However, creativity can benefit from divergent, as well as convergent thinking. Subsequently, novelty may benefit creative performance when divergent thinking is required, but it could inhibit creative performance when…

  6. Higher locomotor response to cocaine in female (vs. male) rats selectively bred for high (HiS) and low (LoS) saccharin intake

    PubMed Central

    Carroll, Marilyn E.; Anderson, Marissa M.; Morgan, Andrew D.

    2013-01-01

    Rats selectively bred for high saccharin consumption (HiS) self-administer more oral ethanol and i.v. cocaine than those selectively bred for low saccharin consumption (LoS). Male and female drug-seeking-prone (HiS) and –resistant (LoS) rats were used in the present experiment to test the prediction that cocaine-induced locomotor activity and sensitization varied with sex and their selective breeding status (HiS and LoS). All rats were intermittently exposed over 2 weeks to pairs of sequential saline and cocaine injections, separated by 45 min. The first 5 pairs of injections, each separated by 2-3 days (10-12 days total), were given to examine the development of cocaine-induced locomotor activity and the development of locomotor sensitization, which was determined by comparing the effects of cocaine injection 1 with injection 6, which was given 2 weeks after the 5 pairs of intermittent injections. Results indicated that after the first injection pair (saline, cocaine) the HiS and LoS groups did not differ (saline vs. cocaine) in locomotor activity; however, after cocaine injections 1, 5 and 6, HiS females were more active than HiS males and LoS females. There were also significant phenotype differences (HiS > LoS) in locomotor activity after cocaine injections 5 and 6. There was only a weak sensitization effect in cocaine-induced locomotor activity in HiS females after cocaine injection 5 (compared to 1); however it was not present after injection 6 or in other groups. The lack of a strong sensitization effect under these temporal and dose conditions was inconsistent with previous reports. However, the results showing HiS > LoS and females > males on cocaine-induced activity measures are consistent with several measures of cocaine-seeking behavior (acquisition, maintenance, escalation, extinction, and reinstatement), and they suggest that cocaine-induced locomotor activity and sensitization are behavioral markers of drug-seeking phenotypes. PMID:17707494

  7. Panic disorder and locomotor activity

    PubMed Central

    Sakamoto, Noriyuki; Yoshiuchi, Kazuhiro; Kikuchi, Hiroe; Takimoto, Yoshiyuki; Kaiya, Hisanobu; Kumano, Hiroaki; Yamamoto, Yoshiharu; Akabayashi, Akira

    2008-01-01

    Background Panic disorder is one of the anxiety disorders, and anxiety is associated with some locomotor activity changes such as "restlessness". However, there have been few studies on locomotor activity in panic disorder using actigraphy, although many studies on other psychiatric disorders have been reported using actigraphy. Therefore, the aim of the present study was to investigate the relationship between panic disorder and locomotor activity pattern using a wrist-worn activity monitor. In addition, an ecological momentary assessment technique was used to record panic attacks in natural settings. Methods Sixteen patients with panic disorder were asked to wear a watch-type computer as an electronic diary for recording panic attacks for two weeks. In addition, locomotor activity was measured and recorded continuously in an accelerometer equipped in the watch-type computer. Locomotor activity data were analyzed using double cosinor analysis to calculate mesor and the amplitude and acrophase of each of the circadian rhythm and 12-hour harmonic component. Correlations between panic disorder symptoms and locomotor activity were investigated. Results There were significant positive correlations between the frequency of panic attacks and mesor calculated from double cosinor analysis of locomotor activity (r = 0.55) and between HAM-A scores and mesor calculated from double cosinor analysis of locomotor activity (r = 0.62). Conclusion Panic disorder patients with more panic attacks and more anxiety have greater objectively assessed locomotor activity, which may reflect the "restlessness" of anxiety disorders. PMID:19017383

  8. Locomotor therapy in neurorehabilitation.

    PubMed

    Hesse, S

    2001-01-01

    Gait rehabilitation is a major aspect of neurological rehabilitation. This review is on locomotor therapy by treadmill stimulation with partial body weight support evolving as a very promising treatment concept over the last years. It enables severely affected patients the repetitive practice of complex gait cycles and thus follows modern aspects of motor learning favoring a task-specific approach. Several studies have shown its potential in patients after stroke, spinal cord injury, M. Parkinson and cerebral palsy. An electromechanical gait trainer relieving the strenuous effort of the therapists and controlling the trunk in a phase-dependent manner is a new alternative.

  9. The rise of novelty in ecosystems.

    PubMed

    Radeloff, Volker C; Williams, John W; Bateman, Brooke L; Burke, Kevin D; Carter, Sarah K; Childress, Evan S; Cromwell, Kara J; Gratton, Claudio; Hasley, Andrew O; Kraemer, Benjamin M; Latzka, Alexander W; Marin-Spiotta, Erika; Meine, Curt D; Munoz, Samuel E; Neeson, Thomas M; Pidgeon, Anna M; Rissman, Adena R; Rivera, Ricardo J; Szymanski, Laura M; Usinowicz, Jacob

    2015-12-01

    Rapid and ongoing change creates novelty in ecosystems everywhere, both when comparing contemporary systems to their historical baselines, and predicted future systems to the present. However, the level of novelty varies greatly among places. Here we propose a formal and quantifiable definition of abiotic and biotic novelty in ecosystems, map abiotic novelty globally, and discuss the implications of novelty for the science of ecology and for biodiversity conservation. We define novelty as the degree of dissimilarity of a system, measured in one or more dimensions relative to a reference baseline, usually defined as either the present or a time window in the past. In this conceptualization, novelty varies in degree, it is multidimensional, can be measured, and requires a temporal and spatial reference. This definition moves beyond prior categorical definitions of novel ecosystems, and does not include human agency, self-perpetuation, or irreversibility as criteria. Our global assessment of novelty was based on abiotic factors (temperature, precipitation, and nitrogen deposition) plus human population, and shows that there are already large areas with high novelty today relative to the early 20th century, and that there will even be more such areas by 2050. Interestingly, the places that are most novel are often not the places where absolute changes are largest; highlighting that novelty is inherently different from change. For the ecological sciences, highly novel ecosystems present new opportunities to test ecological theories, but also challenge the predictive ability of ecological models and their validation. For biodiversity conservation, increasing novelty presents some opportunities, but largely challenges. Conservation action is necessary along the entire continuum of novelty, by redoubling efforts to protect areas where novelty is low, identifying conservation opportunities where novelty is high, developing flexible yet strong regulations and policies, and

  10. Polyploidy and novelty: Gottlieb's legacy

    PubMed Central

    Soltis, Pamela S.; Liu, Xiaoxian; Marchant, D. Blaine; Visger, Clayton J.; Soltis, Douglas E.

    2014-01-01

    Nearly four decades ago, Roose & Gottlieb (Roose & Gottlieb 1976 Evolution 30, 818–830. (doi:10.2307/2407821)) showed that the recently derived allotetraploids Tragopogon mirus and T. miscellus combined the allozyme profiles of their diploid parents (T. dubius and T. porrifolius, and T. dubius and T. pratensis, respectively). This classic paper addressed the link between genotype and biochemical phenotype and documented enzyme additivity in allopolyploids. Perhaps more important than their model of additivity, however, was their demonstration of novelty at the biochemical level. Enzyme multiplicity—the production of novel enzyme forms in the allopolyploids—can provide an extensive array of polymorphism for a polyploid individual and may explain, for example, the expanded ranges of polyploids relative to their diploid progenitors. In this paper, we extend the concept of evolutionary novelty in allopolyploids to a range of genetic and ecological features. We observe that the dynamic nature of polyploid genomes—with alterations in gene content, gene number, gene arrangement, gene expression and transposon activity—may generate sufficient novelty that every individual in a polyploid population or species may be unique. Whereas certain combinations of these features will undoubtedly be maladaptive, some unique combinations of newly generated variation may provide tremendous evolutionary potential and adaptive capabilities. PMID:24958924

  11. Altered object-in-place recognition memory, prepulse inhibition, and locomotor activity in the offspring of rats exposed to a viral mimetic during pregnancy.

    PubMed

    Howland, J G; Cazakoff, B N; Zhang, Y

    2012-01-10

    Infection during pregnancy (i.e., prenatal infection) increases the risk of psychiatric illnesses such as schizophrenia and autism in the adult offspring. The present experiments examined the effects of prenatal immune challenge on behavior in three paradigms relevant to these disorders: prepulse inhibition (PPI) of the acoustic startle response, locomotor responses to an unfamiliar environment and the N-methyl-d-aspartate antagonist MK-801, and three forms of recognition memory. Pregnant Long-Evans rats were exposed to the viral mimetic polyinosinic-polycytidylic acid (PolyI:C; 4 mg/kg, i.v.) on gestational day 15. Offspring were tested for PPI and locomotor activity before puberty (postnatal days (PNDs)35 and 36) and during young adulthood (PNDs 56 and 57). Four prepulse-pulse intervals (30, 50, 80, and 140 ms) were employed in the PPI test. Recognition memory testing was performed using three different spontaneous novelty recognition tests (object, object location, and object-in-place recognition) after PND 60. Regardless of sex, offspring of PolyI:C-treated dams showed disrupted PPI at 50-, 80-, and 140-ms prepulse-pulse intervals. In the prepubescent rats, we observed prepulse facilitation for the 30-ms prepulse-pulse interval trials that was selectively retained in the adult PolyI:C-treated offspring. Locomotor responses to MK-801 were significantly reduced before puberty, whereas responses to an unfamiliar environment were increased in young adulthood. Both male and female PolyI:C-treated offspring showed intact object and object location recognition memory, whereas male PolyI:C-treated offspring displayed significantly impaired object-in-place recognition memory. Females were unable to perform the object-in-place test. The present results demonstrate that prenatal immune challenge during mid/late gestation disrupts PPI and locomotor behavior. In addition, the selective impairment of object-in-place recognition memory suggests tasks that depend on prefrontal

  12. Two separate, but interacting, neural systems for familiarity and novelty detection: a dual-route mechanism.

    PubMed

    Kafkas, Alexandros; Montaldi, Daniela

    2014-05-01

    It has long been assumed that familiarity- and novelty-related processes fall on a single continuum drawing on the same cognitive and neural mechanisms. The possibility that familiarity and novelty processing involve distinct neural networks was explored in a functional magnetic resonance imaging study (fMRI), in which familiarity and novelty judgments were made in contexts emphasizing either familiarity or novelty decisions. Parametrically modulated BOLD responses to familiarity and novelty strength were isolated in two separate, nonoverlapping brain networks. The novelty system involved brain regions along the ventral visual stream, the hippocampus, and the perirhinal and parahippocampal cortices. The familiarity system, on the other hand, involved the dorsomedial thalamic nucleus, and regions within the medial prefrontal cortex and the medial and lateral parietal cortex. Convergence of the two networks, treating familiarity and novelty as a single continuum was only found in a fronto-parietal network. Finally, the orbitomedial prefrontal cortex was found to be sensitive to reported strength/confidence, irrespective of stimulus' familiarity or novelty. This pattern of results suggests a dual-route mechanism supported by the existence of two distinct but interacting functional systems for familiarity and novelty. Overall, these findings challenge current assumptions regarding the neural systems that support the processing of novel and familiar information, and have important implications for research into the neural bases of recognition memory.

  13. The anatomy and physiology of the locomotor system.

    PubMed

    Farley, Alistair; McLafferty, Ella; Hendry, Charles

    Mobilisation is one of the activities of living. The term locomotor system refers to those body tissues and organs responsible for movement. Nurses and healthcare workers should be familiar with the body structures that enable mobilisation to assist those in their care with this activity. This article outlines the structure and function of the locomotor system, including the skeleton, joints, muscles and muscle attachments. Two common bone disorders, osteoporosis and osteoarthritis, are also considered.

  14. Novelty Seeking as a Phenotypic Marker of Adolescent Substance Use

    PubMed Central

    Bidwell, L Cinnamon; Knopik, Valerie S; Audrain-McGovern, Janet; Glynn, Tiffany R; Spillane, Nichea S; Ray, Lara A; Riggs, Nathaniel R; Guillot, Casey R; Pang, Raina D; Leventhal, Adam M

    2015-01-01

    Trait novelty seeking has been consistently implicated in substance use, yet the origins and mechanisms of novelty seeking in substance use proneness are unclear. We aimed to characterize novelty seeking as a phenotypic marker of substance use proneness in adolescence, a critical period for drug use experimentation. To this end, we parsed novelty seeking’s two constituent subdimensions – exploratory excitability (drive for novel experience) and impulsiveness (careless decision-making) – and explored the individual relations of these dimensions to: (1) the use of a variety of licit and illicit substances, (2) family history of substance use, and (3) subjective drug effects. Five hundred eighty five adolescents (mean age = 14.5 years) completed surveys of key variables. Results indicated that, when accounting for the covariation among exploratory excitability and impulsiveness, impulsiveness emerged as the more salient correlate of substance use and was independently associated with initiation of nearly all drug classes. Mediation analyses of the mechanisms of novelty seeking-related risk illustrated that impulsiveness mediated the association of family history of substance use with both initiation and past 30-day frequency of use. Both impulsiveness and exploratory excitability were associated with increased positive and negative subjective drug effects, and the analyses supported a significant indirect pathway from impulsiveness to a more frequent use via positive subjective effects. Although limited by a cross-sectional design, these findings suggest that impulsiveness-like aspects of the novelty seeking construct may represent a useful phenotypic marker for early substance use proneness that potentially (1) increases initiation risk, (2) has familial origins, and (3) promotes more frequent use by altering subjective drug response. PMID:26106262

  15. Locomotor adaptations of some gelatinous zooplankton.

    PubMed

    Bone, Q

    1985-01-01

    Swimming behaviour and locomotor adaptations are described in chaetognaths, larvacean tunicates, some cnidaria, and thaliacean tunicates. The first two groups swim by oscillating a flattened tail, the others by jet propulsion. In chaetognaths, the locomotor muscle fibres are extensively coupled and relatively sparsely innervated, they exhibit compound spike-like potentials. The motoneurons controlling the rhythmic activity of the locomotor muscle lie in a ventral ganglion whose organization is briefly described. Rhythmic swimming bursts in larvaceans are similarly driven by a caudal ganglion near the base of the tail, but each caudal muscle cell is separately innervated by two sets of motor nerves, as well as being coupled to its neighbours. The external epithelium is excitable, and linked to the caudal ganglion by the axons of central cells. Mechanical stimulation of the epithelium evokes receptor potentials followed by action potentials and by bursts of rapid swimming. The trachyline medusa Aglantha and the small siphonophore Chelophyes also show rapid escape responses; in Aglantha these are driven by a specialized giant axon system lacking in other hydromedusae, and in Chelophyes. Slow swimming in Aglantha apparently involves a second nerve supply to the same muscle sheets used in rapid swimming, whereas in Chelophyes slow swimming results from the activity of the smaller posterior nectophore. Slow swimming in siphonophores is more economical than the rapid responses. In the hydrozoan medusa Polyorchis (as in Chelophyes) action potentials in the locomotor muscle sheet change in shape during swimming bursts, and their duration is related to the size of the medusa; they are not simply triggers of muscular contraction. The two groups of thaliacean tunicates are specialized differently. Doliolum is adapted for single rapid jet pulses (during which it achieves instantaneous velocities of 50 body lengths s-l), whilst salps are adapted for slow continuous swimming. The

  16. Rats classified as low or high cocaine locomotor responders: A unique model involving striatal dopamine transporters that predicts cocaine addiction-like behaviors

    PubMed Central

    Yamamoto, Dorothy J.; Nelson, Anna M.; Mandt, Bruce H.; Larson, Gaynor A.; Rorabaugh, Jacki M.; Ng, Christopher M.C.; Barcomb, Kelsey M.; Richards, Toni L.; Allen, Richard M.; Zahniser, Nancy R.

    2013-01-01

    Individual differences are a hallmark of drug addiction. Here, we describe a rat model based on differential initial responsiveness to low dose cocaine. Despite similar brain cocaine levels, individual outbred Sprague-Dawley rats exhibit markedly different magnitudes of acute cocaine-induced locomotor activity and, thereby, can be classified as low or high cocaine responders (LCRs or HCRs). LCRs and HCRs differ in drug-induced, but not novelty-associated, hyperactivity. LCRs have higher basal numbers of striatal dopamine transporters (DATs) than HCRs and exhibit marginal cocaine inhibition of in vivo DAT activity and cocaine-induced increases in extracellular DA. Importantly, lower initial cocaine response predicts greater locomotor sensitization, conditioned place preference and greater motivation to self-administer cocaine following low dose acquisition. Further, outbred Long-Evans rats classified as LCRs, versus HCRs, are more sensitive to cocaine’s discriminative stimulus effects. Overall, results to date with the LCR/HCR model underscore the contribution of striatal DATs to individual differences in initial cocaine responsiveness and the value of assessing the influence of initial drug response on subsequent expression of addiction-like behaviors. PMID:23850581

  17. Hippocampal Networks Habituate as Novelty Accumulates

    ERIC Educational Resources Information Center

    Murty, Vishnu P.; Ballard, Ian C.; Macduffie, Katherine E.; Krebs, Ruth M.; Adcock, R. Alison

    2013-01-01

    Novelty detection, a critical computation within the medial temporal lobe (MTL) memory system, necessarily depends on prior experience. The current study used functional magnetic resonance imaging (fMRI) in humans to investigate dynamic changes in MTL activation and functional connectivity as experience with novelty accumulates. fMRI data were…

  18. Nomenclatural novelties and notes in Penstemon (Plantaginaceae).

    PubMed

    Freeman, Craig C

    2017-01-01

    Seven nomenclatural novelties in Penstemon (Plantaginaceae) are proposed for taxa that will be included in the forthcoming treatment of the genus in the Flora of North America North of Mexico series. Three additional novelties are made for Mexican taxa outside the flora area. Penstemon xylus A. Nelson is determined to be the correct name for the species heretofore called P. tusharensis N. Holmgren.

  19. Hippocampal Networks Habituate as Novelty Accumulates

    ERIC Educational Resources Information Center

    Murty, Vishnu P.; Ballard, Ian C.; Macduffie, Katherine E.; Krebs, Ruth M.; Adcock, R. Alison

    2013-01-01

    Novelty detection, a critical computation within the medial temporal lobe (MTL) memory system, necessarily depends on prior experience. The current study used functional magnetic resonance imaging (fMRI) in humans to investigate dynamic changes in MTL activation and functional connectivity as experience with novelty accumulates. fMRI data were…

  20. Novelty Seeking in Adulthood: Increases Accompany Decline

    ERIC Educational Resources Information Center

    Reio, Thomas G., Jr.; Choi, Namok

    2004-01-01

    Using stereotypes, researchers have predicted that novelty seeking declines in adulthood. Through this cross-sectional study, the authors revealed that only the external sensational type of novelty seeking declined, whereas the internal sensational and internal and external cognitive types remained stable or increased. A population of 233 adults…

  1. High-novelty-preference rats are predisposed to compulsive cocaine self-administration.

    PubMed

    Belin, David; Berson, Nadège; Balado, Eric; Piazza, Pier Vincenzo; Deroche-Gamonet, Véronique

    2011-02-01

    Sensation/novelty-seeking is amongst the best markers of cocaine addiction in humans. However, its implication in the vulnerability to cocaine addiction is still a matter of debate, as it is unclear whether this trait precedes or follows the development of addiction. Sensation/novelty-seeking trait has been identified in rats on the basis of either novelty-induced locomotor activity (high-responder (HR) trait) or novelty-induced place preference (high-novelty-preference trait (HNP)). HR and HNP traits have been associated with differential sensitivity to psychostimulants. However, it has recently been demonstrated that HR rats do not develop compulsive cocaine self-administration (SA) after protracted exposure to the drug, thereby suggesting that at least one dimension of sensation/novelty seeking in the rat is dissociable from the vulnerability to switch from controlled to compulsive cocaine SA. We therefore investigated whether HNP, as measured as the propensity to choose a new environment in a free choice procedure, as opposed to novelty-induced locomotor activity, predicts the vulnerability to, and the severity of, addiction-like behavior for cocaine. For this, we identified HR/LR rats and HNP/LNP rats before any exposure to cocaine. After 60 days of cocaine SA, each rat was given an addiction score based on three addiction-like behaviors (persistence of responding when the drug is signaled as not available, high breakpoint under progressive ratio schedule and resistance to punishment) that resemble the clinical features of drug addiction, namely inability to refrain from drug seeking, high motivation for the drug and compulsive drug use despite adverse consequences. We show that, as opposed to HR rats, HNP rats represent a sub-population predisposed to compulsive cocaine intake, displaying higher addiction scores than LNP rats. This study thereby provides new insights into the factors predisposing to cocaine addiction, supporting the hypothesis that addiction

  2. High-Novelty-Preference Rats are Predisposed to Compulsive Cocaine Self-administration

    PubMed Central

    Belin, David; Berson, Nadège; Balado, Eric; Piazza, Pier Vincenzo; Deroche-Gamonet, Véronique

    2011-01-01

    Sensation/novelty-seeking is amongst the best markers of cocaine addiction in humans. However, its implication in the vulnerability to cocaine addiction is still a matter of debate, as it is unclear whether this trait precedes or follows the development of addiction. Sensation/novelty-seeking trait has been identified in rats on the basis of either novelty-induced locomotor activity (high-responder (HR) trait) or novelty-induced place preference (high-novelty-preference trait (HNP)). HR and HNP traits have been associated with differential sensitivity to psychostimulants. However, it has recently been demonstrated that HR rats do not develop compulsive cocaine self-administration (SA) after protracted exposure to the drug, thereby suggesting that at least one dimension of sensation/novelty seeking in the rat is dissociable from the vulnerability to switch from controlled to compulsive cocaine SA. We therefore investigated whether HNP, as measured as the propensity to choose a new environment in a free choice procedure, as opposed to novelty-induced locomotor activity, predicts the vulnerability to, and the severity of, addiction-like behavior for cocaine. For this, we identified HR/LR rats and HNP/LNP rats before any exposure to cocaine. After 60 days of cocaine SA, each rat was given an addiction score based on three addiction-like behaviors (persistence of responding when the drug is signaled as not available, high breakpoint under progressive ratio schedule and resistance to punishment) that resemble the clinical features of drug addiction, namely inability to refrain from drug seeking, high motivation for the drug and compulsive drug use despite adverse consequences. We show that, as opposed to HR rats, HNP rats represent a sub-population predisposed to compulsive cocaine intake, displaying higher addiction scores than LNP rats. This study thereby provides new insights into the factors predisposing to cocaine addiction, supporting the hypothesis that addiction

  3. How should novelty be valued in science?

    PubMed

    Cohen, Barak A

    2017-07-25

    Scientists are under increasing pressure to do "novel" research. Here I explore whether there are risks to overemphasizing novelty when deciding what constitutes good science. I review studies from the philosophy of science to help understand how important an explicit emphasis on novelty might be for scientific progress. I also review studies from the sociology of science to anticipate how emphasizing novelty might impact the structure and function of the scientific community. I conclude that placing too much value on novelty could have counterproductive effects on both the rate of progress in science and the organization of the scientific community. I finish by recommending that our current emphasis on novelty be replaced by a renewed emphasis on predictive power as a characteristic of good science.

  4. How should novelty be valued in science?

    PubMed Central

    Cohen, Barak A

    2017-01-01

    Scientists are under increasing pressure to do "novel" research. Here I explore whether there are risks to overemphasizing novelty when deciding what constitutes good science. I review studies from the philosophy of science to help understand how important an explicit emphasis on novelty might be for scientific progress. I also review studies from the sociology of science to anticipate how emphasizing novelty might impact the structure and function of the scientific community. I conclude that placing too much value on novelty could have counterproductive effects on both the rate of progress in science and the organization of the scientific community. I finish by recommending that our current emphasis on novelty be replaced by a renewed emphasis on predictive power as a characteristic of good science. DOI: http://dx.doi.org/10.7554/eLife.28699.001 PMID:28742499

  5. Novelty preference in patients with developmental amnesia.

    PubMed

    Munoz, M; Chadwick, M; Perez-Hernandez, E; Vargha-Khadem, F; Mishkin, M

    2011-12-01

    To re-examine whether or not selective hippocampal damage reduces novelty preference in visual paired comparison (VPC), we presented two different versions of the task to a group of patients with developmental amnesia (DA), each of whom sustained this form of pathology early in life. Compared with normal control participants, the DA group showed a delay-dependent reduction in novelty preference on one version of the task and an overall reduction on both versions combined. Because VPC is widely considered to be a measure of incidental recognition, the results appear to support the view that the hippocampus contributes to recognition memory. A difficulty for this conclusion, however, is that according to one current view the hippocampal contribution to recognition is limited to task conditions that encourage recollection of an item in some associated context, and according to another current view, to recognition of an item with the high confidence judgment that reflects a strong memory. By contrast, VPC, throughout which the participant remains entirely uninstructed other than to view the stimuli, would seem to lack such task conditions and so would likely lead to recognition based on familiarity rather than recollection or, alternatively, weak memories rather than strong. However, before concluding that the VPC impairment therefore contradicts both current views regarding the role of the hippocampus in recognition memory, two possibilities that would resolve this issue need to be investigated. One is that some variable in VPC, such as the extended period of stimulus encoding during familiarization, overrides its incidental nature, and, because this condition promotes either recollection- or strength-based recognition, renders the task hippocampal-dependent. The other possibility is that VPC, rather than providing a measure of incidental recognition, actually assesses an implicit, information-gathering process modulated by habituation, for which the hippocampus is

  6. NOVELTY PREFERENCE IN PATIENTS WITH DEVELOPMENTAL AMNESIA

    PubMed Central

    Munoz, M.; Chadwick, M.; Perez-Hernandez, E; Vargha-Khadem, F.; Mishkin, M.

    2010-01-01

    To re-examine whether or not selective hippocampal damage reduces novelty preference in visual paired comparison (VPC), we presented two different versions of the task to a group of patients with developmental amnesia (DA), each of whom sustained this form of pathology early in life. Compared with normal control participants, the DA group showed a delay-dependent reduction in novelty preference on one version of the task and an overall reduction on both versions combined. Because VPC is widely considered to be a measure of incidental recognition, the results appear to support the view that the hippocampus contributes to recognition memory. A difficulty for this conclusion, however, is that according to one current view the hippocampal contribution to recognition is limited to task conditions that encourage recollection of an item in some associated context, and according to another current view, to recognition of an item with the high confidence judgment that reflects a strong memory. By contrast, VPC, throughout which the participant remains entirely uninstructed other than to view the stimuli, would seem to lack such task conditions and so would likely lead to recognition based on familiarity rather than recollection or, alternatively, weak memories rather than strong. However, before concluding that the VPC impairment therefore contradicts both current views regarding the role of the hippocampus in recognition memory, two possibilities that would resolve this issue need to be investigated. One is that some variable in VPC, such as the extended period of stimulus encoding during familiarization, overrides its incidental nature, and, because this condition promotes either recollection- or strength-based recognition, renders the task hippocampal-dependent. The other possibility is that VPC, rather than providing a measure of incidental recognition, actually assesses an implicit, information-gathering process modulated by habituation, for which the hippocampus is

  7. Cyclical parthenogenesis and viviparity in aphids as evolutionary novelties.

    PubMed

    Davis, Gregory K

    2012-09-01

    Evolutionary novelties represent challenges to biologists, particularly those who would like to understand the developmental and genetic changes responsible for their appearance. Most modern aphids possess two apparent evolutionary novelties: cyclical parthenogenesis (a life cycle with both sexual and asexual phases) and viviparity (internal development and live birth of progeny) in their asexual phase. Here I discuss the evolution of these apparent novelties from a developmental standpoint. Although a full understanding of the evolution of cyclical parthenogenesis and viviparity in aphids can seem a daunting task, these complex transitions can at least be broken down into a handful of steps. I argue that these should include the following: a differentiation of two developmentally distinct oocytes; de novo synthesis of centrosomes and modification of meiosis during asexual oogenesis; a loss or bypass of any cell cycle arrest and changes in key developmental events during viviparous oogenesis; and a change in how mothers specify the sexual vs. asexual fates of their progeny. Grappling with the nature of such steps and the order in which they occurred ought to increase our understanding and reduce the apparent novelty of complex evolutionary transitions.

  8. The role of mesoaccumbens--pallidal circuitry in novelty-induced behavioral activation.

    PubMed

    Hooks, M S; Kalivas, P W

    1995-02-01

    When exposed to an environment for the first time, rats express greater behavioral activation than rats which were previously habituated to that environment. The circuit containing the ventral tegmental area, nucleus accumbens and ventral pallidum is required for the expression of locomotor activity elicited by amphetamine-like psychostimulants. It was hypothesized that this circuit is necessary for the expression of novelty-induced motor activity. Dopamine is a neurotransmitter in the projection from the ventral tegmental area to the nucleus accumbens, while GABA is contained in the projections from the nucleus accumbens to the ventral pallidum and from the ventral pallidum back to the ventral tegmental area. Prior to exposing rats to a novel or habituated environment, they received a microinjection of either saline vehicle or one of the following drugs: fluphenazine (dopamine antagonist) into the nucleus accumbens, muscimol (GABAA agonist) into the ventral pallidum, or baclofen GABAB agonist) into the ventral tegmental area. Each of these pretreatments prevented novelty-induced motor activation without suppressing the activity of habituated animals. In contrast, when these microinjections were made into adjacent motor nuclei of the basal ganglia, including fluphenazine into the striatum, muscimol into the globus pallidus and baclofen into the substantia nigra, they were ineffective in blocking novelty-induced motor activity. These data indicate that the integrity of the circuit that contains the ventral tegmental area, nucleus accumbens and ventral pallidum is required for the manifestation of novelty-induced motor activity.

  9. Is There a Novelty Effect on Student Attitudes Toward Personalized Instruction?

    ERIC Educational Resources Information Center

    Linder, Steve; Whitehurst, Carol

    1973-01-01

    Purpose of study was to investigate the "novelty effect" hypothesis by investigating the relationship of student responses on an attitude survey with the number of personalized courses they were taking concurrently. (Author)

  10. Two Components of Nocturnal Locomotor Suppression by Light

    PubMed Central

    Morin, Lawrence P.; Lituma, Pablo J.; Studholme, Keith M.

    2010-01-01

    In nocturnal rodents, millisecond light (“flash”) stimuli can induce both a large circadian rhythm phase shift and an associated state change from highly active to quiescence followed by behavioral sleep. Suppression of locomotion (“negative masking”) is an easily measured correlate of the state change. The present mouse studies used both flashes and longer light stimuli (“pulses”) to distinguish initiation from maintenance effects of light on locomotor suppression and to determine whether the locomotor suppression exhibits temporal integration as is thought to be characteristic of phase shift responses to pulse, but not flash, stimuli. In Expt. 1, locomotor suppression increased with irradiance (0.01–100 μW/cm2), in accordance with previous reports. It also increased with stimulus duration (3–3000 sec), but interpretation of this result is complicated by the ability of light to both initiate and maintain locomotor suppression. In Expt. 2, an irradiance response curve was determined using a stimulus series of 10 flashes, 2 msec each, with total flash energy varying from 0.0025 – 110.0 J/m2. This included a test for temporal integration in which the effects of two equal energy series of flashes were compared, but which differed in the number of flashes per series (10 vs 100). The 10 flash series more effectively elicited locomotor suppression than the 100 flash series, a result consistent with prior observations involving flash-induced phase shifts. In Expt. 3, exposure of mice to an 11 hr light stimulus yielded irradiance-dependent locomotor suppression that can be maintained for the entire stimulus duration by a 100 μW/cm2 stimulus. Light has the ability to initiate a time-limited (30–40 min) interval of locomotor suppression (initiation effect) that can be extended by additional light (maintenance effect). Temporal integration resembling that seen in phase shifting responses to light does not exist for either phase shift or locomotor

  11. Novelties that change carrying capacity.

    PubMed

    Erwin, Douglas H

    2012-09-01

    Comparative developmental studies have revealed a rich array of details about the patterns and processes of morphological change in animals and increasingly in plants. But, applying these insights to the study of major episodes of evolutionary innovation requires understanding how these novel morphologies become established and sufficiently abundant (either as individuals within a species or as a clade of species) to be preserved in the fossil record, and, in many cases, to influence ecological processes. Evolutionary novelties may: (1) disappear without changing the species; (2) be associated with the generation (through selection or drift) of a new species; and if the latter (3) may or may not become ecologically significant. Only the latter are commonly preserved in the fossil record. These alternatives mirror the distinction among historians of technology between innovation and invention. Here, I argue that specific sorts of evolutionary inventions drive ecological transformation, essentially constructing an environment for themselves and ancillary organisms through ecological spillover effects, increasing the "carrying capacity" of an ecosystem.

  12. Sex differences in locomotor effects of morphine in the rat

    PubMed Central

    Craft, Rebecca M.; Clark, James L.; Hart, Stephen P.; Pinckney, Megan K.

    2007-01-01

    Sex differences in reinforcing, analgesic and other effects of opioids have been demonstrated; however, the extent to which sex differences in motoric effects of opioids contribute to apparent sex differences in their primary effects is not known. The goal of this study was to compare the effects of the prototypic mu opioid agonist morphine on locomotor activity in male vs. female rats. Saline or morphine (1-10 mg/kg) was administered s.c. to adult Sprague-Dawley rats, which were placed into a photobeam apparatus for 3-5 hr to measure activity. Modulation of morphine's effects by gonadal hormones and by handling (either during the test session or for 4 days before the test session) were examined. Morphine initially suppressed and later increased locomotor activity in both sexes relative to their saline-injected controls, but males were more sensitive than females to the initial locomotor suppressant effect of morphine. Intermittent, brief handling during the 3-hr test session blunted morphine-induced locomotor activation in both sexes. Females in proestrus were the most sensitive to morphine's locomotor-stimulant effect, with females in estrus showing the least response to morphine. Gonadectomized (GDX) males with or without testosterone were equally sensitive to morphine's effects, whereas GDX females treated with estradiol showed a blunted response to morphine's effects, similar to intact females in estrus. Brief handling on each of 4 consecutive days pre-test attenuated morphine's locomotor suppressant effect in males but had no effect in females, thereby eliminating the sex difference. These data suggest that sex differences in morphine's effects on locomotor activity can be attributed to gonadal hormones in females, and to differential stress-induced modulation of morphine's effects in males vs. females. PMID:17217999

  13. Homology, homoplasy, novelty, and behavior.

    PubMed

    Hall, Brian K

    2013-01-01

    Richard Owen coined the modern definition of homology in 1843. Owen's conception of homology was pre-evolutionary, nontransformative (homology maintained basic plans or archetypes), and applied to the fully formed structures of animals. I sketch out the transition to an evolutionary approach to homology in which all classes of similarity are interpreted against the single branching tree of life, and outline the evidence for the application of homology across all levels and features of the biological hierarchy, including behavior. Owen contrasted homology with analogy. While this is not incorrect it is a pre-evolutionary contrast. Lankester [Lankester [1870] Journal of Natural History, 6 (31), 34-43] proposed homoplasy as the class of homology applicable to features formed by independent evolution. Today we identify homology, convergence, parallelism, and novelties as patterns of evolutionary change. A central issue in homology [Owen [1843] Lectures on comparative anatomy and physiology of the invertebrate animals, delivered at the Royal College of Surgeons in 1843. London: Longman, Brown, Green & Longmans] has been whether homology of features-the "same" portion of the brain in different species, for example-depends upon those features sharing common developmental pathways. Owen did not require this criterion, although he observed that homologues often do share developmental pathways (and we now know, often share gene pathways). A similar situation has been explored in the study of behavior, especially whether behaviors must share a common structural, developmental, neural, or genetic basis to be classified as homologous. However, and importantly, development and genes evolve. As shown with both theory and examples, morphological and behavioral features of the phenotype can be homologized as structural or behavioral homologues, respectively, even when their developmental or genetic bases differ (are not homologous). Copyright © 2012 Wiley Periodicals, Inc.

  14. Nomenclatural novelties and notes in Penstemon (Plantaginaceae)

    PubMed Central

    Freeman, Craig C.

    2017-01-01

    Abstract Seven nomenclatural novelties in Penstemon (Plantaginaceae) are proposed for taxa that will be included in the forthcoming treatment of the genus in the Flora of North America North of Mexico series. Three additional novelties are made for Mexican taxa outside the flora area. Penstemon xylus A. Nelson is determined to be the correct name for the species heretofore called P. tusharensis N. Holmgren. PMID:28781556

  15. Conceptualizing evolutionary novelty: moving beyond definitional debates.

    PubMed

    Brigandt, Ingo; Love, Alan C

    2012-09-01

    According to many biologists, explaining the evolution of morphological novelty and behavioral innovation are central endeavors in contemporary evolutionary biology. These endeavors are inherently multidisciplinary but also have involved a high degree of controversy. One key source of controversy is the definitional diversity associated with the concept of evolutionary novelty, which can lead to contradictory claims (a novel trait according to one definition is not a novel trait according to another). We argue that this diversity should be interpreted in light of a different epistemic role played by the concept of evolutionary novelty-the structuring of a problem space or setting of an explanatory agenda-rather than the concept's capacity to categorize traits as novel. This distinctive role is consistent with the definitional diversity and shows that the concept of novelty benefits ongoing investigation by focusing attention on answering different questions related to comprehending the origins of novelty. A review of recent theoretical and empirical work on evolutionary novelty confirms this interpretation.

  16. Novelty, coherence, and Mendeleev's periodic table.

    PubMed

    Schindler, Samuel

    2014-03-01

    Predictivism is the view that successful predictions of "novel" evidence carry more confirmational weight than accommodations of already known evidence. Novelty, in this context, has traditionally been conceived of as temporal novelty. However temporal predictivism has been criticized for lacking a rationale: why should the time order of theory and evidence matter? Instead, it has been proposed, novelty should be construed in terms of use-novelty, according to which evidence is novel if it was not used in the construction of a theory. Only if evidence is use-novel can it fully support the theory entailing it. As I point out in this paper, the writings of the most influential proponent of use-novelty contain a weaker and a stronger version of use-novelty. However both versions, I argue, are problematic. With regard to the appraisal of Mendeleev' periodic table, the most contentious historical case in the predictivism debate, I argue that temporal predictivism is indeed supported, although in ways not previously appreciated. On the basis of this case, I argue for a form of so-called symptomatic predictivism according to which temporally novel predictions carry more confirmational weight only insofar as they reveal the theory's presumed coherence of facts as real.

  17. Exendin-4 Decreases Amphetamine-induced Locomotor Activity

    PubMed Central

    Erreger, Kevin; Davis, Adeola R.; Poe, Amanda M.; Greig, Nigel H.; Stanwood, Gregg D.; Galli, Aurelio

    2012-01-01

    Glucagon-like peptide-1 (GLP-1) is released in response to nutrient ingestion and is a regulator of energy metabolism and consummatory behaviors through both peripheral and central mechanisms. The GLP-1 receptor (GLP-1R) is widely distributed in the central nervous system, however little is known about how GLP-1Rs regulate ambulatory behavior. The abused psychostimulant amphetamine (AMPH) promotes behavioral locomotor activity primarily by inducing the release of the neurotransmitter dopamine. Here, we identify the GLP-1R agonist exendin-4 (Ex-4) as a modulator of behavioral activation by AMPH. We report that in rats a single acute administration of Ex-4 decreases both basal locomotor activity as well as AMPH-induced locomotor activity. Ex-4 did not induce behavioral responses reflecting anxiety or aversion. Our findings implicate GLP-1R signaling as a novel modulator of psychostimulant-induced behavior and therefore a potential therapeutic target for psychostimulant abuse. PMID:22465309

  18. Movement Exploration and Locomotor Skills.

    ERIC Educational Resources Information Center

    National Center on Educational Media and Materials for the Handicapped, Columbus, OH.

    Selected from the National Instructional Materials Information System (NIMIS)--a computer based on-line interactive retrieval system on special education materials--the bibliography covers 23 materials for teaching movement exploration and locomotor skills to handicapped students at all educational levels. Entries are presented in order of NIMIS…

  19. Locomotor training improves premotoneuronal control after chronic spinal cord injury.

    PubMed

    Knikou, Maria; Mummidisetty, Chaithanya K

    2014-06-01

    Spinal inhibition is significantly reduced after spinal cord injury (SCI) in humans. In this work, we examined if locomotor training can improve spinal inhibition exerted at a presynaptic level. Sixteen people with chronic SCI received an average of 45 training sessions, 5 days/wk, 1 h/day. The soleus H-reflex depression in response to low-frequency stimulation, presynaptic inhibition of soleus Ia afferent terminals following stimulation of the common peroneal nerve, and bilateral EMG recovery patterns were assessed before and after locomotor training. The soleus H reflexes evoked at 1.0, 0.33, 0.20, 0.14, and 0.11 Hz were normalized to the H reflex evoked at 0.09 Hz. Conditioned H reflexes were normalized to the associated unconditioned H reflex evoked with subjects seated, while during stepping both H reflexes were normalized to the maximal M wave evoked after the test H reflex at each bin of the step cycle. Locomotor training potentiated homosynaptic depression in all participants regardless the type of the SCI. Presynaptic facilitation of soleus Ia afferents remained unaltered in motor complete SCI patients. In motor incomplete SCIs, locomotor training either reduced presynaptic facilitation or replaced presynaptic facilitation with presynaptic inhibition at rest. During stepping, presynaptic inhibition was modulated in a phase-dependent manner. Locomotor training changed the amplitude of locomotor EMG excitability, promoted intralimb and interlimb coordination, and altered cocontraction between knee and ankle antagonistic muscles differently in the more impaired leg compared with the less impaired leg. The results provide strong evidence that locomotor training improves premotoneuronal control after SCI in humans at rest and during walking. Copyright © 2014 the American Physiological Society.

  20. Locomotor adaptability in persons with unilateral transtibial amputation.

    PubMed

    Darter, Benjamin J; Bastian, Amy J; Wolf, Erik J; Husson, Elizabeth M; Labrecque, Bethany A; Hendershot, Brad D

    2017-01-01

    Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb.

  1. Locomotor adaptability in persons with unilateral transtibial amputation

    PubMed Central

    Bastian, Amy J.; Wolf, Erik J.; Husson, Elizabeth M.; Labrecque, Bethany A.; Hendershot, Brad D.

    2017-01-01

    Background Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb. PMID:28704467

  2. Effects of Sodium Butyrate on Methamphetamine-Sensitized Locomotor Activity

    PubMed Central

    Harkness, John H.; Hitzemann, Robert J.; Edmunds, Stephanie; Phillips, Tamara J.

    2012-01-01

    Neuroadaptations associated with behavioral sensitization induced by repeated exposure to methamphetamine (MA) appear to be involved in compulsive drug pursuit and use. Increased histone acetylation, an epigenetic effect resulting in altered gene expression, may promote sensitized responses to psychostimulants. The role of histone acetylation in the expression and acquisition of MA-induced locomotor sensitization was examined by measuring the effect of histone deacetylase inhibition by sodium butyrate (NaB). For the effect on expression, vehicle or NaB (630 mg/kg, intraperitoneally) was administered 30 min prior to MA challenge in mice treated repeatedly with MA (10 days of 2 mg/kg MA) or saline (10 days), and then locomotor response to MA challenge was measured. NaB treatment increased the locomotor response to MA in both acutely MA treated and sensitized animals. For acquisition, NaB was administered 30 min prior to each MA exposure (10 days of 1 or 2 mg/kg), but not prior to the MA challenge test. Treatment with NaB during the sensitization acquisition period significantly increased locomotor activation by MA in sensitized mice only. NaB alone did not significantly alter locomotor activity. Acute NaB or MA, but not the combination, appeared to increase striatal acetylation at histone H4. Repeated treatment with MA, but not NaB or MA plus NaB, increased striatal acetylation at histone H3. Although increased histone acetylation may alter the expression of genes involved in acute locomotor response to MA and in the acquisition of MA-induced sensitization, results for acetylation at H3 and H4 showed little correspondence with behavior. PMID:23137698

  3. A circuit-based mechanism underlying familiarity signaling and the preference for novelty.

    PubMed

    Molas, Susanna; Zhao-Shea, Rubing; Liu, Liwang; DeGroot, Steven R; Gardner, Paul D; Tapper, Andrew R

    2017-09-01

    Novelty preference (NP) is an evolutionarily conserved, essential survival mechanism often dysregulated in neuropsychiatric disorders. NP is mediated by a motivational dopamine signal that increases in response to novel stimuli, thereby driving exploration. However, the mechanism by which once-novel stimuli transition to familiar stimuli is unknown. Here we describe a neuroanatomical substrate for familiarity signaling, the interpeduncular nucleus (IPN) of the midbrain, which is activated as novel stimuli become familiar with multiple exposures. In mice, optogenetic silencing of IPN neurons increases salience of and interaction with familiar stimuli without affecting novelty responses, whereas photoactivation of the same neurons reduces exploration of novel stimuli mimicking familiarity. Bidirectional control of NP by the IPN depends on familiarity signals and novelty signals arising from excitatory habenula and dopaminergic ventral tegmentum inputs, which activate and reduce IPN activity, respectively. These results demonstrate that familiarity signals through unique IPN circuitry that opposes novelty seeking to control NP.

  4. On the origins of novelty in development and evolution.

    PubMed

    Moczek, Armin P

    2008-05-01

    The origin of novel traits is what draws many to evolutionary biology, yet our understanding of the mechanisms that underlie the genesis of novelty remains limited. Here I review definitions of novelty including its relationship to homology. I then discuss how ontogenetic perspectives may allow us to move beyond current roadblocks in our understanding of the mechanics of innovation. Specifically, I explore the roles of canalization, plasticity and threshold responses during development in generating a reservoir of cryptic genetic variation free to drift and accumulate in natural populations. Environmental or genetic perturbations that exceed the buffering capacity of development can then release this variation, and, through evolution by genetic accommodation, result in rapid diversification, recurrence of lost phenotypes as well as the origins of novel features. I conclude that, in our quest to understand the nature of innovation, the nature of development deserves to take center stage.

  5. Deconstructing locomotor networks with experimental injury to define their membership.

    PubMed

    Nistri, Andrea; Taccola, Giuliano; Mladinic, Miranda; Margaryan, Gayane; Kuzhandaivel, Anujaianthi

    2010-06-01

    Although spinal injury is a major cause of chronic disability, the mechanisms responsible for the lesion pathophysiology and their dynamic evolution remain poorly understood. Hence, current treatments aimed at blocking damage extension are unsatisfactory. To unravel the acute spinal injury processes, we have developed a model of the neonatal rat spinal cord in vitro subjected to kainate-evoked excitotoxicity or metabolic perturbation (hypoxia, aglycemia, and free oxygen radicals) or their combination. The study outcome is fictive locomotion one day after the lesion and its relation to histological damage. Excitotoxicity always suppresses locomotor network activity and produces large gray matter damage, while network bursting persists supported by average survival of nearly half premotoneurons and motoneurons. Conversely, metabolic perturbation simply depresses locomotor network activity as damage mainly concerns white rather than gray matter. Coapplication of kainate and metabolic perturbation completely eliminates locomotor network activity. These results indicate distinct cellular targets for excitotoxic versus dysmetabolic damage with differential consequences on locomotor pattern formation. Furthermore, these data enable to estimate the minimal network membership compatible with expression of locomotor activity.

  6. Quaternary naltrexone reverses radiogenic and morphine-induced locomotor hyperactivity

    SciTech Connect

    Mickley, G.A.; Stevens, K.E.; Galbraith, J.A.; White, G.A.; Gibbs, G.L.

    1984-04-01

    The present study attempted to determine the relative role of the peripheral and central nervous system in the production of morphine-induced or radiation-induced locomotor hyperactivity of the mouse. Toward this end, we used a quaternary derivative of an opiate antagonist (naltrexone methobromide), which presumably does not cross the blood-brain barrier. Quaternary naltrexone was used to challenge the stereotypic locomotor response observed in these mice after either an i.p. injection of morphine or exposure to 1500 rads /sup 60/Co. The quaternary derivative of naltrexone reversed the locomotor hyperactivity normally observed in the C57BL/6J mouse after an injection of morphine. It also significantly attenuated radiation-induced locomotion. The data reported here support the hypothesis of endorphin involvement in radiation-induced and radiogenic behaviors. However, these conclusions are contingent upon further research which more fully evaluates naltrexone methobromide's capacity to cross the blood-brain barrier.

  7. Quantifying Conceptual Novelty in the Biomedical Literature.

    PubMed

    Mishra, Shubhanshu; Torvik, Vetle I

    2016-01-01

    We introduce several measures of novelty for a scientific article in MEDLINE based on the temporal profiles of its assigned Medical Subject Headings (MeSH). First, temporal profiles for all MeSH terms (and pairs of MeSH terms) were characterized empirically and modelled as logistic growth curves. Second, a paper's novelty is captured by its youngest MeSH (and pairs of MeSH) as measured in years and volume of prior work. Across all papers in MEDLINE published since 1985, we find that individual concept novelty is rare (2.7% of papers have a MeSH ≤ 3 years old; 1.0% have a MeSH ≤ 20 papers old), while combinatorial novelty is the norm (68% have a pair of MeSH ≤ 3 years old; 90% have a pair of MeSH ≤ 10 papers old). Furthermore, these novelty measures exhibit complex correlations with article impact (as measured by citations received) and authors' professional age.

  8. Quantifying Conceptual Novelty in the Biomedical Literature

    PubMed Central

    Mishra, Shubhanshu; Torvik, Vetle I.

    2016-01-01

    We introduce several measures of novelty for a scientific article in MEDLINE based on the temporal profiles of its assigned Medical Subject Headings (MeSH). First, temporal profiles for all MeSH terms (and pairs of MeSH terms) were characterized empirically and modelled as logistic growth curves. Second, a paper's novelty is captured by its youngest MeSH (and pairs of MeSH) as measured in years and volume of prior work. Across all papers in MEDLINE published since 1985, we find that individual concept novelty is rare (2.7% of papers have a MeSH ≤ 3 years old; 1.0% have a MeSH ≤ 20 papers old), while combinatorial novelty is the norm (68% have a pair of MeSH ≤ 3 years old; 90% have a pair of MeSH ≤ 10 papers old). Furthermore, these novelty measures exhibit complex correlations with article impact (as measured by citations received) and authors' professional age. PMID:27942200

  9. Reward Motivation Accelerates the Onset of Neural Novelty Signals in Humans to 85 Milliseconds

    PubMed Central

    Bunzeck, Nico; Doeller, Christian F.; Fuentemilla, Lluis; Dolan, Raymond J.; Duzel, Emrah

    2009-01-01

    Summary The neural responses that distinguish novel from familiar items in recognition memory tasks are remarkably fast in both humans and nonhuman primates. In humans, the earliest onsets of neural novelty effects emerge at about ∼150–200 ms after stimulus onset [1–5]. However, in recognition memory studies with nonhuman primates, novelty effects can arise at as early as 70–80 ms [6, 7]. Here, we address the possibility that this large species difference in onset latencies is caused experimentally by the necessity of using reward reinforcement to motivate the detection of novel or familiar items in nonhuman primates but not in humans. Via magnetoencephalography in humans, we show in two experiments that the onset of neural novelty signals is accelerated from ∼200 ms to ∼85 ms if correct recognition memory for either novel or familiar items is rewarded. Importantly, this acceleration is independent of whether the detection of the novel or the familiar scenes is rewarded. Furthermore, this early novelty effect contributed to memory retrieval because neural reward responses, which were contingent upon novelty detection, followed ∼100 ms later. Thus, under the contextual influence of reward motivation, behaviorally relevant novelty signals emerge much faster than previously held possible in humans. PMID:19576774

  10. Novel and Direct Access to the Human Locomotor Spinal Circuitry

    PubMed Central

    Gerasimenko, Yury; Gorodnichev, Ruslan; Machueva, Ekaterina; Pivovarova, Elena; Semyenov, Denis; Savochin, Alexandr; Roy, Roland R.; Edgerton, V. Reggie

    2010-01-01

    The degree of automaticity of locomotion in primates compared to other mammals remains unclear. Here we examine the possibility for activation of the spinal locomotor circuitry in non-injured humans by spinal electromagnetic stimulation (SEMS). SEMS (3 Hz and 1.3 to 1.82 Tesla) at the T11–T12 vertebrae induced involuntary bilateral locomotor-like movements in the legs of individuals placed in a gravity-neutral position. The formation of locomotor-like activity during SEMS started with a latency of 0.68 ± 0.1 sec after delivering the first stimulus, unlike continuous vibration of muscles that requires several seconds. The first EMG burst in response to SEMS was observed most often in a proximal flexor muscle. We speculate that SEMS directly activates the circuitry intrinsic to the spinal cord, as suggested by the immediate response and the electrophysiological observations demonstrating an absence of strictly time-linked responses within the EMG burst associated with individual stimuli during SEMS. SEMS in the presence of vibration of the leg muscles was more effective in facilitating locomotor-like activity than SEMS alone. The present results suggest that SEMS could be an effective noninvasive clinical tool to determine the potential of an individual to recover locomotion after a spinal cord injury as well as being an effective rehabilitation tool itself. PMID:20220003

  11. Novel and direct access to the human locomotor spinal circuitry.

    PubMed

    Gerasimenko, Yury; Gorodnichev, Ruslan; Machueva, Ekaterina; Pivovarova, Elena; Semyenov, Denis; Savochin, Alexandr; Roy, Roland R; Edgerton, V Reggie

    2010-03-10

    The degree of automaticity of locomotion in primates compared with other mammals remains unclear. Here, we examine the possibility for activation of the spinal locomotor circuitry in noninjured humans by spinal electromagnetic stimulation (SEMS). SEMS (3 Hz and 1.3-1.82 tesla) at the T11-T12 vertebrae induced involuntary bilateral locomotor-like movements in the legs of individuals placed in a gravity-neutral position. The formation of locomotor-like activity during SEMS started with a latency of 0.68 +/- 0.1 s after delivering the first stimulus, unlike continuous vibration of muscles, which requires several seconds. The first EMG burst in response to SEMS was observed most often in a proximal flexor muscle. We speculate that SEMS directly activates the circuitry intrinsic to the spinal cord, as suggested by the immediate response and the electrophysiological observations demonstrating an absence of strictly time-linked responses within the EMG burst associated with individual stimuli during SEMS. SEMS in the presence of vibration of the leg muscles was more effective in facilitating locomotor-like activity than SEMS alone. The present results suggest that SEMS could be an effective noninvasive clinical tool to determine the potential of an individual to recover locomotion after a spinal cord injury, as well as being an effective rehabilitation tool itself.

  12. Resonator memories and optical novelty filters

    NASA Astrophysics Data System (ADS)

    Anderson, Dana Z.; Erle, Marie C.

    Optical resonators having holographic elements are potential candidates for storing information that can be accessed through content addressable or associative recall. Closely related to the resonator memory is the optical novelty filter, which can detect the differences between a test object and a set of reference objects. We discuss implementations of these devices using continuous optical media such as photorefractive materials. The discussion is framed in the context of neural network models. There are both formal and qualitative similarities between the resonator memory and optical novelty filter and network models. Mode competition arises in the theory of the resonator memory, much as it does in some network models. We show that the role of the phenomena of "daydreaming" in the real-time programmable optical resonator is very much akin to the role of "unlearning" in neural network memories. The theory of programming the real-time memory for a single mode is given in detail. This leads to a discussion of the optical novelty filter. Experimental results for the resonator memory, the real-time programmable memory, and the optical tracking novelty filter are reviewed. We also point to several issues that need to be addressed in order to implement more formal models of neural networks.

  13. Acute restraint stress and corticosterone transiently disrupts novelty preference in an object recognition task.

    PubMed

    Vargas-López, Viviana; Torres-Berrio, Angélica; González-Martínez, Lina; Múnera, Alejandro; Lamprea, Marisol R

    2015-09-15

    The object recognition task is a procedure based on rodents' natural tendency to explore novel objects which is frequently used for memory testing. However, in some instances novelty preference is replaced by familiarity preference, raising questions regarding the validity of novelty preference as a pure recognition memory index. Acute stress- and corticosterone administration-induced novel object preference disruption has been frequently interpreted as memory impairment; however, it is still not clear whether such effect can be actually attributed to either mnemonic disruption or altered novelty seeking. Seventy-five adult male Wistar rats were trained in an object recognition task and subjected to either acute stress or corticosterone administration to evaluate the effect of stress or corticosterone on an object recognition task. Acute stress was induced by restraining movement for 1 or 4h, ending 30 min before the sample trial. Corticosterone was injected intraperitoneally 10 min before the test trial which was performed either 1 or 24h after the sample trial. Four-hour, but not 1-h, stress induced familiar object preference during the test trial performed 1h after the sample trial; however, acute stress had no effects on the test when performed 24h after sample trial. Systemic administration of corticosterone before the test trial performed either 1 or 24h after the sample trial also resulted in familiar object preference. However, neither acute stress nor corticosterone induced changes in locomotor behaviour. Taken together, such results suggested that acute stress probably does not induce memory retrieval impairment but, instead, induces an emotional arousing state which motivates novelty avoidance.

  14. Locomotor Expertise Predicts Infants' Perseverative Errors

    ERIC Educational Resources Information Center

    Berger, Sarah E.

    2010-01-01

    This research examined the development of inhibition in a locomotor context. In a within-subjects design, infants received high- and low-demand locomotor A-not-B tasks. In Experiment 1, walking 13-month-old infants followed an indirect path to a goal. In a control condition, infants took a direct route. In Experiment 2, crawling and walking…

  15. Novelty Detection in and Between Different Modalities

    SciTech Connect

    Veflingstad, Henning; Yildirim, Sule

    2008-01-21

    Our general aim is to reflect the advances in artificial intelligence and cognitive science fields to space exploration studies such that next generation space rovers can benefit from these advances. We believe next generation space rovers can benefit from the studies related to employing conceptual representations in generating structured thought. This way, rovers need not be equipped with all necessary steps of an action plan to execute in space exploration but they can autonomously form representations of their world and reason on them to make intelligent decision. As part of this approach, autonomous novelty detection is an important feature of next generation space rovers. This feature allows a rover to make further decisions about exploring a rock sample more closely or not and on its own. This way, a rover will use less of its time for communication between the earth and itself and more of its time for achieving its assigned tasks in space. In this paper, we propose an artificial neural network based novelty detection mechanism that next generation space rovers can employ as part of their intelligence. We also present an implementation of such a mechanism and present its reliability in detecting novelty.

  16. Exploration, novelty, surprise, and free energy minimization.

    PubMed

    Schwartenbeck, Philipp; Fitzgerald, Thomas; Dolan, Raymond J; Friston, Karl

    2013-01-01

    This paper reviews recent developments under the free energy principle that introduce a normative perspective on classical economic (utilitarian) decision-making based on (active) Bayesian inference. It has been suggested that the free energy principle precludes novelty and complexity, because it assumes that biological systems-like ourselves-try to minimize the long-term average of surprise to maintain their homeostasis. However, recent formulations show that minimizing surprise leads naturally to concepts such as exploration and novelty bonuses. In this approach, agents infer a policy that minimizes surprise by minimizing the difference (or relative entropy) between likely and desired outcomes, which involves both pursuing the goal-state that has the highest expected utility (often termed "exploitation") and visiting a number of different goal-states ("exploration"). Crucially, the opportunity to visit new states increases the value of the current state. Casting decision-making problems within a variational framework, therefore, predicts that our behavior is governed by both the entropy and expected utility of future states. This dissolves any dialectic between minimizing surprise and exploration or novelty seeking.

  17. Novelty detection for breast cancer image classification

    NASA Astrophysics Data System (ADS)

    Cichosz, Pawel; Jagodziński, Dariusz; Matysiewicz, Mateusz; Neumann, Łukasz; Nowak, Robert M.; Okuniewski, Rafał; Oleszkiewicz, Witold

    2016-09-01

    Using classification learning algorithms for medical applications may require not only refined model creation techniques and careful unbiased model evaluation, but also detecting the risk of misclassification at the time of model application. This is addressed by novelty detection, which identifies instances for which the training set is not sufficiently representative and for which it may be safer to restrain from classification and request a human expert diagnosis. The paper investigates two techniques for isolated instance identification, based on clustering and one-class support vector machines, which represent two different approaches to multidimensional outlier detection. The prediction quality for isolated instances in breast cancer image data is evaluated using the random forest algorithm and found to be substantially inferior to the prediction quality for non-isolated instances. Each of the two techniques is then used to create a novelty detection model which can be combined with a classification model and used at the time of prediction to detect instances for which the latter cannot be reliably applied. Novelty detection is demonstrated to improve random forest prediction quality and argued to deserve further investigation in medical applications.

  18. Integrated Locomotor Function Tests for Countermeasure Evaluation

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Landsness, E. C.; Black, F. O.

    2005-01-01

    Following spaceflight crewmembers experience locomotor dysfunction due to inflight adaptive alterations in sensorimotor function. Countermeasures designed to mitigate these postflight gait alterations need to be assessed with a new generation of tests that evaluate the interaction of various sensorimotor sub-systems central to locomotor control. The goal of the present study was to develop new functional tests of locomotor control that could be used to test the efficacy of countermeasures. These tests were designed to simultaneously examine the function of multiple sensorimotor systems underlying the control of locomotion and be operationally relevant to the astronaut population. Traditionally, gaze stabilization has been studied almost exclusively in seated subjects performing target acquisition tasks requiring only the involvement of coordinated eye-head movements. However, activities like walking involve full-body movement and require coordination between lower limbs and the eye-head-trunk complex to achieve stabilized gaze during locomotion. Therefore the first goal of this study was to determine how the multiple, interdependent, full-body sensorimotor gaze stabilization subsystems are functionally coordinated during locomotion. In an earlier study we investigated how alteration in gaze tasking changes full-body locomotor control strategies. Subjects walked on a treadmill and either focused on a central point target or read numeral characters. We measured: temporal parameters of gait, full body sagittal plane segmental kinematics of the head, trunk, thigh, shank and foot, accelerations along the vertical axis at the head and the shank, and the vertical forces acting on the support surface. In comparison to the point target fixation condition, the results of the number reading task showed that compensatory head pitch movements increased, peak head acceleration was reduced and knee flexion at heel-strike was increased. In a more recent study we investigated the

  19. Goal-dependent modulation of declarative memory: neural correlates of temporal recency decisions and novelty detection.

    PubMed

    Dudukovic, Nicole M; Wagner, Anthony D

    2007-06-18

    Declarative memory allows an organism to discriminate between previously encountered and novel items, and to place past encounters in time. Numerous imaging studies have investigated the neural processes supporting item recognition, whereas few have examined retrieval of temporal information. In the present study, functional magnetic resonance imaging (fMRI) was conducted while subjects engaged in temporal recency and item novelty decisions. Subjects encountered three-alternative forced-choice retrieval trials, each consisting of two words from a preceding study phase and one novel word, and were instructed to either identify the novel item (Novelty trials) or the more recently presented study item (Recency trials). Relative to correct Novelty decisions, correct Recency decisions elicited greater activation in a network of left-lateralized regions, including frontopolar and dorsolateral prefrontal cortex and intraparietal sulcus. A conjunction analysis revealed that these left-lateralized regions overlapped with those previously observed to be engaged during source recollection versus novelty detection, suggesting that during Recency trials subjects attempted to recollect event details. Consistent with this interpretation, correct Recency decisions activated posterior hippocampus and parahippocampal cortex, whereas incorrect Recency decisions elicited greater anterior cingulate activation. The magnitude of this latter effect positively correlated with activation in right dorsolateral prefrontal cortex. Finally, correct Novelty decisions activated the anterior medial temporal lobe to a greater extent than did correct Recency decisions, suggesting that medial temporal novelty responses are not obligatory but rather can be modulated by the goal-directed allocation of attention. Collectively, these findings advance understanding of how subjects strategically engage frontal and parietal mechanisms in the service of attempting to remember the temporal order of events

  20. Novelty enhances visual salience independently of reward in the parietal lobe.

    PubMed

    Foley, Nicholas C; Jangraw, David C; Peck, Christopher; Gottlieb, Jacqueline

    2014-06-04

    Novelty modulates sensory and reward processes, but it remains unknown how these effects interact, i.e., how the visual effects of novelty are related to its motivational effects. A widespread hypothesis, based on findings that novelty activates reward-related structures, is that all the effects of novelty are explained in terms of reward. According to this idea, a novel stimulus is by default assigned high reward value and hence high salience, but this salience rapidly decreases if the stimulus signals a negative outcome. Here we show that, contrary to this idea, novelty affects visual salience in the monkey lateral intraparietal area (LIP) in ways that are independent of expected reward. Monkeys viewed peripheral visual cues that were novel or familiar (received few or many exposures) and predicted whether the trial will have a positive or a negative outcome--i.e., end in a reward or a lack of reward. We used a saccade-based assay to detect whether the cues automatically attracted or repelled attention from their visual field location. We show that salience--measured in saccades and LIP responses--was enhanced by both novelty and positive reward associations, but these factors were dissociable and habituated on different timescales. The monkeys rapidly recognized that a novel stimulus signaled a negative outcome (and withheld anticipatory licking within the first few presentations), but the salience of that stimulus remained high for multiple subsequent presentations. Therefore, novelty can provide an intrinsic bonus for attention that extends beyond the first presentation and is independent of physical rewards. Copyright © 2014 the authors 0270-6474/14/347947-11$15.00/0.

  1. Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton.

    PubMed

    Gordon, Keith E; Kinnaird, Catherine R; Ferris, Daniel P

    2013-04-01

    Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to "fight" the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations.

  2. Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton

    PubMed Central

    Kinnaird, Catherine R.; Ferris, Daniel P.

    2013-01-01

    Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to “fight” the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations. PMID:23307949

  3. Models of neural novelty detectors, with similarities to cerebral cortex.

    PubMed

    Salu, Y

    1988-01-01

    A novelty detector is a functional unit, that indicates whether an incoming stimulus is familiar or novel. Novelty detection is prevalent in the central nervous system (CNS), and is involved in various activities. Its basic characteristics are discussed first. Then, models of neural novelty detectors are described, and tested and evaluated in simulations. The simulations have shown that one novelty detector, the bi-compartmental, simulates very closely the behavior of neural novelty detectors. This model is constructed in a way that resembles the observed architecture and function of area 17, and similar regions in the cortex. The first step in novelty detection is data retrieval. The proposed novelty detectors can utilize various compatible modes of data storage and retrieval, and one of those has been utilized in the simulations.

  4. Lipidomics and H218O labeling techniques reveal increased remodeling of DHA-containing membrane phospholipids associated with abnormal locomotor responses in α-tocopherol deficient zebrafish (danio rerio) embryos

    PubMed Central

    McDougall, Melissa Q.; Choi, Jaewoo; Stevens, Jan F.; Truong, Lisa; Tanguay, Robert L.; Traber, Maret G.

    2016-01-01

    We hypothesized that vitamin E (α-tocopherol) is required by the developing embryonic brain to prevent depletion of highly polyunsaturated fatty acids, especially docosahexaenoic acid (DHA, 22:6), the loss of which we predicted would underlie abnormal morphological and behavioral outcomes. Therefore, we fed adult 5D zebrafish (Danio rerio) defined diets without (E−) or with added α-tocopherol (E+, 500 mg RRR-α-tocopheryl acetate/kg diet) for a minimum of 80 days, and then spawned them to obtain E− and E+ embryos. The E− compared with E+ embryos were 82% less responsive (p<0.01) to a light/dark stimulus at 96 h post-fertilization (hpf), demonstrating impaired locomotor behavior, even in the absence of gross morphological defects. Evaluation of phospholipid (PL) and lysophospholipid (lyso-PL) composition using untargeted lipidomics in E− compared with E+ embryos at 24, 48, 72, and 120 hpf showed that four PLs and three lyso-PLs containing docosahexaenoic acid (DHA), including lysophosphatidylcholine (LPC 22:6, required for transport of DHA into the brain, p<0.001), were at lower concentrations in E− at all time-points. Additionally, H218O labeling experiments revealed enhanced turnover of LPC 22:6 (p<0.001) and three other DHA-containing PLs in the E− compared with the E+ embryos, suggesting that increased membrane remodeling is a result of PL depletion. Together, these data indicate that α-tocopherol deficiency in the zebrafish embryo causes the specific depletion and increased turnover of DHA-containing PL and lyso-PLs, which may compromise DHA delivery to the brain and thereby contribute to the functional impairments observed in E− embryos. PMID:26774753

  5. C57BL/6J MICE EXHIBIT REDUCED DOPAMINE D3 RECEPTOR-MEDIATED LOCOMOTOR-INHIBITORY FUNCTION RELATIVE TO DBA/2J MICE

    PubMed Central

    McNAMARA, R. K.; LEVANT, B.; TAYLOR, B.; AHLBRAND, R.; LIU, Y.; SULLIVAN, J. R.; STANFORD, K.; RICHTAND, N. M.

    2007-01-01

    Previous reports have identified greater sensitivity to the locomotor-stimulating, sensitizing, and reinforcing effects of amphetamine in inbred C57BL/6J mice relative to inbred DBA/2J mice. The dopamine D3 receptor (D3R) plays an inhibitory role in the regulation of rodent locomotor activity, and exerts inhibitory opposition to D1 receptor (D1R)-mediated signaling. Based on these observations, we investigated D3R expression and D3R-mediated locomotor-inhibitory function, as well as D1R binding and D1R-mediated locomotor-stimulating function, in C57BL/6J and DBA/2J mice. C57BL/6J mice exhibited lower D3R binding density (−32%) in the ventral striatum (nucleus accumbens/islands of Calleja), lower D3R mRNA expression (−26%) in the substantia nigra/ventral tegmentum, and greater D3R mRNA expression (+40%) in the hippocampus, relative to DBA/2J mice. There were no strain differences in DR3 mRNA expression in the ventral striatum or prefrontal cortex, nor were there differences in D1R binding in the ventral striatum. Behaviorally, C57BL/6J mice were less sensitive to the locomotor-inhibitory effect of the D3R agonist PD128907 (10 μg/kg), and more sensitive to the locomotor-stimulating effects of novelty, amphetamine (1 mg/kg), and the D1R-like agonist ±-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8,-diol hydrochloride (SKF38393) (5–20 mg/kg) than DBA/2J mice. While the selective D3R antagonist N-(4-[4-{2,3-dichlorphenyl}-1 piperazinyl]butyl)-2-fluorenylcarboxamide (NGB 2904) (0.01–1.0 mg/kg) augmented novelty-, amphetamine-, and SKF38393-induced locomotor activity in DBA/2J mice, it reduced novelty-induced locomotor activity in C57BL/6J mice. Collectively, these results demonstrate that C57BL/6J mice exhibit less D3R-mediated inhibitory function relative to DBA/2J mice, and suggest that reduced D3R-mediated inhibitory function may contribute to heightened sensitivity to the locomotor-stimulating effects of amphetamine in the C57BL/6J mouse strain

  6. Apathy, Novelty Processing, and the P3 Potential in Parkinson’s Disease

    PubMed Central

    Kaufman, David A. S.; Bowers, Dawn; Okun, Michael S.; Van Patten, Ryan; Perlstein, William M.

    2016-01-01

    Parkinson’s disease (PD) is characterized by deficits in goal-directed behavior as well as mood and motivational symptoms, including apathy, depression, and anxiety. The present study investigated novelty processing in PD, using event-related potentials (ERPs) to characterize electrophysiological reflections of visual novelty processing. Since apathy has been associated with decreased novelty processing (P3 potentials) in highly apathetic PD patients, we were particularly interested to see if this relationship exists in a sample of PD patients with heterogeneous levels of apathy. Non-demented patients with PD receiving dopaminergic treatment (n = 14) and healthy control participants (n = 12) completed a three-stimulus oddball task while EEG was recorded. Relative to controls, the PD patients exhibited reductions in centrofrontally distributed P3 potentials when viewing novel distracters during this task. Distracter-related P3 amplitudes evoked by novel distracters were strongly associated with apathy symptoms, even after controlling for the effects of depression, anxiety, and executive function. Executive dysfunction was also predictive of novelty-related P3 processing, yet this relationship was independent from that of apathy. These findings suggest that the brain’s electrophysiological response to novelty is closely related to both motivational and cognitive symptoms in PD, even for patients whose apathy symptoms are not excessive. These results have significant implications for our understanding of non-motor symptoms in this clinical population. PMID:27445962

  7. Apathy, Novelty Processing, and the P3 Potential in Parkinson's Disease.

    PubMed

    Kaufman, David A S; Bowers, Dawn; Okun, Michael S; Van Patten, Ryan; Perlstein, William M

    2016-01-01

    Parkinson's disease (PD) is characterized by deficits in goal-directed behavior as well as mood and motivational symptoms, including apathy, depression, and anxiety. The present study investigated novelty processing in PD, using event-related potentials (ERPs) to characterize electrophysiological reflections of visual novelty processing. Since apathy has been associated with decreased novelty processing (P3 potentials) in highly apathetic PD patients, we were particularly interested to see if this relationship exists in a sample of PD patients with heterogeneous levels of apathy. Non-demented patients with PD receiving dopaminergic treatment (n = 14) and healthy control participants (n = 12) completed a three-stimulus oddball task while EEG was recorded. Relative to controls, the PD patients exhibited reductions in centrofrontally distributed P3 potentials when viewing novel distracters during this task. Distracter-related P3 amplitudes evoked by novel distracters were strongly associated with apathy symptoms, even after controlling for the effects of depression, anxiety, and executive function. Executive dysfunction was also predictive of novelty-related P3 processing, yet this relationship was independent from that of apathy. These findings suggest that the brain's electrophysiological response to novelty is closely related to both motivational and cognitive symptoms in PD, even for patients whose apathy symptoms are not excessive. These results have significant implications for our understanding of non-motor symptoms in this clinical population.

  8. [Novelty of vital dyes in ophthalmic surgery].

    PubMed

    Rejdak, Robert; Oleszczuk, Agnieszka; Mańkowska, Anna; Kiczyńska, Magdalena; Zagórski, Zbigniew; Zarnowski, Tomasz

    2010-01-01

    The aim of this paper is to present recent developments in the area of novelty of vital dyes in intraocular surgery. The authors present the advantages and disadvantages of several vital dyes currently used in ophthalmic surgery. Vital dyes are used to allow better intraoperative visualization of both the anterior and posterior segments. Indocyanine green and trypan blue are the most frequently used and the most efficacious dyes for staining the important anatomic areas but often are associated with significant side effects. These dyes are used in cataract and vitreo-retinal surgery. Other dyes including rhodamine 6G, E68, bromophenol blue, light green and Chicago blue are still under preclinical assessment.

  9. [Contributions and novelties from Functional Analytic Psychotherapy].

    PubMed

    Ferro García, Rafael; Valero Aguayo, Luis; López Bermúdez, Miguel A

    2007-08-01

    Functional Analytic Psychotherapy is based on the principles of radical behaviourism. It emphasises the impact of events occurring during therapeutic sessions, the therapist-client interaction context, functional equivalence of environments, natural reinforcement, and shaping by the therapist. Functional Analytic Psychotherapy makes use of both the basic principles of behaviour analysis: individual functional assessment and application of in vivo treatment. This paper analyses novelties and new contributions of this therapy. New contributions are classified in various categories: integration with other psychotherapies, improvement of therapeutic skills, methods for evaluation and data recording in therapy, its application to several clinical problems, and studies of its efficacy.

  10. Visual Habituation and Preference for Novelty in Five-Week-Old Infants.

    ERIC Educational Resources Information Center

    Hunter, Michael A.; Ames, Elinor W.

    This study was designed to determine if the failure of previous investigations to find habituation and response to novelty in infants younger than 2 months of age was because the stimuli used were too complex or because a constant number of trials rather than an individual criterion of habituation was used. A total of 24 infants between 5 and 6…

  11. Dynamics and plasticity of spinal locomotor circuits.

    PubMed

    El Manira, Abdeljabbar

    2014-12-01

    Spinal circuits generate coordinated locomotor movements. These hardwired circuits are supplemented with neuromodulation that provide the necessary flexibility for animals to move smoothly through their environment. This review will highlight some recent insights gained in understanding the functional dynamics and plasticity of the locomotor circuits. First the mechanisms governing the modulation of the speed of locomotion will be discussed. Second, advantages of the modular organization of the locomotor networks with multiple circuits engaged in a task-dependent manner will be examined. Finally, the neuromodulation and the resulting plasticity of the locomotor circuits will be summarized with an emphasis on endocannabinoids and nitric oxide. The intention is to extract general principles of organization and discuss some onto-genetic and phylogenetic divergences.

  12. Repeatability of locomotor performance and morphology-locomotor performance relationships.

    PubMed

    Conradsen, Cara; Walker, Jeffrey A; Perna, Catherine; McGuigan, Katrina

    2016-09-15

    There is good evidence that natural selection drives the evolution of locomotor performance, but the processes that generate the among-individual variation for selection to act on are relatively poorly understood. We measured prolonged swimming performance, Ucrit, and morphology in a large cohort (n=461) of wild-type zebrafish (Danio rerio) at ∼6 months and again at ∼9 months. Using mixed-model analyses to estimate repeatability as the intraclass correlation coefficient, we determined that Ucrit was significantly repeatable (r=0.55; 95% CI: 0.45-0.64). Performance differences between the sexes (males 12% faster than females) and changes with age (decreasing 0.07% per day) both contributed to variation in Ucrit and, therefore, the repeatability estimate. Accounting for mean differences between sexes within the model decreased the estimate of Ucrit repeatability to 21% below the naïve estimate, while fitting age in the models increased the estimate to 14% above the naïve estimate. Greater consideration of factors such as age and sex is therefore necessary for the interpretation of performance repeatability in wild populations. Body shape significantly predicted Ucrit in both sexes in both assays, with the morphology-performance relationship significantly repeatable at the population level. However, morphology was more strongly predicative of performance in older fish, suggesting a change in the contribution of morphology relative to other factors such as physiology and behaviour. The morphology-performance relationship changed with age to a greater extent in males than females.

  13. Acts of kindness and acts of novelty affect life satisfaction.

    PubMed

    Buchanan, Kathryn E; Bardi, Anat

    2010-01-01

    The present experiment was designed to establish the effects of acts of kindness and acts of novelty on life satisfaction. Participants aged 18-60 took part on a voluntary basis. They were randomly assigned to perform either acts of kindness, acts of novelty, or no acts on a daily basis for 10 days. Their life satisfaction was measured before and after the 10-day experiment. As expected, performing acts of kindness or acts of novelty resulted in an increase in life satisfaction.

  14. Organization of mammalian locomotor rhythm and pattern generation

    PubMed Central

    McCrea, David A.; Rybak, Ilya A.

    2008-01-01

    Central pattern generators (CPGs) located in the spinal cord produce the coordinated activation of flexor and extensor motoneurons during locomotion. Previously proposed architectures for the spinal locomotor CPG have included the classical half-center oscillator and the unit burst generator (UBG) comprised of multiple coupled oscillators. We have recently proposed another organization in which a two-level CPG has a common rhythm generator (RG) that controls the operation of the pattern formation (PF) circuitry responsible for motoneuron activation. These architectures are discussed in relation to recent data obtained during fictive locomotion in the decerebrate cat. The data show that the CPG can maintain the period and phase of locomotor oscillations both during spontaneous deletions of motoneuron activity and during sensory stimulation affecting motoneuron activity throughout the limb. The proposed two-level CPG organization has been investigated with a computational model which incorporates interactions between the CPG, spinal circuits and afferent inputs. The model includes interacting populations of spinal interneurons and motoneurons modeled in the Hodgkin-Huxley style. Our simulations demonstrate that a relatively simple CPG with separate RG and PF networks can realistically reproduce many experimental phenomena including spontaneous deletions of motoneuron activity and a variety of effects of afferent stimulation. The model suggests plausible explanations for a number of features of real CPG operation that would be difficult to explain in the framework of the classical single-level CPG organization. Some modeling predictions and directions for further studies of locomotor CPG organization are discussed. PMID:17936363

  15. Clinical Application Of Advanced Infrared Thermography (IRT) In Locomotor Diseases

    NASA Astrophysics Data System (ADS)

    Engel, Joachim-Michael

    1983-11-01

    Locomotor diseases is a wide range of about 450 different illnesses with all different pathologies, clinical and prognostic features and response to treatment. No single method will be able to cover the whole spectrum of local and systemic signs and symptoms. Nevertheless there is a need for objective measurements at the site of disease: clinical examination is often enough depending from subjective estimations and personal experiance of the clinician. Laboratory tests only show the systemic effect of the disease, like inflammation. X-rays are restricted to the detection of structural changes appearing late during the pathological process, even when using different techniques. Here IRT offers several advantages to the clinician as well as to the patient. As a non invasive method it monitors the course of disease at the anatomic site of pathology. Quantitative figures calculated from the thermogram,either taken at steady-state or during dynamic tests, are essential for differential diagnosis and follow-up. Advanced IRT camera systems fulfill all requirements set up for medical thermography recently by the National Bureau of Standards. Although, the user should check his system daily with regard to precision of absolute temperature measurements. Standardisation of recording technique is essential as well,to get reliable results. Ambient conditions must be adapted to the locomotor disease pathology under study. Advanced IRT systems , e.g. ZEISS-IKOTHERM, together with image processing capability and special software, e.g. THERMOTOM package, are valuable tools to the rheumatologist for diagnosing and monitoring locomotor diseases.

  16. Locomotor development of zebrafish (Danio rerio) under novel hydrodynamic conditions.

    PubMed

    Danos, Nicole

    2012-02-01

    The kinematics, neuromuscular control, and hydrodynamic aspects of normal locomotor activity in larval zebrafish have been extensively studied. Although locomotion depends heavily on the fluid properties of water, we have little knowledge of what sensory and developmental cues zebrafish larvae receive from their interaction with the fluid medium in which they grow. In this study, I manipulate the viscosity of water in which larvae grow until 5 and 7 days postfertilization (dpf) and record the kinematics of routine turns in their growth medium. Larvae are then transferred to a new medium of different viscosity and filmed again after short and long acclimation periods. Four hypotheses are tested: (1) larval kinematics are constrained by muscle activation patterns, (2) larval kinematics are guided by kinematic objectives, (3) routine turning control is independent of early locomotor experience, and (4) response to novel fluid environment is independent of developmental stage. The results indicate that a kinematic parameter, stage 1 angle, correlates with the kinematics of stage 1 while muscle activation patterns likely constrain stage 2. Development of this behavior is not dependent on locomotor experience both at 5 and 7 dpf, although the two age groups respond differently to increased viscosity. © 2012 WILEY PERIODICALS, INC.

  17. Inhibitory Role of Inducible cAMP Early Repressor (ICER) in Methamphetamine-Induced Locomotor Sensitization

    PubMed Central

    Han, Wenhua; Takamatsu, Yukio; Yamamoto, Hideko; Kasai, Shinya; Endo, Shogo; Shirao, Tomoaki; Kojima, Nobuhiko; Ikeda, Kazutaka

    2011-01-01

    Background The inducible cyclic adenosine monophosphate (cAMP) early repressor (ICER) is highly expressed in the central nervous system and functions as a repressor of cAMP response element-binding protein (CREB) transcription. The present study sought to clarify the role of ICER in the effects of methamphetamine (METH). Methods and Findings We tested METH-induced locomotor sensitization in wildtype mice, ICER knockout mice, and ICER I-overexpressing mice. Both ICER wildtype mice and knockout mice displayed increased locomotor activity after continuous injections of METH. However, ICER knockout mice displayed a tendency toward higher locomotor activity compared with wildtype mice, although no significant difference was observed between the two genotypes. Moreover, compared with wildtype mice, ICER I-overexpressing mice displayed a significant decrease in METH-induced locomotor sensitization. Furthermore, Western blot analysis and quantitative real-time reverse transcription polymerase chain reaction demonstrated that ICER overexpression abolished the METH-induced increase in CREB expression and repressed cocaine- and amphetamine-regulated transcript (CART) and prodynorphin (Pdyn) expression in mice. The decreased CART and Pdyn mRNA expression levels in vivo may underlie the inhibitory role of ICER in METH-induced locomotor sensitization. Conclusions Our data suggest that ICER plays an inhibitory role in METH-induced locomotor sensitization. PMID:21738744

  18. Caffeine and amphetamine produce cross-sensitization to nicotine-induced locomotor activity in mice.

    PubMed

    Celik, Eylem; Uzbay, I Tayfun; Karakas, Sirel

    2006-01-01

    Sensitization development is linked to the addictive potential of the drugs. The same mechanisms might play a role in sensitization development to the different addictive drugs. The aim of the study was to investigate the development of cross-sensitization to caffeine and amphetamine in nicotine-induced locomotor sensitization in mice. Caffeine (2.5-20 mg/kg), amphetamine (1-16 mg/kg) or saline were injected to Swiss-Webster mice and locomotor activity was recorded for 30 min. Nicotine (0.5-2 mg/kg) or saline were injected to mice and locomotor activity was recorded for 30 min. Process was applied for 19 days, every other day (10 sessions). Caffeine (5 mg/kg), amphetamine (4 mg/kg) or saline were challenged to the different groups of nicotine-sensitized mice 2 days later on the last nicotine injection, and locomotor activity was recorded. Repetitive injections of nicotine (0.5-2 mg) produced locomotor sensitization in mice. After caffeine and amphetamine challenge injections, locomotor activity of the nicotine-sensitized mice was found to be significantly higher than saline-pretreated mice. Saline challenge did not produce any significant effect in nicotine- or saline-pretreated mice. Our results suggest that a cross-sensitization developed to both caffeine and amphetamine in nicotine-sensitized mice. In conclusion, similar central mechanisms may be responsible for the development of addiction to these substances.

  19. Increased Amygdala and Visual Cortex Activity and Functional Connectivity towards Stimulus Novelty Is Associated with State Anxiety

    PubMed Central

    Ousdal, Olga T.; Andreassen, Ole A.; Server, Andres; Jensen, Jimmy

    2014-01-01

    Novel stimuli often require a rapid reallocation of sensory processing resources to determine the significance of the event, and the appropriate behavioral response. Both the amygdala and the visual cortex are central elements of the neural circuitry responding to novelty, demonstrating increased activity to new as compared to highly familiarized stimuli. Further, these brain areas are intimately connected, and thus the amygdala may be a key region for directing sensory processing resources to novel events. Although knowledge regarding the neurocircuit of novelty detection is gradually increasing, we still lack a basic understanding of the conditions that are necessary and sufficient for novelty-specific responses in human amygdala and the visual cortices, and if these brain areas interact during detection of novelty. In the present study, we investigated the response of amygdala and the visual cortex to novelty, by comparing functional MRI activity between 1st and 2nd time presentation of a series of emotional faces in an event-related task. We observed a significant decrease in amygdala and visual cortex activity already after a single stimulus exposure. Interestingly, this decrease in responsiveness was less for subjects with a high score on state anxiety. Further, novel faces stimuli were associated with a relative increase in the functional coupling between the amygdala and the inferior occipital gyrus (BA 18). Thus, we suggest that amygdala is involved in fast sensory boosting that may be important for attention reallocation to novel events, and that the strength of this response depends on individual state anxiety. PMID:24755617

  20. Locomotor expertise predicts infants' perseverative errors.

    PubMed

    Berger, Sarah E

    2010-03-01

    This research examined the development of inhibition in a locomotor context. In a within-subjects design, infants received high- and low-demand locomotor A-not-B tasks. In Experiment 1, walking 13-month-old infants followed an indirect path to a goal. In a control condition, infants took a direct route. In Experiment 2, crawling and walking 13-month-old infants crawled through a tunnel to reach a goal at the other end and received the same control condition as in Experiment 1. In both experiments, perseverative errors occurred more often in the high-demand condition than in the low-demand condition. Moreover, in Experiment 2, walkers perseverated more than crawlers, and extent of perseveration was related to infants' locomotor experience. In Experiment 3, the authors addressed a possible confound in Experiment 2 between locomotor expertise and locomotor posture. Novice crawlers perseverated in the difficult tunnels condition, behaving more like novice walkers than expert crawlers. As predicted by a cognitive capacity account of infant perseveration, overtaxed attentional resources resulted in a cognition-action trade-off. Experts who found the task less motorically effortful than novices had more cognitive resources available for problem solving.

  1. Redundancy and Novelty Mining in the Business Blogosphere

    ERIC Educational Resources Information Center

    Tsai, Flora S.; Chan, Kap Luk

    2010-01-01

    Purpose: The paper aims to explore the performance of redundancy and novelty mining in the business blogosphere, which has not been studied before. Design/methodology/approach: Novelty mining techniques are implemented to single out novel information out of a massive set of text documents. This paper adopted the mixed metric approach which…

  2. The Novelty Exploration Bonus and Its Attentional Modulation

    ERIC Educational Resources Information Center

    Krebs, Ruth M.; Schott, Bjorn H.; Schutze, Hartmut; Duzel, Emrah

    2009-01-01

    We hypothesized that novel stimuli represent salient learning signals that can motivate "exploration" in search for potential rewards. In computational theories of reinforcement learning, this is referred to as the novelty "exploration bonus" for rewards. If true, stimulus novelty should enhance the reward anticipation signals in brain areas that…

  3. Redundancy and Novelty Mining in the Business Blogosphere

    ERIC Educational Resources Information Center

    Tsai, Flora S.; Chan, Kap Luk

    2010-01-01

    Purpose: The paper aims to explore the performance of redundancy and novelty mining in the business blogosphere, which has not been studied before. Design/methodology/approach: Novelty mining techniques are implemented to single out novel information out of a massive set of text documents. This paper adopted the mixed metric approach which…

  4. The Novelty Exploration Bonus and Its Attentional Modulation

    ERIC Educational Resources Information Center

    Krebs, Ruth M.; Schott, Bjorn H.; Schutze, Hartmut; Duzel, Emrah

    2009-01-01

    We hypothesized that novel stimuli represent salient learning signals that can motivate "exploration" in search for potential rewards. In computational theories of reinforcement learning, this is referred to as the novelty "exploration bonus" for rewards. If true, stimulus novelty should enhance the reward anticipation signals in brain areas that…

  5. Tree shrews (Tupaia belangeri) exhibit novelty preference in the novel location memory task with 24-h retention periods

    PubMed Central

    Nair, Jayakrishnan; Topka, Marlene; Khani, Abbas; Isenschmid, Manuela; Rainer, Gregor

    2014-01-01

    Novelty preference is pervasive in mammalian species, and describes an inherent tendency to preferentially explore novelty. The novel location memory task studied here assesses the ability of animals to form accurate memories of a spatial configuration, consisting of several identical objects placed within an arena. Tree shrews were first familiarized with a particular object configuration during several sessions, and then an object was displaced during a test session. Tree shrews exhibited enhanced exploration when confronted with this novel configuration. The most reliable indicator associated with novelty preference was an enhancement in directed exploration towards the novel object, although we also observed a non-specific overall increase in exploration in one experiment. During the test session, we also observed an exploration of the location, which had previously been occupied by the displaced object, an effect termed empty quadrant. Our behavioral findings suggest multiple stages of spatial memory formation in tree shrews that are associated with various forms of behavioral responses to novelty. Reduced novelty preference has been linked to major depressive disorder in human patients. Given the established social conflict depression model in tree shrews, we anticipate that the study of the neural circuits of novelty preference and their malfunction during depression may have implications for understanding or treating depression in humans. PMID:24782805

  6. Tree shrews (Tupaia belangeri) exhibit novelty preference in the novel location memory task with 24-h retention periods.

    PubMed

    Nair, Jayakrishnan; Topka, Marlene; Khani, Abbas; Isenschmid, Manuela; Rainer, Gregor

    2014-01-01

    Novelty preference is pervasive in mammalian species, and describes an inherent tendency to preferentially explore novelty. The novel location memory task studied here assesses the ability of animals to form accurate memories of a spatial configuration, consisting of several identical objects placed within an arena. Tree shrews were first familiarized with a particular object configuration during several sessions, and then an object was displaced during a test session. Tree shrews exhibited enhanced exploration when confronted with this novel configuration. The most reliable indicator associated with novelty preference was an enhancement in directed exploration towards the novel object, although we also observed a non-specific overall increase in exploration in one experiment. During the test session, we also observed an exploration of the location, which had previously been occupied by the displaced object, an effect termed empty quadrant. Our behavioral findings suggest multiple stages of spatial memory formation in tree shrews that are associated with various forms of behavioral responses to novelty. Reduced novelty preference has been linked to major depressive disorder in human patients. Given the established social conflict depression model in tree shrews, we anticipate that the study of the neural circuits of novelty preference and their malfunction during depression may have implications for understanding or treating depression in humans.

  7. Shifting gears in hippocampus: temporal dissociation between familiarity and novelty signatures in a single event.

    PubMed

    Ben-Yakov, Aya; Rubinson, Mica; Dudai, Yadin

    2014-09-24

    The hippocampus is known to be involved in encoding and retrieval of episodes. However, real-life experiences are expected to involve both encoding and retrieval, and it is unclear how the human hippocampus subserves both functions in the course of a single event. We presented participants with brief movie clips multiple times and examined the effect of familiarity on the hippocampal response at event onset versus event offset. Increased familiarity resulted in a decreased offset response, indicating that the offset response is a novelty-related signature. The magnitude of this offset response was correlated, across hippocampal voxels, with an independent measure of successful encoding, based on nonrepeated clips. This suggests that the attenuated offset response to familiar clips reflects reduced encoding. In addition, the posterior hippocampus exhibited an increased onset response to familiar events, switching from an online familiarity signal to an offline novelty signal during a single event. Moreover, participants with stronger memory exhibited increased reactivation of online activity during familiar events, in line with a retrieval signature. Our results reveal a spatiotemporal dissociation between novelty/encoding and familiarity/retrieval signatures, assumed to reflect different computational modes, in response to the same stimulus.

  8. Effects of novelty and methamphetamine on conditioned and sensory reinforcement.

    PubMed

    Lloyd, David R; Kausch, Michael A; Gancarz, Amy M; Beyley, Linda J; Richards, Jerry B

    2012-10-01

    Light onset can be both a sensory reinforcer (SR) with intrinsic reinforcing properties, and a conditioned reinforcer (CR) which predicts a biologically important reinforcer. Stimulant drugs, such as methamphetamine (METH), may increase the reinforcing effectiveness of CRs by enhancing the predictive properties of the CR. In contrast, METH-induced increases in the reinforcing effectiveness of SRs, are mediated by the immediate sensory consequences of the light. The effects of novelty (on SRs) and METH (on both CRs and SRs) were tested. Experiment 1: rats were pre-exposed to 5 s light and water pairings presented according to a variable-time (VT) 2 min schedule or unpaired water and light presented according to independent, concurrent VT 2 min schedules. Experiment 2: rats were pre-exposed to 5 s light presented according to a VT 2 min schedule, or no stimuli. In both experiments, the pre-exposure phase was followed by a test phase in which 5 s light onset was made response-contingent on a variable-interval (VI) 2 min schedule and the effects of METH (0.5 mg/kg) were determined. Novel light onset was a more effective reinforcer than familiar light onset. METH increased the absolute rate of responding without increasing the relative frequency of responding for both CRs and SRs. Novelty plays a role in determining the reinforcing effectiveness of SRs. The results are consistent with the interpretation that METH-induced increases in reinforcer effectiveness of CRs and SRs may be mediated by immediate sensory consequences, rather than prediction. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Dopamine transporter regulates the enhancement of novelty processing by a negative emotional context.

    PubMed

    Garcia-Garcia, Manuel; Clemente, Immaculada; Domínguez-Borràs, Judith; Escera, Carles

    2010-04-01

    The dopaminergic (DA) system has been recently related the emotional modulation of cognitive processes. Moreover, patients with midbrain DA depletion, such as Parkinson's Disease (PD), have shown diminished reactivity during unpleasant events. Here, we examined the role of DA in the enhancement of novelty processing during negative emotion. Forty healthy volunteers were genotyped for the dopamine transporter (DAT) gene SLC6A3 or DAT1 and performed an auditory-visual distraction paradigm in negative and neutral emotional context conditions. 9R- individuals, associated to a lesser striatal DA display, failed to show increased distraction during negative emotion, but experienced an enhancement of the early phase of the novelty-P3 brain response, associated to the evaluation of novel events, in the negative relative to the neutral context. However, 9R+ individuals (associated to larger striatal DA display) showed larger distraction during negative emotion and larger amplitudes of the novelty-P3, irrespective of the condition. These results suggest a blunted reactivity to novelty during negative emotion in 9R- individuals due to a lesser DA display and stronger activation of the representation of novel events in the 9R+ group, due to a larger DA availability, thus reaching a ceiling effect in the neutral context condition with no further enhancement during negative emotion. The present results might help to understand the functional implications of dopamine in some neuropsychiatric disorders.

  10. Mismatch novelty exploration training enhances hippocampal synaptic plasticity: a tool for cognitive stimulation?

    PubMed

    Aidil-Carvalho, M F; Carmo, A J S; Ribeiro, J A; Cunha-Reis, D

    2017-09-08

    Memory formation relies on experience-dependent changes in synaptic strength such as long-term potentiation (LTP) or long-term depression (LTD) of synaptic activity, that in turn depend on previous learning experiences through metaplasticity. Novelty detection is a particularly important cognitive stimulus in this respect, and mismatch novelty has been associated with the activation of the hippocampal CA1 area in human studies. A single exposure a new location of known objects in a familiar environment, a behavioural mismatch novelty paradigm, is known to favour the expression of LTD in hippocampal CA3 to CA1 synaptic transmission in vivo, through short-term metaplasticity. Aiming to shape hippocampal responsiveness to synaptic plasticity phenomena we developed a training program based on exploration of a known environment containing familiar objects everyday presented in a new location. Repeated exposure to this new location of objects for two weeks caused a mild long-lasting decrease in synaptic efficacy. Furthermore, it enhanced both LTP evoked by theta-burst stimulation and depotentiation evoked by low-frequency stimulation of CA3 to CA1 hippocampal synaptic transmission in juvenile rats. This suggests that training programs using these behavioural tasks involving mismatch novelty can be used to reshape brain circuits and promote cognitive recovery in pathologies where LTP/LTD imbalance occurs, such as epilepsy, aging or Dowńs syndrome, an approach that requires further investigation at the behavioural level. Copyright © 2017. Published by Elsevier Inc.

  11. SSUnique: Detecting Sequence Novelty in Microbiome Surveys

    PubMed Central

    2016-01-01

    ABSTRACT High-throughput sequencing of small-subunit (SSU) rRNA genes has revolutionized understanding of microbial communities and facilitated investigations into ecological dynamics at unprecedented scales. Such extensive SSU rRNA gene sequence libraries, constructed from DNA extracts of environmental or host-associated samples, often contain a substantial proportion of unclassified sequences, many representing organisms with novel taxonomy (taxonomic “blind spots”) and potentially unique ecology. Indeed, these novel taxonomic lineages are associated with so-called microbial “dark matter,” which is the genomic potential of these lineages. Unfortunately, characterization beyond “unclassified” is challenging due to relatively short read lengths and large data set sizes. Here we demonstrate how mining of phylogenetically novel sequences from microbial ecosystems can be automated using SSUnique, a software pipeline that filters unclassified and/or rare operational taxonomic units (OTUs) from 16S rRNA gene sequence libraries by screening against consensus structural models for SSU rRNA. Phylogenetic position is inferred against a reference data set, and additional characterization of novel clades is also included, such as targeted probe/primer design and mining of assembled metagenomes for genomic context. We show how SSUnique reproduced a previous analysis of phylogenetic novelty from an Arctic tundra soil and demonstrate the recovery of highly novel clades from data sets associated with both the Earth Microbiome Project (EMP) and Human Microbiome Project (HMP). We anticipate that SSUnique will add to the expanding computational toolbox supporting high-throughput sequencing approaches for the study of microbial ecology and phylogeny. IMPORTANCE Extensive SSU rRNA gene sequence libraries, constructed from DNA extracts of environmental or host-associated samples, often contain many unclassified sequences, many representing organisms with novel taxonomy

  12. SSUnique: Detecting Sequence Novelty in Microbiome Surveys.

    PubMed

    Lynch, Michael D J; Neufeld, Josh D

    2016-01-01

    High-throughput sequencing of small-subunit (SSU) rRNA genes has revolutionized understanding of microbial communities and facilitated investigations into ecological dynamics at unprecedented scales. Such extensive SSU rRNA gene sequence libraries, constructed from DNA extracts of environmental or host-associated samples, often contain a substantial proportion of unclassified sequences, many representing organisms with novel taxonomy (taxonomic "blind spots") and potentially unique ecology. Indeed, these novel taxonomic lineages are associated with so-called microbial "dark matter," which is the genomic potential of these lineages. Unfortunately, characterization beyond "unclassified" is challenging due to relatively short read lengths and large data set sizes. Here we demonstrate how mining of phylogenetically novel sequences from microbial ecosystems can be automated using SSUnique, a software pipeline that filters unclassified and/or rare operational taxonomic units (OTUs) from 16S rRNA gene sequence libraries by screening against consensus structural models for SSU rRNA. Phylogenetic position is inferred against a reference data set, and additional characterization of novel clades is also included, such as targeted probe/primer design and mining of assembled metagenomes for genomic context. We show how SSUnique reproduced a previous analysis of phylogenetic novelty from an Arctic tundra soil and demonstrate the recovery of highly novel clades from data sets associated with both the Earth Microbiome Project (EMP) and Human Microbiome Project (HMP). We anticipate that SSUnique will add to the expanding computational toolbox supporting high-throughput sequencing approaches for the study of microbial ecology and phylogeny. IMPORTANCE Extensive SSU rRNA gene sequence libraries, constructed from DNA extracts of environmental or host-associated samples, often contain many unclassified sequences, many representing organisms with novel taxonomy (taxonomic "blind spots

  13. Constrained novelty search: a study on game content generation.

    PubMed

    Liapis, Antonios; Yannakakis, Georgios N; Togelius, Julian

    2015-01-01

    Novelty search is a recent algorithm geared toward exploring search spaces without regard to objectives. When the presence of constraints divides a search space into feasible space and infeasible space, interesting implications arise regarding how novelty search explores such spaces. This paper elaborates on the problem of constrained novelty search and proposes two novelty search algorithms which search within both the feasible and the infeasible space. Inspired by the FI-2pop genetic algorithm, both algorithms maintain and evolve two separate populations, one with feasible and one with infeasible individuals, while each population can use its own selection method. The proposed algorithms are applied to the problem of generating diverse but playable game levels, which is representative of the larger problem of procedural game content generation. Results show that the two-population constrained novelty search methods can create, under certain conditions, larger and more diverse sets of feasible game levels than current methods of novelty search, whether constrained or unconstrained. However, the best algorithm is contingent on the particularities of the search space and the genetic operators used. Additionally, the proposed enhancement of offspring boosting is shown to enhance performance in all cases of two-population novelty search.

  14. Novelties on Amoebiasis: A Neglected Tropical Disease

    PubMed Central

    Ximénez, Cecilia; Morán, Patricia; Rojas, Liliana; Valadez, Alicia; Gómez, Alejandro; Ramiro, Manuel; Cerritos, René; González, Enrique; Hernández, Eric; Oswaldo, Partida

    2011-01-01

    In accordance with the 1997 documents of the World Health Organization (WHO), amoebiasis is defined as the infection by the protozoan parasite Entamoeba histolytica with or without clinical manifestations. The only known natural host of E. histolytica is the human with the large intestine as major target organ. This parasite has a very simple life cycle in which the infective form is the cyst, considered a resistant form of parasite: The asymptomatic cyst passers and the intestinal amoebiasis patients are the transmitters; they excrete cysts in their feces, which can contaminate food and water sources. E. histolytica sensu stricto is the potentially pathogenic species and E. dispar is a commensal non-pathogenic Entamoeba. Both species are biochemical, immunological and genetically distinct. The knowledge of both species with different pathogenic phenotypes comes from a large scientific debate during the second half of the 20th century, which gave place to the rapid development of diagnostics technology based on molecular and immunological strategies. During the last ten years, knowledge of the new epidemiology of amoebiasis in different geographic endemic and non-endemic areas has been obtained by applying mostly molecular techniques. In the present work we highlight novelties on human infection and the disease that can help the general physician from both endemic and non-endemic countries in their medical practice, particularly, now that emigration is undoubtedly a global phenomenon that is modifying the previous geography of infectious diseases worldwide. PMID:21731305

  15. Novelties on amoebiasis: a neglected tropical disease.

    PubMed

    Ximénez, Cecilia; Morán, Patricia; Rojas, Liliana; Valadez, Alicia; Gómez, Alejandro; Ramiro, Manuel; Cerritos, René; González, Enrique; Hernández, Eric; Oswaldo, Partida

    2011-04-01

    In accordance with the 1997 documents of the World Health Organization (WHO), amoebiasis is defined as the infection by the protozoan parasite Entamoeba histolytica with or without clinical manifestations. The only known natural host of E. histolytica is the human with the large intestine as major target organ. This parasite has a very simple life cycle in which the infective form is the cyst, considered a resistant form of parasite: The asymptomatic cyst passers and the intestinal amoebiasis patients are the transmitters; they excrete cysts in their feces, which can contaminate food and water sources. E. histolytica sensu stricto is the potentially pathogenic species and E. dispar is a commensal non-pathogenic Entamoeba. Both species are biochemical, immunological and genetically distinct. The knowledge of both species with different pathogenic phenotypes comes from a large scientific debate during the second half of the 20(th) century, which gave place to the rapid development of diagnostics technology based on molecular and immunological strategies. During the last ten years, knowledge of the new epidemiology of amoebiasis in different geographic endemic and non-endemic areas has been obtained by applying mostly molecular techniques. In the present work we highlight novelties on human infection and the disease that can help the general physician from both endemic and non-endemic countries in their medical practice, particularly, now that emigration is undoubtedly a global phenomenon that is modifying the previous geography of infectious diseases worldwide.

  16. The availability of novelty sweets within high school localities.

    PubMed

    Aljawad, A; Morgan, M Z; Rees, J S; Fairchild, R

    2016-06-10

    Background Reducing sugar consumption is a primary focus of current global public health policy. Achieving 5% of total energy from free sugars will be difficult acknowledging the concentration of free sugars in sugar sweetened beverages, confectionery and as hidden sugars in many savoury items. The expansion of the novelty sweet market in the UK has significant implications for children and young adults as they contribute to dental caries, dental erosion and obesity.Objective To identify the most available types of novelty sweets within the high school fringe in Cardiff, UK and to assess their price range and where and how they were displayed in shops.Subjects and methods Shops within a ten minute walking distance around five purposively selected high schools in the Cardiff aea representing different levels of deprivation were visited. Shops in Cardiff city centre and three supermarkets were also visited to identify the most commonly available novelty sweets.Results The ten most popular novelty sweets identified in these scoping visits were (in descending order): Brain Licker, Push Pop, Juicy Drop, Lickedy Lips, Big Baby Pop, Vimto candy spray, Toxic Waste, Tango candy spray, Brain Blasterz Bitz and Mega Mouth candy spray. Novelty sweets were located on low shelves which were accessible to all age-groups in 73% (14 out of 19) of the shops. Novelty sweets were displayed in the checkout area in 37% (seven out of 19) shops. The price of the top ten novelty sweets ranged from 39p to £1.Conclusion A wide range of acidic and sugary novelty sweets were easily accessible and priced within pocket money range. Those personnel involved in delivering dental and wider health education or health promotion need to be aware of recent developments in children's confectionery. The potential effects of these novelty sweets on both general and dental health require further investigation.

  17. Neuronal control of locomotor handedness in Drosophila

    PubMed Central

    Buchanan, Sean M.; Kain, Jamey S.; de Bivort, Benjamin L.

    2015-01-01

    Genetically identical individuals display variability in their physiology, morphology, and behaviors, even when reared in essentially identical environments, but there is little mechanistic understanding of the basis of such variation. Here, we investigated whether Drosophila melanogaster displays individual-to-individual variation in locomotor behaviors. We developed a new high-throughout platform capable of measuring the exploratory behavior of hundreds of individual flies simultaneously. With this approach, we find that, during exploratory walking, individual flies exhibit significant bias in their left vs. right locomotor choices, with some flies being strongly left biased or right biased. This idiosyncrasy was present in all genotypes examined, including wild-derived populations and inbred isogenic laboratory strains. The biases of individual flies persist for their lifetime and are nonheritable: i.e., mating two left-biased individuals does not yield left-biased progeny. This locomotor handedness is uncorrelated with other asymmetries, such as the handedness of gut twisting, leg-length asymmetry, and wing-folding preference. Using transgenics and mutants, we find that the magnitude of locomotor handedness is under the control of columnar neurons within the central complex, a brain region implicated in motor planning and execution. When these neurons are silenced, exploratory laterality increases, with more extreme leftiness and rightiness. This observation intriguingly implies that the brain may be able to dynamically regulate behavioral individuality. PMID:25953337

  18. Locomotor Experience Affects Self and Emotion

    ERIC Educational Resources Information Center

    Uchiyama, Ichiro; Anderson, David I.; Campos, Joseph J.; Witherington, David; Frankel, Carl B.; Lejeune, Laure; Barbu-Roth, Marianne

    2008-01-01

    Two studies investigated the role of locomotor experience on visual proprioception in 8-month-old infants. "Visual proprioception" refers to the sense of self-motion induced in a static person by patterns of optic flow. A moving room apparatus permitted displacement of an entire enclosure (except for the floor) or the side walls and…

  19. Locomotor Experience Affects Self and Emotion

    ERIC Educational Resources Information Center

    Uchiyama, Ichiro; Anderson, David I.; Campos, Joseph J.; Witherington, David; Frankel, Carl B.; Lejeune, Laure; Barbu-Roth, Marianne

    2008-01-01

    Two studies investigated the role of locomotor experience on visual proprioception in 8-month-old infants. "Visual proprioception" refers to the sense of self-motion induced in a static person by patterns of optic flow. A moving room apparatus permitted displacement of an entire enclosure (except for the floor) or the side walls and…

  20. Neuronal control of locomotor handedness in Drosophila.

    PubMed

    Buchanan, Sean M; Kain, Jamey S; de Bivort, Benjamin L

    2015-05-26

    Genetically identical individuals display variability in their physiology, morphology, and behaviors, even when reared in essentially identical environments, but there is little mechanistic understanding of the basis of such variation. Here, we investigated whether Drosophila melanogaster displays individual-to-individual variation in locomotor behaviors. We developed a new high-throughout platform capable of measuring the exploratory behavior of hundreds of individual flies simultaneously. With this approach, we find that, during exploratory walking, individual flies exhibit significant bias in their left vs. right locomotor choices, with some flies being strongly left biased or right biased. This idiosyncrasy was present in all genotypes examined, including wild-derived populations and inbred isogenic laboratory strains. The biases of individual flies persist for their lifetime and are nonheritable: i.e., mating two left-biased individuals does not yield left-biased progeny. This locomotor handedness is uncorrelated with other asymmetries, such as the handedness of gut twisting, leg-length asymmetry, and wing-folding preference. Using transgenics and mutants, we find that the magnitude of locomotor handedness is under the control of columnar neurons within the central complex, a brain region implicated in motor planning and execution. When these neurons are silenced, exploratory laterality increases, with more extreme leftiness and rightiness. This observation intriguingly implies that the brain may be able to dynamically regulate behavioral individuality.

  1. Dissociation of corticotropin-releasing factor receptor subtype involvement in sensitivity to locomotor effects of methamphetamine and cocaine

    PubMed Central

    Giardino, William J.; Mark, Gregory P.; Stenzel-Poore, Mary P.

    2011-01-01

    Rationale Enhanced sensitivity to the euphoric and locomotor-activating effects of psychostimulants may influence an individual's predisposition to drug abuse and addiction. While drug-induced behaviors are mediated by the actions of several neurotransmitter systems, past research revealed that the corticotropin-releasing factor (CRF) system is important in driving the acute locomotor response to psychostimulants. Objectives We previously reported that genetic deletion of the CRF type-2 receptor (CRF-R2), but not the CRF type-1 receptor (CRF-R1) dampened the acute locomotor stimulant response to methamphetamine (1 mg/kg). These results contrasted with previous studies implicating CRF-R1 in the locomotor effects of psychostimulants. Since the majority of previous studies focused on cocaine, rather than methamphetamine, we set out to test the hypothesis that these drugs differentially engage CRF-R1 and CRF-R2. Methods We expanded our earlier findings by first replicating our previous experiments at a higher dose of methamphetamine (2 mg/kg), and by assessing the effects of the CRF-R1-selective antagonist CP-376,395 (10 mg/kg) on methamphetamine-induced locomotor activity. Next, we used both genetic and pharmacological tools to examine the specific components of the CRF system underlying the acute locomotor response to cocaine (5–10 mg/kg). Results While genetic deletion of CRF-R2 dampened the locomotor response to methamphetamine (but not cocaine), genetic deletion and pharmacological blockade of CRF-R1 dampened the locomotor response to cocaine (but not methamphetamine). Conclusions These findings highlight the differential involvement of CRF receptors in acute sensitivity to two different stimulant drugs of abuse, providing an intriguing basis for the development of more targeted therapeutics for psychostimulant addiction. PMID:21833501

  2. Novelty, Stress, and Biological Roots in Human Market Behavior

    PubMed Central

    Sarapultsev, Alexey; Sarapultsev, Petr

    2014-01-01

    Although studies examining the biological roots of human behavior have been conducted since the seminal work Kahneman and Tversky, crises and panics have not disappeared. The frequent occurrence of various types of crises has led some economists to the conviction that financial markets occasionally praise irrational judgments and that market crashes cannot be avoided a priori (Sornette 2009; Smith 2004). From a biological point of view, human behaviors are essentially the same during crises accompanied by stock market crashes and during bubble growth when share prices exceed historic highs. During those periods, most market participants see something new for themselves, and this inevitably induces a stress response in them with accompanying changes in their endocrine profiles and motivations. The result is quantitative and qualitative changes in behavior (Zhukov 2007). An underestimation of the role of novelty as a stressor is the primary shortcoming of current approaches for market research. When developing a mathematical market model, it is necessary to account for the biologically determined diphasisms of human behavior in everyday low-stress conditions and in response to stressors. This is the only type of approach that will enable forecasts of market dynamics and investor behaviors under normal conditions as well as during bubbles and panics. PMID:25379268

  3. Novelty, stress, and biological roots in human market behavior.

    PubMed

    Sarapultsev, Alexey; Sarapultsev, Petr

    2014-03-01

    Although studies examining the biological roots of human behavior have been conducted since the seminal work Kahneman and Tversky, crises and panics have not disappeared. The frequent occurrence of various types of crises has led some economists to the conviction that financial markets occasionally praise irrational judgments and that market crashes cannot be avoided a priori (Sornette 2009; Smith 2004). From a biological point of view, human behaviors are essentially the same during crises accompanied by stock market crashes and during bubble growth when share prices exceed historic highs. During those periods, most market participants see something new for themselves, and this inevitably induces a stress response in them with accompanying changes in their endocrine profiles and motivations. The result is quantitative and qualitative changes in behavior (Zhukov 2007). An underestimation of the role of novelty as a stressor is the primary shortcoming of current approaches for market research. When developing a mathematical market model, it is necessary to account for the biologically determined diphasisms of human behavior in everyday low-stress conditions and in response to stressors. This is the only type of approach that will enable forecasts of market dynamics and investor behaviors under normal conditions as well as during bubbles and panics.

  4. Striatal Activity Underlies Novelty-Based Choice in Humans

    PubMed Central

    Wittmann, Bianca C.; Daw, Nathaniel D.; Seymour, Ben; Dolan, Raymond J.

    2008-01-01

    Summary The desire to seek new and unfamiliar experiences is a fundamental behavioral tendency in humans and other species. In economic decision making, novelty seeking is often rational, insofar as uncertain options may prove valuable and advantageous in the long run. Here, we show that, even when the degree of perceptual familiarity of an option is unrelated to choice outcome, novelty nevertheless drives choice behavior. Using functional magnetic resonance imaging (fMRI), we show that this behavior is specifically associated with striatal activity, in a manner consistent with computational accounts of decision making under uncertainty. Furthermore, this activity predicts interindividual differences in susceptibility to novelty. These data indicate that the brain uses perceptual novelty to approximate choice uncertainty in decision making, which in certain contexts gives rise to a newly identified and quantifiable source of human irrationality. PMID:18579085

  5. Locomotor Muscle Fatigue Does Not Alter Oxygen Uptake Kinetics during High-Intensity Exercise

    PubMed Central

    Hopker, James G.; Caporaso, Giuseppe; Azzalin, Andrea; Carpenter, Roger; Marcora, Samuele M.

    2016-01-01

    The V˙O2 slow component (V˙O2sc) that develops during high-intensity aerobic exercise is thought to be strongly associated with locomotor muscle fatigue. We sought to experimentally test this hypothesis by pre-fatiguing the locomotor muscles used during subsequent high-intensity cycling exercise. Over two separate visits, eight healthy male participants were asked to either perform a non-metabolically stressful 100 intermittent drop-jumps protocol (pre-fatigue condition) or rest for 33 min (control condition) according to a random and counterbalanced order. Locomotor muscle fatigue was quantified with 6-s maximal sprints at a fixed pedaling cadence of 90 rev·min−1. Oxygen kinetics and other responses (heart rate, capillary blood lactate concentration and rating of perceived exertion, RPE) were measured during two subsequent bouts of 6 min cycling exercise at 50% of the delta between the lactate threshold and V˙O2max determined during a preliminary incremental exercise test. All tests were performed on the same cycle ergometer. Despite significant locomotor muscle fatigue (P = 0.03), the V˙O2sc was not significantly different between the pre-fatigue (464 ± 301 mL·min−1) and the control (556 ± 223 mL·min−1) condition (P = 0.50). Blood lactate response was not significantly different between conditions (P = 0.48) but RPE was significantly higher following the pre-fatiguing exercise protocol compared with the control condition (P < 0.01) suggesting higher muscle recruitment. These results demonstrate experimentally that locomotor muscle fatigue does not significantly alter the V˙O2 kinetic response to high intensity aerobic exercise, and challenge the hypothesis that the V˙O2sc is strongly associated with locomotor muscle fatigue. PMID:27790156

  6. Novelty, conditioning and attentional bias to sexual rewards.

    PubMed

    Banca, Paula; Morris, Laurel S; Mitchell, Simon; Harrison, Neil A; Potenza, Marc N; Voon, Valerie

    2016-01-01

    The Internet provides a large source of novel and rewarding stimuli, particularly with respect to sexually explicit materials. Novelty-seeking and cue-conditioning are fundamental processes underlying preference and approach behaviors implicated in disorders of addiction. Here we examine these processes in individuals with compulsive sexual behaviors (CSB), hypothesizing a greater preference for sexual novelty and stimuli conditioned to sexual rewards relative to healthy volunteers. Twenty-two CSB males and forty age-matched male volunteers were tested in two separate behavioral tasks focusing on preferences for novelty and conditioned stimuli. Twenty subjects from each group were also assessed in a third conditioning and extinction task using functional magnetic resonance imaging. CSB was associated with enhanced novelty preference for sexual, as compared to control images, and a generalized preference for cues conditioned to sexual and monetary versus neutral outcomes compared to healthy volunteers. CSB individuals also had greater dorsal cingulate habituation to repeated sexual versus monetary images with the degree of habituation correlating with enhanced preference for sexual novelty. Approach behaviors to sexually conditioned cues dissociable from novelty preference were associated with an early attentional bias to sexual images. This study shows that CSB individuals have a dysfunctional enhanced preference for sexual novelty possibly mediated by greater cingulate habituation along with a generalized enhancement of conditioning to rewards. We further emphasize a dissociable role for cue-conditioning and novelty preference on the early attentional bias for sexual cues. These findings have wider relevance as the Internet provides a broad range of novel and potentially rewarding stimuli. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Novelty, conditioning and attentional bias to sexual rewards

    PubMed Central

    Banca, Paula; Morris, Laurel S.; Mitchell, Simon; Harrison, Neil A.; Potenza, Marc N.; Voon, Valerie

    2016-01-01

    The Internet provides a large source of novel and rewarding stimuli, particularly with respect to sexually explicit materials. Novelty-seeking and cue-conditioning are fundamental processes underlying preference and approach behaviors implicated in disorders of addiction. Here we examine these processes in individuals with compulsive sexual behaviors (CSB), hypothesizing a greater preference for sexual novelty and stimuli conditioned to sexual rewards relative to healthy volunteers. Twenty-two CSB males and forty age-matched male volunteers were tested in two separate behavioral tasks focusing on preferences for novelty and conditioned stimuli. Twenty subjects from each group were also assessed in a third conditioning and extinction task using functional magnetic resonance imaging. CSB was associated with enhanced novelty preference for sexual, as compared to control images, and a generalized preference for cues conditioned to sexual and monetary versus neutral outcomes compared to healthy volunteers. CSB individuals also had greater dorsal cingulate habituation to repeated sexual versus monetary images with the degree of habituation correlating with enhanced preference for sexual novelty. Approach behaviors to sexually conditioned cues dissociable from novelty preference were associated with an early attentional bias to sexual images. This study shows that CSB individuals have a dysfunctional enhanced preference for sexual novelty possibly mediated by greater cingulate habituation along with a generalized enhancement of conditioning to rewards. We further emphasize a dissociable role for cue-conditioning and novelty preference on the early attentional bias for sexual cues. These findings have wider relevance as the Internet provides a broad range of novel and potentially rewarding stimuli. PMID:26606725

  8. Monitoring Locomotor Load in Soccer: Is Metabolic Power, Powerful?

    PubMed

    Buchheit, M; Manouvrier, C; Cassirame, J; Morin, J-B

    2015-12-01

    The aim of the present study was to examine the validity and reliability of metabolic power (P) estimated from locomotor demands during soccer-specific drills. 14 highly-trained soccer players performed a soccer-specific circuit with the ball (3×1-min bouts, interspersed with 30-s passive recovery) on 2 different occasions. Locomotor activity was monitored with 4-Hz GPSs, while oxygen update (VO2) was collected with a portable gas analyzer. P was calculated using either net VO2 responses and traditional calorimetry principles (PVO2, W.kg(-1)) or locomotor demands (PGPS, W.kg(-1)). Distance covered into different speed, acceleration and P zones was recorded. While PGPS was 29±10% lower than PVO2 (d<- 3) during the exercise bouts, it was 85±7% lower (d<- 8) during recovery phases. The typical error between PGPS vs. PVO2 was moderate: 19.8%, 90% confidence limits: (18.4;21.6). The correlation between both estimates of P was small: 0.24 (0.14;0.33). Very large day-to-day variations were observed for acceleration, deceleration and > 20 W.kg(-1) distances (all CVs > 50%), while average Po2 and PGPS showed CVs < 10%. ICC ranged from very low- (acceleration and > 20 W.kg(-1) distances) to-very high (PVO2). PGPS largely underestimates the energy demands of soccer-specific drills, especially during the recovery phases. The poor reliability of PGPS >20 W.kg(-1) questions its value for monitoring purposes in soccer.

  9. Locomotor skills and balance strategies in adolescents idiopathic scoliosis.

    PubMed

    Mallau, Sophie; Bollini, Gérard; Jouve, Jean-Luc; Assaiante, Christine

    2007-01-01

    Locomotor balance control assessment was performed to study the effect of idiopathic scoliosis on head-trunk coordination in 17 patients with adolescent idiopathic scoliosis (AIS) and 16 control subjects. The aim of this study was to explore the functional effects of structural spinal deformations like idiopathic scoliosis on the balance strategies used during locomotion. Up to now, the repercussion of the idiopathic scoliosis on head-trunk coordination and balance strategies during locomotion is relatively unknown. Seventeen patients with AIS (mean age 14 years 3 months, 10 degrees < Cobb angle > 30 degrees) and 16 control subjects (mean age 14 years 1 month) were tested during various locomotor tasks: walking on the ground, walking on a line, and walking on a beam. Balance control was examined in terms of rotation about the vertical axis (yaw) and on a frontal plane (roll). Kinematics of foot, pelvis, trunk, shoulder, and head rotations were measured with an automatic optical TV image processor in order to calculate angular dispersions and segmental stabilizations. Decreasing the walking speed is the main adaptive strategy used in response to balance problems in control subjects as well as patients with AIS. However, patients with AIS performed walking tasks more slowly than normal subjects (around 15%). Moreover, the pelvic stabilization is preserved, despite the structural changes affecting the spine. Lastly, the biomechanical defect resulting from idiopathic scoliosis mainly affects the yaw head stabilization during locomotion. Patients with AIS show substantial similarities with control subjects in adaptive strategies relative to locomotor velocity as well as balance control based on segmental stabilization. In contrast, the loss of the yaw head stabilization strategies, mainly based on the use of vestibular information, probably reflects the presence of vestibular deficits in the patients with AIS.

  10. Development of a Countermeasure to Mitigate Postflight Locomotor Dysfunction

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Warren, L. E.; Ruttley, T. M.

    2006-01-01

    Astronauts returning from space flight experience locomotor dysfunction following their return to Earth. Our laboratory is currently developing a gait adaptability training program that is designed to facilitate recovery of locomotor function following a return to a gravitational environment. The training program exploits the ability of the sensorimotor system to generalize from exposure to multiple adaptive challenges during training so that the gait control system essentially learns to learn and therefore can reorganize more rapidly when faced with a novel adaptive challenge. Evidence for the potential efficacy of an adaptive generalization gait training program can be obtained from numerous studies in the motor learning literature which have demonstrated that systematically varying the conditions of training enhances the ability of the performer to learn and retain a novel motor task. These variable practice training approaches have been used in applied contexts to improve motor skills required in a number of different sports. The central nervous system (CNS) can produce voluntary movement in an almost infinite number of ways. For example, locomotion can be achieved with many different combinations of joint angles, muscle activation patterns and forces. The CNS can exploit these degrees of freedom to enhance motor response adaptability during periods of adaptive flux like that encountered during a change in gravitational environment. Ultimately, the functional goal of an adaptive generalization countermeasure is not necessarily to immediately return movement patterns back to normal. Rather the training regimen should facilitate the reorganization of available sensory and motor subsystems to achieve safe and effective locomotion as soon as possible after long duration space flight. Indeed, this approach has been proposed as a basic feature underlying effective neurological rehabilitation. We have previously confirmed that subjects participating in an adaptive

  11. Development of a Countermeasure to Mitigate Postflight Locomotor Dysfunction

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Warren, L. E.; Ruttley, T. M.

    2006-01-01

    Astronauts returning from space flight experience locomotor dysfunction following their return to Earth. Our laboratory is currently developing a gait adaptability training program that is designed to facilitate recovery of locomotor function following a return to a gravitational environment. The training program exploits the ability of the sensorimotor system to generalize from exposure to multiple adaptive challenges during training so that the gait control system essentially learns to learn and therefore can reorganize more rapidly when faced with a novel adaptive challenge. Evidence for the potential efficacy of an adaptive generalization gait training program can be obtained from numerous studies in the motor learning literature which have demonstrated that systematically varying the conditions of training enhances the ability of the performer to learn and retain a novel motor task. These variable practice training approaches have been used in applied contexts to improve motor skills required in a number of different sports. The central nervous system (CNS) can produce voluntary movement in an almost infinite number of ways. For example, locomotion can be achieved with many different combinations of joint angles, muscle activation patterns and forces. The CNS can exploit these degrees of freedom to enhance motor response adaptability during periods of adaptive flux like that encountered during a change in gravitational environment. Ultimately, the functional goal of an adaptive generalization countermeasure is not necessarily to immediately return movement patterns back to normal. Rather the training regimen should facilitate the reorganization of available sensory and motor subsystems to achieve safe and effective locomotion as soon as possible after long duration space flight. Indeed, this approach has been proposed as a basic feature underlying effective neurological rehabilitation. We have previously confirmed that subjects participating in an adaptive

  12. Enhancing offspring hypothalamic-pituitary-adrenal (HPA) regulation via systematic novelty exposure: the influence of maternal HPA function.

    PubMed

    Dinces, Sarah M; Romeo, Russell D; McEwen, Bruce S; Tang, Akaysha C

    2014-01-01

    In the rat, repeated brief exposures to novelty early in life can induce long-lasting enhancements in adult cognitive, social, emotional, and neuroendocrine function. Family-to-family variations in these intervention effects on adult offspring are predicted by the mother's ability to mount a rapid corticosterone (CORT) response to the onset of an acute stressor. Here, in Long-Evans rats, we investigated whether neonatal and adulthood novelty exposure, each individually and in combination, can enhance offspring hypothalamic-pituitary-adrenal (HPA) regulation. Using a 2 × 2 within-litter design, one half of each litter were exposed to a relatively novel non-home environment for 3-min (Neo_Novel) daily during infancy (PND 1-21) and the other half of the litter remained in the home cage (Neo_Home); we further exposed half of these two groups to early adulthood (PND 54-63) novelty exposure in an open field and the remaining siblings stayed in their home cages. Two aspects of HPA regulation were assessed: the ability to maintain a low level of resting CORT (CORTB) and the ability to mount a large rapid CORT response (CORTE) to the onset of an acute stressor. Assessment of adult offspring's ability to regulate HPA regulation began at 370 days of age. We further investigated whether the novelty exposure effects on offspring HPA regulation are sensitive to the context of maternal HPA regulation by assessing maternal HPA regulation similarly beginning 7 days after her pups were weaned. We found that at the population level, rats receiving neonatal, but not early adulthood exposure or both, showed a greater rapid CORTE than their home-staying siblings. At the individual family level, these novelty effects are positively associated with maternal CORTE. These results suggest that early experience of novelty can enhance the offspring's ability to mount a rapid response to environmental challenge and the success of such early life intervention is critically dependent upon the

  13. Multilevel Cortical Processing of Somatosensory Novelty: A Magnetoencephalography Study

    PubMed Central

    Naeije, Gilles; Vaulet, Thibaut; Wens, Vincent; Marty, Brice; Goldman, Serge; De Tiège, Xavier

    2016-01-01

    Using magnetoencephalography (MEG), this study investigates the spatio-temporal dynamics of the multilevel cortical processing of somatosensory change detection. Neuromagnetic signals of 16 healthy adult subjects (7 females and 9 males, mean age 29 ± 3 years) were recorded using whole-scalp-covering MEG while they underwent an oddball paradigm based on simple standard (right index fingertip tactile stimulation) and deviant (simultaneous right index fingertip and middle phalanx tactile stimulation) stimuli gathered into sequences to create and then deviate from stimulus patterns at multiple (local vs. global) levels of complexity. Five healthy adult subjects (3 females and 2 males, mean age 31, 6 ± 2 years) also underwent a similar oddball paradigm in which standard and deviant stimuli were flipped. Local deviations led to a somatosensory mismatch response peaking at 55–130 ms post-stimulus onset with a cortical generator located at the contralateral secondary somatosensory (cSII) cortex. The mismatch response was independent of the deviant stimuli physical characteristics. Global deviants led to a P300 response with cortical sources located bilaterally at temporo-parietal junction (TPJ) and supplementary motor area (SMA). The posterior parietal cortex (PPC) and the SMA were found to generate a contingent magnetic variation (CMV) attributed to top-down expectations. Amplitude of mismatch responses were modulated by top-down expectations and correlated with both the magnitude of the CMV and the P300 amplitude at the right TPJ. These results provide novel empirical evidence for a unified sensory novelty detection system in the human brain by linking detection of salient sensory stimuli in personal and extra-personal spaces to a common framework of multilevel cortical processing. PMID:27313523

  14. Novelty P3 reductions in depression: Characterization using principal components analysis (PCA) of current source density (CSD) waveforms

    PubMed Central

    TENKE, CRAIG E.; KAYSER, JÜRGEN; STEWART, JONATHAN W.; BRUDER, GERARD E.

    2012-01-01

    We previously reported a novelty P3 reduction in depressed patients compared to healthy controls (n = 20 per group) in a novelty oddball task using a 31-channel montage. In an independent replication and extension using a 67-channel montage (n = 49 per group), reference-free current source density (CSD) waveforms were simplified and quantified by a temporal, covariance-based principal components analysis (PCA) (unrestricted Varimax rotation), yielding factor solutions consistent with other oddball tasks. A factor with a loadings peak at 343 ms summarized the target P3b source as well as a secondary midline frontocentral source for novels and targets. An earlier novelty vertex source (NVS) at 241 ms was present for novels, but not targets, and was reduced in patients. Compatible CSD-PCA findings were also confirmed for the original low-density sample. Results are consistent with a reduced novelty response in clinical depression, involving the early phase of the frontocentral novelty P3. PMID:19761526

  15. Withdrawal from repeated treatment with amphetamine reduces novelty-seeking behavior and enhances environmental habituation in mice.

    PubMed

    Fukushiro, Daniela F; Mári-Kawamoto, Elisa; Aramini, Tatiana C F; Saito, Luis P; Costa, Jacqueline M; Josino, Fabiana S; Frussa-Filho, Roberto

    2011-11-01

    Anhedonia associated with a dysphoric state is an important feature of amphetamine withdrawal in humans. We aimed to investigate the effects of amphetamine withdrawal on two motivation-related behaviors in mice: novelty seeking and environmental habituation. Because anxiety can interfere with the behavioral outcome of other tasks, amphetamine-withdrawn mice were also evaluated in the elevated plus maze. Swiss male mice (three months old) were treated with 2.0mg/kg amphetamine for 13 days, every other day, in their home cages (a total of seven injections). Twenty-four hours after withdrawal from drug treatment, mice were tested in a free-choice novelty apparatus containing one familiar and one novel compartment or in the elevated plus maze. Novelty-seeking behavior was assessed by comparing the time spent in the novel compartment vs. the familiar compartment, whereas environmental habituation was concomitantly evaluated by the time-response curve of total locomotion (novel+familiar). Novelty seeking was decreased during amphetamine withdrawal, and this result was not associated with changes in the anxiety-like behavior of mice. Additionally, amphetamine withdrawal enhanced environmental habituation. The concomitant decrease in novelty seeking and the increase in environmental habituation seem to be related to amphetamine withdrawal-induced anhedonia. Thus, the model proposed here could be used as a tool for the study of mechanisms and potential treatment of the anhedonic behavioral consequences of psychostimulant withdrawal.

  16. Balancing novelty with confined chemical space in modern drug discovery.

    PubMed

    Medina-Franco, José L; Martinez-Mayorga, Karina; Meurice, Nathalie

    2014-02-01

    The concept of chemical space has broad applications in drug discovery. In response to the needs of drug discovery campaigns, different approaches are followed to efficiently populate, mine and select relevant chemical spaces that overlap with biologically relevant chemical spaces. This paper reviews major trends in current drug discovery and their impact on the mining and population of chemical space. We also survey different approaches to develop screening libraries with confined chemical spaces balancing physicochemical properties. In this context, the confinement is guided by criteria that can be divided in two broad categories: i) library design focused on a relevant therapeutic target or disease and ii) library design focused on the chemistry or a desired molecular function. The design and development of chemical libraries should be associated with the specific purpose of the library and the project goals. The high complexity of drug discovery and the inherent imperfection of individual experimental and computational technologies prompt the integration of complementary library design and screening approaches to expedite the identification of new and better drugs. Library design approaches including diversity-oriented synthesis, biological-oriented synthesis or combinatorial library design, to name a few, and the design of focused libraries driven by target/disease, chemical structure or molecular function are more efficient if they are guided by multi-parameter optimization. In this context, consideration of pharmaceutically relevant properties is essential for balancing novelty with chemical space in drug discovery.

  17. Novelty and Inductive Generalization in Human Reinforcement Learning

    PubMed Central

    Gershman, Samuel J.; Niv, Yael

    2015-01-01

    In reinforcement learning, a decision maker searching for the most rewarding option is often faced with the question: what is the value of an option that has never been tried before? One way to frame this question is as an inductive problem: how can I generalize my previous experience with one set of options to a novel option? We show how hierarchical Bayesian inference can be used to solve this problem, and describe an equivalence between the Bayesian model and temporal difference learning algorithms that have been proposed as models of reinforcement learning in humans and animals. According to our view, the search for the best option is guided by abstract knowledge about the relationships between different options in an environment, resulting in greater search efficiency compared to traditional reinforcement learning algorithms previously applied to human cognition. In two behavioral experiments, we test several predictions of our model, providing evidence that humans learn and exploit structured inductive knowledge to make predictions about novel options. In light of this model, we suggest a new interpretation of dopaminergic responses to novelty. PMID:25808176

  18. Novelty and Inductive Generalization in Human Reinforcement Learning.

    PubMed

    Gershman, Samuel J; Niv, Yael

    2015-07-01

    In reinforcement learning (RL), a decision maker searching for the most rewarding option is often faced with the question: What is the value of an option that has never been tried before? One way to frame this question is as an inductive problem: How can I generalize my previous experience with one set of options to a novel option? We show how hierarchical Bayesian inference can be used to solve this problem, and we describe an equivalence between the Bayesian model and temporal difference learning algorithms that have been proposed as models of RL in humans and animals. According to our view, the search for the best option is guided by abstract knowledge about the relationships between different options in an environment, resulting in greater search efficiency compared to traditional RL algorithms previously applied to human cognition. In two behavioral experiments, we test several predictions of our model, providing evidence that humans learn and exploit structured inductive knowledge to make predictions about novel options. In light of this model, we suggest a new interpretation of dopaminergic responses to novelty. Copyright © 2015 Cognitive Science Society, Inc.

  19. Novelty-seeking and avoidant coping strategies are associated with academic stress in Korean medical students.

    PubMed

    An, Hoyoung; Chung, Seockhoon; Park, Jangho; Kim, Seong-Yoon; Kim, Kyung Mo; Kim, Ki-Soo

    2012-12-30

    High levels of stress and depression in medical students is raising concern. In this study, we sought to identify coping strategies and other factors influencing academic stress in medical students. We enrolled 157 students from the University of Ulsan College of Medicine, Korea, in November, 2010. We used the Medical Stress Scale, Temperament and Character Inventory, Hamilton Depression Scale, Beck Depression Inventory, and Coping Response Inventory to assess psychological parameters. We used Pearson's correlation and linear regression analyses to analyze the data. Novelty-seeking, self-directedness, cooperativeness, coping strategy, and depression scale scores all correlated significantly with stress level. Linear regression analysis indicated that students who are novelty-seeking, likely to use avoidant coping strategies, and unlikely to use active-cognitive and active-behavioral strategies tend to have higher stress levels. Reduction of stress in medical students may be achieved through evaluation of coping strategies and personality features and use of interventions to promote active coping strategies.

  20. Dissociating hippocampal and basal ganglia contributions to category learning using stimulus novelty and subjective judgments

    PubMed Central

    Seger, Carol A.; Dennison, Christina S.; Lopez-Paniagua, Dan; Peterson, Erik J.; Roark, Aubrey A.

    2011-01-01

    We identified factors leading to hippocampal and basal ganglia recruitment during categorization learning. Subjects alternated between blocks of a standard trial and error category learning task and a subjective judgment task. In the subjective judgments task subjects categorized the stimulus and then instead of receiving feedback they indicated the basis of their response using 4 options: Remember: Conscious episodic memory of previous trials. Know-Automatic: Automatic, rapid response accompanied by conscious awareness of category membership. Know-Intuition: A “gut feeling” without fully conscious knowledge of category membership. Guess: Guessing. In addition, new stimuli were introduced throughout the experiment to examine effects of novelty. Categorization overall recruited both the basal ganglia and posterior hippocampus. However, basal ganglia activity was found during Know judgments (both Automatic and Intuition), whereas posterior hippocampus activity was found during Remember judgments. Granger causality mapping indicated interactions between the basal ganglia and hippocampus, with the putamen exerting directed influence on the posterior hippocampus, which in turn exerted directed influence on the posterior caudate nucleus. We also found a region of anterior hippocampus that showed decreased activity relative to baseline during categorization overall, and showed a strong novelty effect. Our results indicate that subjective measures may be effective in dissociating basal ganglia from hippocampal dependent learning, and that the basal ganglia are involved in both conscious and unconscious learning. They also indicate a dissociation within the hippocampus, in which the anterior regions are sensitive to novelty, and the posterior regions are involved in memory based categorization learning. PMID:21255655

  1. Damage location in an isotropic plate using a vector of novelty indices

    NASA Astrophysics Data System (ADS)

    Mustapha, F.; Manson, G.; Worden, K.; Pierce, S. G.

    2007-05-01

    This paper presents a novel approach to detecting and localising structural defects based on a novelty detection method, outlier analysis (OA), and a multi-layer perceptron (MLP) neural network. In order to assess the effectiveness of the approach, a thin rectangular plate with isotropic behaviour was evaluated experimentally. The scope of this present work also comprises an investigation of the scattering effect of an ultrasonic guided wave on the tested plate under both damaged and undamaged conditions. The wave propagation is sequentially transmitted and captured by 8 PZT patches bonded on the plate, forming a sensor network on the tested isotropic rectangular structure. An in-house 8 channel multiplexer is incorporated in this small scale and low-cost 'structural health monitoring' (SHM) system to effectively swap the PZTs role from sensor to actuator and vice-versa. The 'real-time damage demonstrator' software is primarily developed to acquire and store the waveform responses. These sets of scattering waveform responses representing normal and damage conditions are transformed into a set of novelty indices that ultimately determine the true conditions of the tested structure. The acquired novelty indices representing the available sensor paths are used as the inputs for the neural network incorporating the MLP architecture to compute and predict the damage location in the x and y location on the tested isotopic plate.

  2. Visual novel stimuli in an ERP novelty oddball paradigm: effects of familiarity on repetition and recognition memory.

    PubMed

    Cycowicz, Yael M; Friedman, David

    2007-01-01

    The orienting response, the brain's reaction to novel and/or out of context familiar events, is reflected by the novelty P3 of the ERP. Contextually novel events also engender high rates of recognition memory. We examined, under incidental and intentional conditions, the effects of visual symbol familiarity on the novelty P3 recorded during an oddball task and on the parietal episodic memory (EM) effect, an index of recollection. Repetition of familiar, but not unfamiliar, symbols elicited a reduction in the novelty P3. Better recognition performance for the familiar symbols was associated with a robust parietal EM effect, which was absent for the unfamiliar symbols in the incidental task. These data demonstrate that processing of novel events depends on expectation and whether stimuli have preexisting representations in long-term semantic memory.

  3. Locomotor activity and tissue levels following acute ...

    EPA Pesticide Factsheets

    Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5 h after oral gavage dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29 mg/kg) compared to λ-cyhalothrin (2.65 mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administ

  4. Photic entrainment in Drosophila assessed by locomotor activity recordings.

    PubMed

    Schlichting, Matthias; Helfrich-Förster, Charlotte

    2015-01-01

    Light is the most important Zeitgeber to entrain the circadian clock of the fruit fly Drosophila melanogaster to the 24-h cycle on earth. The fruit fly's circadian clock is very light sensitive, mainly because about half of the 150 clock neurons in the fly's brain express the blue-light photopigment, Cryptochrome, which provokes an immediate degradation of the clock protein Timeless upon activation by light. Consequently, Drosophila's molecular clock can reset very fast to measure the changes in environmental-lighting conditions. However, usually the responses of the molecular clock to light are not directly measured, but conclusions about entrainment of the circadian clock are drawn from recording the flies' locomotor activity rhythms. Here, we review how the flies' locomotor activity can be recorded under different light regimes and how entrainment can be analyzed and properly judged. We also summarize the influence of different recording and lighting methods on the flies' activity pattern, highlight their advantages and disadvantages, and stress general pitfalls. © 2015 Elsevier Inc. All rights reserved.

  5. Effect of Environmental Conditions and Toxic Compounds on the Locomotor Activity of Pediculus humanus capitis (Phthiraptera: Pediculidae).

    PubMed

    Ortega-Insaurralde, I; Toloza, A C; Gonzalez-Audino, P; Mougabure-Cueto, G A; Alvarez-Costa, A; Roca-Acevedo, G; Picollo, M I

    2015-09-01

    In this work, we evaluated the effect of environmental variables such as temperature, humidity, and light on the locomotor activity of Pediculus humanus capitis. In addition, we used selected conditions of temperature, humidity, and light to study the effects of cypermethrin and N,N-diethyl-3-methylbenzamide (DEET) on the locomotor activity of head lice. Head lice increased their locomotor activity in an arena at 30°C compared with activity at 20°C. When we tested the influence of the humidity level, the locomotor activity of head lice showed no significant differences related to humidity level, both at 30°C and 20°C. Concerning light influence, we observed that the higher the intensity of light, the slower the movement of head lice. We also demonstrated that sublethal doses of toxics may alter locomotor activity in adults of head lice. Sublethal doses of cypermethrin induced hyperactivated responses in adult head lice. Sublethal doses of DEET evocated hypoactivated responses in head lice. The observation of stereotyped behavior in head lice elicited by toxic compounds proved that measuring locomotor activity in an experimental set-up where environmental conditions are controlled would be appropriate to evaluate compounds of biological importance, such as molecules involved in the host-parasite interaction and intraspecific relationships. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Both novelty and expertise increase action observation network activity

    PubMed Central

    Liew, Sook-Lei; Sheng, Tong; Margetis, John L.; Aziz-Zadeh, Lisa

    2013-01-01

    Our experiences with others affect how we perceive their actions. In particular, activity in bilateral premotor and parietal cortices during action observation, collectively known as the action observation network (AON), is modulated by one's expertise with the observed actions or individuals. However, conflicting reports suggest that AON activity is greatest both for familiar and unfamiliar actions. The current study examines the effects of different types and amounts of experience (e.g., visual, interpersonal, personal) on AON activation. fMRI was used to scan 16 healthy participants without prior experience with individuals with amputations (novices), 11 experienced occupational therapists (OTs) who had varying amounts of experience with individuals with amputations, and one individual born with below-elbow residual limbs (participant CJ), as they viewed video clips of goal-matched actions performed by an individual with residual limbs and by an individual with hands. Participants were given increased visual exposure to actions performed by both effectors midway through the scanning procedure. Novices demonstrated a large AON response to the initial viewing of an individual with residual limbs compared to one with hands, but this signal was attenuated after they received visual exposure to both effectors. In contrast, OTs, who had moderate familiarity with residual limbs, demonstrated a lower AON response upon initial viewing—similar to novices after they received visual exposure. At the other extreme, CJ, who has extreme familiarity with residual limbs both visually and motorically, shows a largely increased left-lateralized AON response, exceeding that of novices and experienced OTs, when viewing the residual limb compared to hand actions. These results suggest that a nuanced model of AON engagement is needed to explain how cases of both extreme experience (CJ) and extreme novelty (novices) can result in the greatest AON activity. PMID:24062656

  7. Light pulse duration differentially regulates mouse locomotor suppression and phase shifts.

    PubMed

    Morin, Lawrence P; Studholme, Keith M

    2014-10-01

    Brief exposure of mice to nocturnal light causes circadian rhythm phase shifts, simultaneously inducing locomotor suppression, a drop in body temperature, and associated sleep. The exact nature of the relationship between these light-induced responses is uncertain, although locomotor suppression and phase shift magnitudes are related to stimulus irradiance. Whether stimulus duration has similar effects is less clear. Here, the relationship between stimulus duration and response magnitude was evaluated further using 100 µW/cm(2) white light-emitting diode pulses administered for 30, 300, 1200, or 3000 sec. The results show that, in general, shorter pulses yielded smaller responses and larger pulses yielded larger responses. However, the 300-sec pulse failed to augment locomotor suppression compared with the effect of a 30-sec pulse (44.7 ± 4.8 vs 40.6 ± 2.0 min) but simultaneously induced much larger phase shifts (1.28 ± 0.20 vs 0.52 ± 0.11 h). The larger phase shifts induced by the 300-sec stimulus did not differ from those induced by either the 1200- or 3000-sec pulses (1.43 ± 0.10 and 1.30 ± 0.17 h, respectively). The results demonstrate differential photic regulation of the two response types. Pulses ranging from 300 to 3000 sec produce equal phase shifts (present data); pulses ranging from 30 to 600 sec produce equal locomotor suppression levels. Greater suppression can occur additively in response to pulses of 1200 sec or more (present data), but this is not true for phase shifts. Nocturnal light appears to trigger a fixed duration event, locomotor suppression, or phase shift, with the latter followed by a light-refractory interval during which locomotor suppression can additively increase. The results also provide further support for the view that temporal integration of photic energy applies, at best, across a limited set of stimulus durations for both light-induced locomotor suppression/sleep and phase shift regulation.

  8. Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human

    PubMed Central

    Ryczko, Dimitri; Dubuc, Réjean

    2017-01-01

    In vertebrates, dopamine neurons are classically known to modulate locomotion via their ascending projections to the basal ganglia that project to brainstem locomotor networks. An increased dopaminergic tone is associated with increase in locomotor activity. In pathological conditions where dopamine cells are lost, such as in Parkinson's disease, locomotor deficits are traditionally associated with the reduced ascending dopaminergic input to the basal ganglia. However, a descending dopaminergic pathway originating from the substantia nigra pars compacta was recently discovered. It innervates the mesencephalic locomotor region (MLR) from basal vertebrates to mammals. This pathway was shown to increase locomotor output in lampreys, and could very well play an important role in mammals. Here, we provide a detailed account on the newly found dopaminergic pathway in lamprey, salamander, rat, monkey, and human. In lampreys and salamanders, dopamine release in the MLR is associated with the activation of reticulospinal neurons that carry the locomotor command to the spinal cord. Dopamine release in the MLR potentiates locomotor movements through a D1-receptor mechanism in lampreys. In rats, stimulation of the substantia nigra pars compacta elicited dopamine release in the pedunculopontine nucleus, a known part of the MLR. In a monkey model of Parkinson's disease, a reduced dopaminergic innervation of the brainstem locomotor networks was reported. Dopaminergic fibers are also present in human pedunculopontine nucleus. We discuss the conserved locomotor role of this pathway from lamprey to mammals, and the hypothesis that this pathway could play a role in the locomotor deficits reported in Parkinson's disease. PMID:28603482

  9. The GABAB agonist baclofen blocks the expression of sensitisation to the locomotor stimulant effect of amphetamine.

    PubMed

    Bartoletti, M; Gubellini, C; Ricci, F; Gaiardi, M

    2004-09-01

    The purpose of the present study was to test the possible influence of baclofen, a GABAB agonist, on the long-term sensitisation to amphetamine in rats. As expected, chronic amphetamine treatment (1.5 mg/kg i.p. daily for 10 days) led to an increased locomotor response to amphetamine (0.75 mg/kg i.p.), when the animals were challenged 20 days after the end of repeated treatment. Baclofen (2 mg/kg i.p.), administered before the test session, did not significantly modify the spontaneous locomotor activity of rats, but decreased the normal and, to a greater extent, the sensitised locomotor response to amphetamine; thus baclofen prevented the expression of sensitisation to amphetamine. Moreover a previous chronic treatment with baclofen (2 mg/kg i.p. daily for 10 days) attenuated the amphetamine-induced locomotor activity in sensitised, but not in control animals. This effect was observed 20 days after the last baclofen administration. In conclusion, the present results demonstrate that GABAB receptors play an important role in the expression of the sensitised behavioural response to amphetamine and further support a potential role of GABAB agonists in the treatment of psychostimulant addiction.

  10. Novelty and Innovation in the History of Life.

    PubMed

    Erwin, Douglas H

    2015-10-05

    The history of life as documented by the fossil record encompasses evolutionary diversifications at scales ranging from the Ediacaran-Cambrian explosion of animal life and the invasion of land by vascular plants, insects and vertebrates to the diversification of flowering plants over the past 100 million years and the radiation of horses. Morphological novelty and innovation has been a recurrent theme. The architects of the modern synthesis of evolutionary theory made three claims about evolutionary novelty and innovation: first, that all diversifications in the history of life represent adaptive radiations; second, that adaptive radiations are driven principally by ecological opportunity rather than by the supply of new morphological novelties, thus the primary questions about novelty and innovation focus on their ecological and evolutionary success; and third, that the rate of morphological divergence between taxa was more rapid early in the history of a clade but slowed over time as ecological opportunities declined. These claims have strongly influenced subsequent generations of evolutionary biologists, yet over the past two decades each has been challenged by data from the fossil record, by the results of comparative phylogenetic analyses and through insights from evolutionary developmental biology. Consequently a broader view of novelty and innovation is required. An outstanding issue for future work is identifying the circumstances associated with different styles of diversification and whether their frequency has changed through the history of life.

  11. Auditory deviance detection revisited: evidence for a hierarchical novelty system.

    PubMed

    Grimm, Sabine; Escera, Carles

    2012-07-01

    The fast detection of novel or deviant stimuli is a striking property of the auditory processing which reflects basic organizational principles of the auditory system and at the same time is of high practical significance. In human electrophysiology, deviance detection has been related to the occurrence of the mismatch negativity (MMN)--a component of the event-related potential (ERP) evoked 100 to 250 ms after the occurrence of a rare irregular sound. Recently, it has been shown in animal studies that a considerable portion of neurons in the auditory pathway exhibits a property called stimulus-specific adaptation enabling them to encode inter-sound relationships and to discharge at higher rates to rare changes in the acoustic stimulation. These neural responses have been linked to the deviant-evoked potential measured at the human scalp, but such responses occur at lower levels anatomically (e.g. the primary auditory cortex as well as the inferior colliculi) and are elicited earlier (20-30 ms after sound onset) in comparison to MMN. Further, they are not considerable enough in size to be interpreted as a direct neural correlate of the MMN. We review here a series of recent findings that provides a first step toward filling this gap between animal and human recordings by showing that comparably early modulations due to a sound's deviancy can be observed in humans, particularly in the middle-latency portion of the ERP within the first 50 ms after sound onset. The existence of those early indices of deviance detection preceding the well-studied MMN component strongly supports the idea that the encoding of regularities and the detection of violations is a basic principle of human auditory processing acting on multiple levels. This sustains the notion of a hierarchically organized novelty and deviance detection system in the human auditory system.

  12. Male rats that differ in novelty exploration demonstrate distinct patterns of sexual behavior

    PubMed Central

    Cummings, Jennifer A.; Clinton, Sarah M.; Perry, Adam N.; Akil, Huda; Becker, Jill B.

    2014-01-01

    High versus low novelty exploration predicts a variety of behavioral differences. For example, rats selectively-bred for high novelty exploration (bred High Responders, bHR) exhibit exaggerated aggression, impulsivity, and proclivity to addictive behaviors compared to low novelty-reactive rats (bred Low Responders, bLRs), which are characterized by a high anxiety/depressive-like phenotype. Since bHR/bLR rats exhibit differences in dopaminergic circuitry and differential response to rewarding stimuli (i.e., psychostimulants, food), the present study examined whether they also differ in another key hedonic behavior – sex. Thus, adult bHR/bLR males were given five 30-min opportunities to engage in sexual activity with a receptive female. Sexual behavior and motivation were examined and compared between the groups. The bHR/bLR phenotype affected both sexual motivation and behavior, with bLR males demonstrating reduced motivation for sex compared with bHR males (i.e., fewer animals copulated, longer latency to engage in sex). The bHR males required more intromissions at a faster pace per ejaculation than did bLR males. Thus, neurobiological differences that affect motivation for drugs of abuse, aggression, and impulsivity in rats also affect sexual motivation and performance. PMID:23398441

  13. Novelty and Anxiolytic Drugs Dissociate Two Components of Hippocampal Theta in Behaving Rats

    PubMed Central

    Wells, Christine E.; Amos, Doran P.; Jeewajee, Ali; Douchamps, Vincent; Rodgers, John; O’Keefe, John; Burgess, Neil; Lever, Colin

    2013-01-01

    Hippocampal processing is strongly implicated in both spatial cognition and anxiety and is temporally organized by the theta rhythm. However, there has been little attempt to understand how each type of processing relates to the other in behaving animals, despite their common substrate. In freely moving rats, there is a broadly linear relationship between hippocampal theta frequency and running speed over the normal range of speeds used during foraging. A recent model predicts that spatial-translation-related and arousal/anxiety-related mechanisms of hippocampal theta generation underlie dissociable aspects of the theta frequency–running speed relationship (the slope and intercept, respectively). Here we provide the first confirmatory evidence: environmental novelty decreases slope, whereas anxiolytic drugs reduce intercept. Variation in slope predicted changes in spatial representation by CA1 place cells and novelty-responsive behavior. Variation in intercept predicted anxiety-like behavior. Our findings isolate and doubly dissociate two components of theta generation that operate in parallel in behaving animals and link them to anxiolytic drug action, novelty, and the metric for self-motion. PMID:23678110

  14. Influences of acute ethanol exposure on locomotor activities of zebrafish larvae under different illumination.

    PubMed

    Guo, Ning; Lin, Jia; Peng, Xiaolan; Chen, Haojun; Zhang, Yinglan; Liu, Xiuyun; Li, Qiang

    2015-11-01

    Larval zebrafish present unique opportunities to study the behavioral responses of a model organism to environmental challenges during early developmental stages. The purpose of the current study was to investigate the locomotor activities of AB strain zebrafish larvae at 5 and 7 days post-fertilization (dpf) in response to light changes under the influence of ethanol, and to explore potential neurological mechanisms that are involved in ethanol intoxication. AB strain zebrafish larvae at both 5 and 7 dpf were treated with ethanol at 0% (control), 0.1%, 0.25%, 0.5%, 1%, and 2% (v/v%). The locomotor activities of the larvae during alternating light-dark challenges, as well as the locomotor responses immediately following the light transitions, were investigated. The levels of various neurotransmitters were also measured in selected ethanol-treated groups. The larvae at 5 and 7 dpf demonstrated similar patterns of locomotor responses to ethanol treatment. Ethanol treatment at 1% increased the swimming distances of the zebrafish larvae in the dark periods, but had no effect on the swimming distances in the light periods. In contrast, ethanol treatment at 2% increased the swimming distances in the light periods, but did not potentiate the swimming activity in the dark periods, compared to controls. Differences in the levels of neurotransmitters that are involved in norepinephrine, dopamine, and serotonin pathways were also observed in groups with different ethanol treatments. These results indicated the behavioral studies concerning the ethanol effects on locomotor activities of zebrafish larvae could be carried out as early as 5 dpf. The 1% and 2% ethanol-treated zebrafish larvae modeled ethanol effects at different intoxication states, and the differences in neurotransmitter levels suggested the involvement of various neurotransmitter pathways in different ethanol intoxication states.

  15. Competition between novelty and cocaine conditioned reward is sensitive to drug dose and retention interval

    PubMed Central

    Reichel, Carmela M.; Bevins, Rick A.

    2010-01-01

    The following manuscript is the final accepted manuscript. It has not been subjected to the final copyediting, fact-checking, and proofreading required for formal publication. It is not the definitive, publisher-authenticated version. The American Psychological Association and its Council of Editors disclaim any responsibility or liabilities for errors or omissions of this manuscript version, any version derived from this manuscript by NIH, or other third parties. The published version is available at www.apa.org/pubs/journals/bne The conditioned rewarding effects of novelty compete with those of cocaine for control over choice behavior using a place-conditioning task. The purpose of the present study was to use multiple doses of cocaine to determine the extent of this competition and to determine whether novelty's impact on cocaine reward was maintained over an abstinence period. In Experiment 1, rats were conditioned with cocaine (7.5, 20, or 30 mg/kg, IP) to prefer one side of an unbiased place conditioning apparatus relative to the other. In a subsequent phase, all rats received alternating daily confinements to the previously cocaine-paired and unpaired sides of the apparatus. During this phase, half the rats had access to a novel object on their initially unpaired side; the remaining rats did not receive objects. The ability of novelty to compete with cocaine in a drug-free and cocaine-challenge test was sensitive to cocaine dose. In Experiment 2, a place preference was established with 10 mg/kg cocaine and testing occurred after 1, 14, or 28 day retention intervals. Findings indicate that choice behaviors mediated by cocaine conditioning are reduced with the passing of time. Taken together, competition between cocaine and novelty conditioned rewards are sensitive to drug dose and retention interval. PMID:20141289

  16. A parallel cholinergic brainstem pathway for enhancing locomotor drive

    PubMed Central

    Smetana, Roy; Juvin, Laurent; Dubuc, Réjean; Alford, Simon

    2010-01-01

    The brainstem locomotor system is believed to be organized serially from the mesencephalic locomotor region (MLR) to reticulospinal neurons, which in turn, project to locomotor neurons in the spinal cord. In contrast, we now identify in lampreys, brainstem muscarinoceptive neurons receiving parallel inputs from the MLR and projecting back to reticulospinal cells to amplify and extend durations of locomotor output. These cells respond to muscarine with extended periods of excitation, receive direct muscarinic excitation from the MLR, and project glutamatergic excitation to reticulospinal neurons. Targeted block of muscarine receptors over these neurons profoundly reduces MLR-induced excitation of reticulospinal neurons and markedly slows MLR-evoked locomotion. Their presence forces us to rethink the organization of supraspinal locomotor control, to include a sustained feedforward loop that boosts locomotor output. PMID:20473293

  17. Mephedrone interactions with cocaine: prior exposure to the 'bath salt' constituent enhances cocaine-induced locomotor activation in rats.

    PubMed

    Gregg, Ryan A; Tallarida, Christopher S; Reitz, Allen B; Rawls, Scott M

    2013-12-01

    Concurrent use of mephedrone (4-methylmethcathinone; MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity after pretreatment with cocaine or MEPH than after pretreatment with saline. METH challenge produced greater locomotor activity after METH pretreatment than after saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bidirectional and did not extend to METH, suggesting that the phenomenon is sensitive to specific psychostimulants.

  18. The development and expression of locomotor sensitization to nicotine in the presence of ibogaine.

    PubMed

    Zubaran, C; Shoaib, M; Stolerman, I P

    2000-08-01

    Ibogaine is a naturally occurring psychoactive alkaloid with claimed efficacy in the treatment of certain drug addictions, including nicotine. It has been reported to be a non-competitive blocker of nicotinic receptors, with a potent inhibitory action on nicotinic acetylcholine receptor-mediated catecholamine release. We have investigated the effect of different doses of ibogaine on the development and expression of sensitization to the locomotor stimulant effect of nicotine in rats, a facilitatory process in which a history of exposure to nicotine results in enhanced locomotor activity when the same dose of nicotine is administered repeatedly. The effects were determined of co-administering ibogaine (0.0, 5.0 or 10 mg/kg i.p.) with nicotine (0.0 or 0.4 mg/kg s.c.) daily for 21 days. Dose-response curves for nicotine (0.04-0.8 mg/kg s.c.) were then determined in groups of 10 rats. There was clear sensitization of the locomotor activity produced by nicotine in photocell activity cages but co-administration of ibogaine with nicotine had no effect on the degree of sensitization. Ibogaine (5-20 mg/kg) itself did not influence locomotor activity and was also without effect on the expression of the sensitized response to 0.4 mg/kg of nicotine (n = 10). Thus, there was no evidence that ibogaine may retard or suppress sensitization to nicotine.

  19. Decreased plasma ghrelin contributes to anorexia following novelty stress.

    PubMed

    Saegusa, Yayoi; Takeda, Hiroshi; Muto, Shuichi; Nakagawa, Koji; Ohnishi, Shunsuke; Sadakane, Chiharu; Nahata, Miwa; Hattori, Tomohisa; Asaka, Masahiro

    2011-10-01

    We hypothesized that anorexia induced by novelty stress caused by exposure to a novel environment may be due to activation of corticotropin-releasing factor (CRF) and subsequently mediated by decreasing peripheral ghrelin concentration via serotonin (5-HT) and melanocortin-4 receptors (MC4R). Each mouse was transferred from group-housed cages to individual cages to establish the novelty stress. We observed the effect of changes in feeding behavior in a novel environment using the method of transferring group-housed mice to individual cages. We investigated the effect of an intracerebroventricular injection of antagonists/agonists of CRF1/2 receptors (CRF1/2Rs), 5-HT(1B)/(2C) receptors (5-HT(1B)/(2C)R), and MC4R to clarify the role of each receptor on the decrease in food intake. Plasma ghrelin levels were also measured. The novelty stress caused a reduction in food intake that was abolished by administering a CRF1R antagonist. Three hours after the novelty stress, appetite reduction was associated with reduced levels of neuropeptide Y/agouti-related peptide mRNA, increased levels of proopiomelanocortin mRNA in the hypothalamus, and a decrease in plasma ghrelin level. Administering a CRF1R antagonist, a 5-HT(1B)/(2C)R antagonist, an MC4R antagonist, exogenous ghrelin, and an enhancer of ghrelin secretion, rikkunshito, resolved the reduction in food intake 3 h after the novelty stress by enhancing circulating ghrelin concentrations. We showed that anorexia during a novelty stress is a process in which CRF1R is activated at the early stage of appetite loss and is subsequently activated by a 5-HT(1B)/(2C)R and MC4R stimulus, leading to decreased peripheral ghrelin concentrations.

  20. Escalation of food-maintained responding and sensitivity to the locomotor stimulant effects of cocaine in mice.

    PubMed

    Goeders, James E; Murnane, Kevin S; Banks, Matthew L; Fantegrossi, William E

    2009-07-01

    Escalation of drug self-administration is a consequence of extended drug access and is thought to be specifically related to addiction, but few studies have investigated whether intake of non-drug reinforcers may also escalate with extended-access. The goal of these studies was to determine the effects of limited and extended-access to food reinforcers on behavioral and pharmacological endpoints in mice. In distinct groups, responding on a lever was maintained by liquid reinforcement, or nose-poke responses were maintained by sucrose pellets or liquid food in sessions lasting 1 h (limited-access) or 10 h (extended-access). The reinforcing strength of each food, as well as reinforcer-associated cues, was tested before and after extended-access using a progressive ratio (PR) schedule, and locomotor activity in response to novelty and increasing doses of cocaine was assessed in an open field setting in all animals after access to food reinforcers. Escalation of lever-pressing behavior reinforced by liquid food, but not nose-poke behavior reinforced by liquid food or sucrose pellets, was observed across successive extended-access sessions. A concomitant increase in the reinforcing strength of liquid food and its associated cues was apparent in mice that escalated their responding, but not in mice that did not escalate. Finally, extended reinforcer access leading to behavioral escalation was accompanied by an increased sensitivity to the psychostimulant effects of cocaine compared to limited-access. These findings indicate that behavioral escalation can develop as a consequence of extended-access to a non-drug reinforcer, although both the nature of the reinforcer (liquid versus solid food) and the topography of the operant response (lever versus nose-poke) modulate its development. These data also suggest that some of the behavioral and pharmacological corrolaries of behavioral escalation observed following extended-access to drug self-administration may not be due to

  1. Modelling the locomotor energetics of extinct hominids.

    PubMed

    Kramer, P A

    1999-10-01

    Bipedality is the defining characteristic of Hominidae and, as such, an understanding of the adaptive significance and functional implications of bipedality is imperative to any study of human evolution. Hominid bipedality is, presumably, a solution to some problem for the early hominids, one that has much to do with energy expenditure. Until recently, however, little attention could be focused on the quantifiable energetic aspects of bipedality as a unique locomotor form within Primates because of the inability to measure empirically the energy expenditure of non-modern hominids. A recently published method provides a way of circumventing the empirical measurement dilemma by calculating energy expenditure directly from anatomical variables and movement profiles. Although the origins of bipedality remain clouded, two discernible forms of locomotor anatomy are present in the hominid fossil record: the australopithecine and modern configurations. The australopithecine form is best represented by AL 288-1, a partial skeleton of Australopithecus afarensis, and is characterized as having short legs and a wide pelvis. The modern form is represented by modern humans and has long legs and a narrow pelvis. Human walking is optimized to take advantage of the changing levels of potential and kinetic energy that occur as the body and limbs move through the stride cycle. Although this optimization minimizes energy expenditure, some energy is required to maintain motion. I quantify this energy by developing a dynamic model that uses kinematic equations to determine energy expenditure. By representing both configurations with such a model, I can compare their rates of energy expenditure. I find that the australopithecine configuration uses less energy than that of a modern human. Despite arguments presented in the anthropological literature, the shortness of the legs of AL 288-1 provides no evidence that she was burdened with a compromised or transitional locomotor anatomy

  2. Lack of locomotor-cardiac coupling in trotting dogs.

    PubMed

    Simmons, A D; Carrier, D R; Farmer, C G; Gregersen, C S

    1997-10-01

    Coupling of locomotor and cardiac cycles has been suggested to facilitate effective arterial delivery and venous return during vigorous exercise. In an attempt to document locomotor-cardiac coupling, we ran five dogs on a motorized treadmill while monitoring heart activity with surface electrocardiogram electrodes and locomotor events with high-speed video and an accelerometer mounted on the dog's back. Analysis of the cardiac and locomotor frequencies revealed that heart rate was usually slightly greater than stride frequency. Hence the timing of the cardiac cycles varied with respect to the phase of the locomotor cycles, and therefore consistent coupling of the locomotor and cardiac cycles was not observed in any of the dogs. However, the period of the cardiac cycle sometimes varied in a rhythmic way that caused brief periods of transient coupling of the locomotor and cardiac cycles in three of the five dogs. These brief periods of coupling (5-20 heartbeats) occurred at approximately the same phase relationship in each of the three dogs. We hypothesize that the variation in cardiac period and the resulting transient coupling are a function of locomotor and ventilatory influences on venous return and/or ventricular ejection. Because venous return and ejection fraction are likely to vary in an unpredictable manner when animals run in a complex environment, we suggest that reflex control of heart rate will be important during locomotion and strict integer coupling of the locomotor and cardiac cycles is unlikely to evolve.

  3. The D₂ dopamine receptor and locomotor hyperactivity following bilateral vestibular deafferentation in the rat.

    PubMed

    Stiles, Lucy; Zheng, Yiwen; Darlington, Cynthia L; Smith, Paul F

    2012-02-01

    Rats and mice with bilateral vestibular loss exhibit dramatic locomotor hyperactivity and circling behaviours, which to date cannot be explained. Dysfunction of the striatal dopaminergic system is responsible for a number of known movement disorders and the D(2) dopamine receptor is known to be implicated. Therefore, it is possible that changes in striatal function are responsible for locomotor hyperactivity and circling following bilateral vestibular lesions. The aim of this study was to investigate the effects of the D(2) receptor antagonist, eticlopride (0.02, 0.04 and 0.06mg/kg; s.c.), on locomotor behaviour in rats at 5 months following bilateral vestibular deafferentation (BVD), using an open field maze. The levels of the D(2) receptor protein in the striatum were measured at 1 and 6 months post-BVD using western blotting. BVD rats exhibited locomotor hyperactivity and circling, which eticlopride did not eliminate. However, BVD rats did exhibit a decreased response to the inhibitory effect of eticlopride compared to sham controls at the 0.02 mg/kg dose. There were no changes in the amount of the D(2) receptor in the striatum at 1 or 6 months post-BVD; however, D(2) receptor levels were significantly higher on the right side than the left in both sham and BVD animals. These results suggest that locomotor hyperactivity and circling behaviours following BVD are not due simply to changes in D(2) receptor protein expression in the striatum and that other neurophysiological changes in the brain account for these behaviours following BVD.

  4. Evaluation of unconditioned novelty-seeking and d-amphetamine-conditioned motivation in mice.

    PubMed

    Laviola, G; Adriani, W

    1998-04-01

    Following repeated association between psychostimulant drugs and a distinct environment, contextual cues acquire the ability to elicit a conditioned approach response. Further, both rats and mice have a natural drive to seek for the experience of novelty, and a previously unknown environment is able to elicit an unconditioned approach response. Both the experience of novelty and amphetamine (AMPH)-conditioned effects have been associated in rodents with the activation of brain meso-limbic dopaminergic pathways. This study assessed the relative strength of AMPH-conditioned and novelty-induced unconditioned motivations in mice. During the pretreatment period, mice were randomly assigned to three different treatment history groups, and received d-AMPH (0, 2, or 10 mg/kg i.p. once/day) injections for 3 days in the presence of a familiar environment. Following a 48-h washout from the last drug injection, animals were placed in the familiar and pretreatment-paired environment and challenged with either SAL (to evaluate conditioning) or a standard AMPH dose (2 mg/kg, to assess either acute drug effects or carryover influences of each animal's treatment history with the same drug). Following the opening of a partition, animals showed both a clear-cut preference for a novel environment as well as a marked novelty-induced hyperactivity. Interestingly, when mice were tested in a drug-free state in this free-choice paradigm, they expressed neither conditioning to the drug-associated environment nor carry-over effects on the novelty-induced hyperactivity profile. On the other hand, mice injected with AMPH showed a mixed profile, with AMPH 2 treatment history mice showing a conditioned preference for the familiar and drug-paired environment, whereas AMPH 10 animals preferred to spend more time in the novel compartment. Both AMPH doses were associated with an increased locomotion, whereas only the AMPH 10 dose resulted in a stereotyped behavioral syndrome, possibly reminiscent of

  5. Unpredictable saccharin reinforcement enhances locomotor responding to amphetamine.

    PubMed

    Singer, B F; Scott-Railton, J; Vezina, P

    2012-01-01

    Drug-naïve, non-deprived rats were trained to lever press for saccharin under fixed-ratio (FR) or variable-ratio (VR) schedules of reinforcement. Rats trained on the VR schedule in which saccharin reinforcement was not predicted by a fixed number of lever presses subsequently showed an enhanced locomotor response to a threshold amphetamine challenge injection (0.5mg/kg IP) administered 2 weeks following the last saccharin session. This finding suggests that chronic exposure to gambling-like conditions of uncertain reinforcement can induce neuroadaptations in brain reward systems that are similar to those produced by repeated psychostimulant exposure and may lead to the development of addictive behaviors. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Infants prefer the faces of strangers or mothers to morphed faces: an uncanny valley between social novelty and familiarity.

    PubMed

    Matsuda, Yoshi-Taka; Okamoto, Yoko; Ida, Misako; Okanoya, Kazuo; Myowa-Yamakoshi, Masako

    2012-10-23

    The 'uncanny valley' response is a phenomenon involving the elicitation of a negative feeling and subsequent avoidant behaviour in human adults and infants as a result of viewing very realistic human-like robots or computer avatars. It is hypothesized that this uncanny feeling occurs because the realistic synthetic characters elicit the concept of 'human' but fail to satisfy it. Such violations of our normal expectations regarding social signals generate a feeling of unease. This conflict-induced uncanny valley between mutually exclusive categories (human and synthetic agent) raises a new question: could an uncanny feeling be elicited by other mutually exclusive categories, such as familiarity and novelty? Given that infants prefer both familiarity and novelty in social objects, we address this question as well as the associated developmental profile. Using the morphing technique and a preferential-looking paradigm, we demonstrated uncanny valley responses of infants to faces of mothers (i.e. familiarity) and strangers (i.e. novelty). Furthermore, this effect strengthened with the infant's age. We excluded the possibility that infants detect and avoid traces of morphing. This conclusion follows from our finding that the infants equally preferred strangers' faces and the morphed faces of two strangers. These results indicate that an uncanny valley between familiarity and novelty may accentuate the categorical perception of familiar and novel objects.

  7. The genetic architecture of behavioural responses to novelty in mice.

    PubMed

    Crusio, W E; van Abeelen, J H

    1986-02-01

    The genetic architectures of 12 behavioural variables measured in adult male mice placed in a novel environment were analysed in a replicated 4 X 4 diallel cross. The results were combined with those obtained in a classical cross involving two of the four strains. Based on the hypothesis of an evolutionary history of stabilising selection for mouse exploratory behaviour, we expected additive genetic effects and ambidirectional dominance. Such genetic architectures were actually found for those exploratory behaviours where epistatic effects were of minor importance. Similar findings emerged for some non-exploratory phenotypes. All behaviours analysed appeared to be polygenically controlled.

  8. Voluntary and reactive recruitment of locomotor muscle synergies during perturbed walking.

    PubMed

    Chvatal, Stacie A; Ting, Lena H

    2012-08-29

    The modular control of muscles in groups, often referred to as muscle synergies, has been proposed to provide a motor repertoire of actions for the robust control of movement. However, it is not clear whether muscle synergies identified in one task are also recruited by different neural pathways subserving other motor behaviors. We tested the hypothesis that voluntary and reactive modifications to walking in humans result from the recruitment of locomotor muscle synergies. We recorded the activity of 16 muscles in the right leg as subjects walked a 7.5 m path at two different speeds. To elicit a second motor behavior, midway through the path we imposed ramp and hold translation perturbations of the support surface in each of four cardinal directions. Variations in the temporal recruitment of locomotor muscle synergies could account for cycle-by-cycle variations in muscle activity across strides. Locomotor muscle synergies were also recruited in atypical phases of gait, accounting for both anticipatory gait modifications before perturbations and reactive feedback responses to perturbations. Our findings are consistent with the idea that a common pool of spatially fixed locomotor muscle synergies can be recruited by different neural pathways, including the central pattern generator for walking, brainstem pathways for balance control, and cortical pathways mediating voluntary gait modifications. Together with electrophysiological studies, our work suggests that muscle synergies may provide a library of motor subtasks that can be flexibly recruited by parallel descending pathways to generate a variety of complex natural movements in the upper and lower limbs.

  9. Prenatal Cocaine Exposure and Infants' Preference for Novelty and Distractibility

    ERIC Educational Resources Information Center

    Gaultney, Jane F.; Gingras, Jeannine L.; Martin, Mindy; DeBrule, Daniel

    2005-01-01

    The authors used the Fagan Test of Infant Intelligence (J. F. Fagan, L. T. Singer, J. E. Montie, & P. A. Shepherd, 1986) to examine preferences for novelty and to evaluate several indicators of attention (off- and on-task indexes and durations) in 6- and 9-month-old infants who had been prenatally exposed to cigarette smoke only or to cocaine plus…

  10. Secondary contact seeds phenotypic novelty in cichlid fishes

    PubMed Central

    Nichols, Paul; Genner, Martin J.; van Oosterhout, Cock; Smith, Alan; Parsons, Paul; Sungani, Harold; Swanstrom, Jennifer; Joyce, Domino A.

    2015-01-01

    Theory proposes that genomic admixture between formerly reproductively isolated populations can generate phenotypic novelty for selection to act upon. Secondary contact may therefore be a significant promoter of phenotypic novelty that allows species to overcome environmental challenges and adapt to novel environments, including during adaptive radiation. To date, this has largely been considered from the perspective of interspecific hybridization at contact zones. However, it is also possible that this process occurs more commonly between natural populations of a single species, and thus its importance in adaptive evolution may have been underestimated. In this study, we tested the consequences of genomic introgression during apparent secondary contact between phenotypically similar lineages of the riverine cichlid fish Astatotilapia calliptera. We provide population genetic evidence of a secondary contact zone in the wild, and then demonstrate using mate-choice experiments that both lineages can reproduce together successfully in laboratory conditions. Finally, we show that genomically admixed individuals display extreme phenotypes not observed in the parental lineages. Collectively, the evidence shows that secondary contact can drive the evolution of phenotypic novelty, suggesting that pulses of secondary contact may repeatedly seed genetic novelty, which when coupled with ecological opportunity could promote rapid adaptive evolution in natural circumstances. PMID:25392475

  11. Secondary contact seeds phenotypic novelty in cichlid fishes.

    PubMed

    Nichols, Paul; Genner, Martin J; van Oosterhout, Cock; Smith, Alan; Parsons, Paul; Sungani, Harold; Swanstrom, Jennifer; Joyce, Domino A

    2015-01-07

    Theory proposes that genomic admixture between formerly reproductively isolated populations can generate phenotypic novelty for selection to act upon. Secondary contact may therefore be a significant promoter of phenotypic novelty that allows species to overcome environmental challenges and adapt to novel environments, including during adaptive radiation. To date, this has largely been considered from the perspective of interspecific hybridization at contact zones. However, it is also possible that this process occurs more commonly between natural populations of a single species, and thus its importance in adaptive evolution may have been underestimated. In this study, we tested the consequences of genomic introgression during apparent secondary contact between phenotypically similar lineages of the riverine cichlid fish Astatotilapia calliptera. We provide population genetic evidence of a secondary contact zone in the wild, and then demonstrate using mate-choice experiments that both lineages can reproduce together successfully in laboratory conditions. Finally, we show that genomically admixed individuals display extreme phenotypes not observed in the parental lineages. Collectively, the evidence shows that secondary contact can drive the evolution of phenotypic novelty, suggesting that pulses of secondary contact may repeatedly seed genetic novelty, which when coupled with ecological opportunity could promote rapid adaptive evolution in natural circumstances.

  12. Emergent Novelties in the Mentality of Dizygotic Twins.

    ERIC Educational Resources Information Center

    Bierschenk, Bernhard

    Scanator is an extremely valuable tool in the functional analysis of qualitative stability in text building behavior during writing. Scanator also allows for a detailed investigation of subtle changes emerging in the structural relations of emergent novelties. This study focused on the extension of the application of Scanator to one pair of…

  13. High Novelty-Seeking Rats Are Resilient to Negative Physiological Effects of the Early Life Stress

    PubMed Central

    Clinton, Sarah M.; Watson, Stanley J.; Akil, Huda

    2014-01-01

    Exposure to early life stress dramatically impacts adult behavior, physiology, and neuroendocrine function. Using rats bred for novelty-seeking differences and known to display divergent anxiety, depression, and stress vulnerability, we examined the interaction between early life adversity and genetic predisposition for high- versus low-emotional reactivity. Thus, bred Low Novelty Responder (bLR) rats, which naturally exhibit high anxiety- and depression-like behavior, and bred High Novelty Responder (bHR) rats, which show low anxiety/depression together with elevated aggression, impulsivity, and addictive behavior, were subjected to daily 3 h maternal separation (MS) stress postnatal days 1–14. We hypothesized that MS stress would differentially impact adult bHR/bLR behavior, physiology (stress-induced defecation), and neuroendocrine reactivity. While MS stress did not impact bHR and bLR anxiety-like behavior in the open field test and elevated plus maze, it exacerbated bLRs’ already high physiological response to stress – stress-induced defecation. In both tests, MS bLR adult offspring showed exaggerated stress-induced defecation compared to bLR controls while bHR offspring were unaffected. MS also selectively impacted bLRs’ (but not bHRs’) neuroendocrine stress reactivity, producing an exaggerated corticosterone acute stress response in MS bLR versus control bLR rats. These findings highlight how genetic predisposition shapes individuals’ response to early life stress. Future work will explore neural mechanisms underlying the distinct behavioral and neuroendocrine consequences of MS in bHR/bLR animals. PMID:24090131

  14. High novelty-seeking rats are resilient to negative physiological effects of the early life stress.

    PubMed

    Clinton, Sarah M; Watson, Stanley J; Akil, Huda

    2014-01-01

    Exposure to early life stress dramatically impacts adult behavior, physiology, and neuroendocrine function. Using rats bred for novelty-seeking differences and known to display divergent anxiety, depression, and stress vulnerability, we examined the interaction between early life adversity and genetic predisposition for high- versus low-emotional reactivity. Thus, bred Low Novelty Responder (bLR) rats, which naturally exhibit high anxiety- and depression-like behavior, and bred High Novelty Responder (bHR) rats, which show low anxiety/depression together with elevated aggression, impulsivity, and addictive behavior, were subjected to daily 3 h maternal separation (MS) stress postnatal days 1-14. We hypothesized that MS stress would differentially impact adult bHR/bLR behavior, physiology (stress-induced defecation), and neuroendocrine reactivity. While MS stress did not impact bHR and bLR anxiety-like behavior in the open field test and elevated plus maze, it exacerbated bLRs' already high physiological response to stress - stress-induced defecation. In both tests, MS bLR adult offspring showed exaggerated stress-induced defecation compared to bLR controls while bHR offspring were unaffected. MS also selectively impacted bLRs' (but not bHRs') neuroendocrine stress reactivity, producing an exaggerated corticosterone acute stress response in MS bLR versus control bLR rats. These findings highlight how genetic predisposition shapes individuals' response to early life stress. Future work will explore neural mechanisms underlying the distinct behavioral and neuroendocrine consequences of MS in bHR/bLR animals.

  15. Locomotor behaviour of Blattella germanica modified by DEET.

    PubMed

    Sfara, Valeria; Mougabure-Cueto, Gastón A; Zerba, Eduardo N; Alzogaray, Raúl A

    2013-01-01

    N,N-diethyl-3-methylbenzamide (DEET) is the active principle of most insect repellents used worldwide. However, its toxicity on insects has not been widely studied. The aim of this work is to study the effects of DEET on the locomotor activity of Blattella germanica. DEET has a dose-dependent repellent activity on B. germanica. Locomotor activity was significantly lower when insects were pre-exposed to 700 µg/cm(2) of DEET for 20 or 30 minutes, but it did not change when pre-exposure was shorter. Locomotor activity of insects that were pre-exposed to 2.000 µg/cm(2) of DEET for 10 minutes was significantly lower than the movement registered in controls. No differences were observed when insects were pre-exposed to lower concentrations of DEET. A 30-minute pre-exposure to 700 µg/cm(2) of DEET caused a significant decrease in locomotor activity. Movement was totally recovered 24 h later. The locomotor activity measured during the exposure to different concentrations of DEET remained unchanged. Insects with decreased locomotor activity were repelled to the same extent than control insects by the same concentration of DEET. We demonstrated that the repellency and modification of locomotor activity elicited by DEET are non-associated phenomena. We also suggested that the reduction in locomotor activity indicates toxicity of DEET, probably to insect nervous system.

  16. Locomotor Behaviour of Blattella germanica Modified by DEET

    PubMed Central

    Sfara, Valeria; Mougabure-Cueto, Gastón A.; Zerba, Eduardo N.; Alzogaray, Raúl A.

    2013-01-01

    N,N-diethyl-3-methylbenzamide (DEET) is the active principle of most insect repellents used worldwide. However, its toxicity on insects has not been widely studied. The aim of this work is to study the effects of DEET on the locomotor activity of Blattella germanica. DEET has a dose-dependent repellent activity on B. germanica. Locomotor activity was significantly lower when insects were pre-exposed to 700 µg/cm2 of DEET for 20 or 30 minutes, but it did not change when pre-exposure was shorter. Locomotor activity of insects that were pre-exposed to 2.000 µg/cm2 of DEET for 10 minutes was significantly lower than the movement registered in controls. No differences were observed when insects were pre-exposed to lower concentrations of DEET. A 30-minute pre-exposure to 700 µg/cm2 of DEET caused a significant decrease in locomotor activity. Movement was totally recovered 24 h later. The locomotor activity measured during the exposure to different concentrations of DEET remained unchanged. Insects with decreased locomotor activity were repelled to the same extent than control insects by the same concentration of DEET. We demonstrated that the repellency and modification of locomotor activity elicited by DEET are non-associated phenomena. We also suggested that the reduction in locomotor activity indicates toxicity of DEET, probably to insect nervous system. PMID:24376701

  17. Melatonin and locomotor activity in the fiddler crab Uca pugilator.

    PubMed

    Tilden, Andrea R; Shanahan, J Kearney; Khilji, Zahra S; Owen, Jeffrey G; Sterio, Thomas W; Thurston, Kristy T

    2003-05-01

    The influence of melatonin on locomotor activity levels was measured in the fiddler crab Uca pugilator. First, activity in untreated, laboratory-acclimated crabs was measured over 48 hours in a 12L:12D photoperiod; this study showed a nocturnal increase in activity. In eyestalk-ablated crabs, overall activity was significantly reduced, and no significant activity pattern occurred. Next, crabs were injected with melatonin or saline (controls) at various times during the 12L:12D photoperiod (0900h, 1200h, and twice at 2100h; each trial was separated by 3-4 days) and monitored for 3 hr post-injection. Control crabs had low activity during early photophase, high at mid-photophase, increasing activity during the first scotophase trial, and decreasing activity during the second scotophase trial. Melatonin had no significant influence on activity when injected during the early-photophase activity trough or early-scotophase activity decline, but significantly increased activity when injected during the mid-photophase activity peak and early-scotophase activity incline. Next, crabs were injected during an early scotophase activity trough and monitored throughout the twelve-hour scotophase. Melatonin did not increase activity until the mid-scotophase activity increase, approximately 6 hours later, showing that the pharmacological dosage persisted in the crabs' systems and had later effects during the incline and peak of activity but not the trough. Eyestalk-ablated crabs were injected with melatonin or saline during early photo- and scotophase. Melatonin significantly increased activity in the photophase but not the scotophase trial, indicating that the responsiveness to melatonin continues following eyestalk removal, but the timing may not match that of intact crabs. Melatonin may be involved in the transmission of environmental timing information from the eyestalks to locomotor centers in U. pugilator.

  18. Aesthetic Emotions and Aesthetic People: Openness Predicts Sensitivity to Novelty in the Experiences of Interest and Pleasure.

    PubMed

    Fayn, Kirill; MacCann, Carolyn; Tiliopoulos, Niko; Silvia, Paul J

    2015-01-01

    There is a stable relationship between the Openness/Intellect domain of personality and aesthetic engagement. However, neither of these are simple constructs and while the relationship exists, process based evidence explaining the relationship is still lacking. This research sought to clarify the relationship by evaluating the influence of the Openness and Intellect aspects on several different aesthetic emotions. Two studies looked at the between- and within-person differences in arousal and the emotions of interest, pleasure and confusion in response to visual art. The results suggest that Openness, as opposed to Intellect, was predictive of greater arousal, interest and pleasure, while both aspects explained less confusion. Differences in Openness were associated with within-person emotion appraisal contingencies, particularly greater novelty-interest and novelty-pleasure relationships. Those higher in Openness were particularly influenced by novelty in artworks. For pleasure this relationship suggested a different qualitative structure of appraisals. The appraisal of novelty is part of the experience of pleasure for those high in Openness, but not those low in Openness. This research supports the utility of studying Openness and Intellect as separate aspects of the broad domain and clarifies the relationship between Openness and aesthetic states in terms of within-person appraisal processes.

  19. Aesthetic Emotions and Aesthetic People: Openness Predicts Sensitivity to Novelty in the Experiences of Interest and Pleasure

    PubMed Central

    Fayn, Kirill; MacCann, Carolyn; Tiliopoulos, Niko; Silvia, Paul J.

    2015-01-01

    There is a stable relationship between the Openness/Intellect domain of personality and aesthetic engagement. However, neither of these are simple constructs and while the relationship exists, process based evidence explaining the relationship is still lacking. This research sought to clarify the relationship by evaluating the influence of the Openness and Intellect aspects on several different aesthetic emotions. Two studies looked at the between- and within-person differences in arousal and the emotions of interest, pleasure and confusion in response to visual art. The results suggest that Openness, as opposed to Intellect, was predictive of greater arousal, interest and pleasure, while both aspects explained less confusion. Differences in Openness were associated with within-person emotion appraisal contingencies, particularly greater novelty-interest and novelty-pleasure relationships. Those higher in Openness were particularly influenced by novelty in artworks. For pleasure this relationship suggested a different qualitative structure of appraisals. The appraisal of novelty is part of the experience of pleasure for those high in Openness, but not those low in Openness. This research supports the utility of studying Openness and Intellect as separate aspects of the broad domain and clarifies the relationship between Openness and aesthetic states in terms of within-person appraisal processes. PMID:26696940

  20. EEG delta oscillations index inhibitory control of contextual novelty to both irrelevant distracters and relevant task-switch cues.

    PubMed

    Prada, Laura; Barceló, Francisco; Herrmann, Christoph S; Escera, Carles

    2014-07-01

    Delta oscillations contribute to the human P300 event-related potential evoked by oddball targets, although it is unclear whether they index contextual novelty (event oddballness, novelty P3, nP3), or target-related processes (event targetness, target P3b). To examine this question, the electroencephalogram (EEG) was recorded during a cued task-switching version of the Wisconsin card-sorting test. Each target card was announced by a tone cueing either to switch or repeat the task. Novel sound distracters were interspersed among trials. Time-frequency EEG analyses revealed bursts of delta (2-4 Hz) power associated with enhanced nP3 amplitudes to both task-switch cues and novel distracters-but no association with target P3b. These findings indicate that the P300-delta response indexes contextual novelty regardless of whether novelty emanates from endogenous (new task rules) or exogenous (novel distracters) sources of information. Copyright © 2014 Society for Psychophysiological Research.

  1. Towards a cognitive model of distraction by auditory novelty: the role of involuntary attention capture and semantic processing.

    PubMed

    Parmentier, Fabrice B R

    2008-12-01

    Unexpected auditory stimuli are potent distractors, able to break through selective attention and disrupt performance in an unrelated visual task. This study examined the processing fate of novel sounds by examining the extent to which their semantic content is analyzed and whether the outcome of this processing can impact on subsequent behavior. This issue was investigated across five laboratory experiments in which participants categorized visual left and right arrows while instructed to ignore irrelevant sounds. The results showed that auditory novels that were incongruent with the visual target (e.g., word "left" presented before a right arrow) disrupted performance over and above congruent novels (semantic effect) while both types of novels delayed responses in the visual task compared to a standard sound (novelty effect). No semantic effect was observed for congruent and incongruent standards, suggesting that novelty detection is necessary for involuntary semantic processing to unravel. While the novelty effect augmented as the difference between novels and the standard increased, the semantic effect was immune to this variation. Furthermore, the novelty effect decreased across the task while the semantic effect did not. A general cognitive framework is proposed encompassing these new findings and previous work in an attempt to account for the behavioral impact of irrelevant auditory novels on primary task performance.

  2. A silent synapse-based mechanism for cocaine-induced locomotor sensitization.

    PubMed

    Brown, Travis E; Lee, Brian R; Mu, Ping; Ferguson, Deveroux; Dietz, David; Ohnishi, Yoshinori N; Lin, Ying; Suska, Anna; Ishikawa, Masago; Huang, Yanhua H; Shen, Haowei; Kalivas, Peter W; Sorg, Barbara A; Zukin, R Suzanne; Nestler, Eric J; Dong, Yan; Schlüter, Oliver M

    2011-06-01

    Locomotor sensitization is a common and robust behavioral alteration in rodents whereby following exposure to abused drugs such as cocaine, the animal becomes significantly more hyperactive in response to an acute drug challenge. Here, we further analyzed the role of cocaine-induced silent synapses in the nucleus accumbens (NAc) shell and their contribution to the development of locomotor sensitization. Using a combination of viral vector-mediated genetic manipulations, biochemistry, and electrophysiology in a locomotor sensitization paradigm with repeated, daily, noncontingent cocaine (15 mg/kg) injections, we show that dominant-negative cAMP-element binding protein (CREB) prevents cocaine-induced generation of silent synapses of young (30 d old) rats, whereas constitutively active CREB is sufficient to increase the number of NR2B-containing NMDA receptors (NMDARs) at synapses and to generate silent synapses. We further show that occupancy of CREB at the NR2B promoter increases and is causally related to the increase in synaptic NR2B levels. Blockade of NR2B-containing NMDARs by administration of the NR2B-selective antagonist Ro256981 directly into the NAc, under conditions that inhibit cocaine-induced silent synapses, prevents the development of cocaine-elicited locomotor sensitization. Our data are consistent with a cellular cascade whereby cocaine-induced activation of CREB promotes CREB-dependent transcription of NR2B and synaptic incorporation of NR2B-containing NMDARs, which generates new silent synapses within the NAc. We propose that cocaine-induced activation of CREB and generation of new silent synapses may serve as key cellular events mediating cocaine-induced locomotor sensitization. These findings provide a novel cellular mechanism that may contribute to cocaine-induced behavioral alterations.

  3. Functional Reorganization of the Locomotor Network in Parkinson Patients with Freezing of Gait

    PubMed Central

    Fling, Brett W.; Cohen, Rajal G.; Mancini, Martina; Carpenter, Samuel D.; Fair, Damien A.; Nutt, John G.; Horak, Fay B.

    2014-01-01

    Freezing of gait (FoG) is a transient inability to initiate or maintain stepping that often accompanies advanced Parkinson’s disease (PD) and significantly impairs mobility. The current study uses a multimodal neuroimaging approach to assess differences in the functional and structural locomotor neural network in PD patients with and without FoG and relates these findings to measures of FoG severity. Twenty-six PD patients and fifteen age-matched controls underwent resting-state functional magnetic resonance imaging and diffusion tensor imaging along with self-reported and clinical assessments of FoG. After stringent movement correction, fifteen PD patients and fourteen control participants were available for analysis. We assessed functional connectivity strength between the supplementary motor area (SMA) and the following locomotor hubs: 1) subthalamic nucleus (STN), 2) mesencephalic and 3) cerebellar locomotor region (MLR and CLR, respectively) within each hemisphere. Additionally, we quantified structural connectivity strength between locomotor hubs and assessed relationships with metrics of FoG. FoG+ patients showed greater functional connectivity between the SMA and bilateral MLR and between the SMA and left CLR compared to both FoG− and controls. Importantly, greater functional connectivity between the SMA and MLR was positively correlated with i) clinical, ii) self-reported and iii) objective ratings of freezing severity in FoG+, potentially reflecting a maladaptive neural compensation. The current findings demonstrate a re-organization of functional communication within the locomotor network in FoG+ patients whereby the higher-order motor cortex (SMA) responsible for gait initiation communicates with the MLR and CLR to a greater extent than in FoG− patients and controls. The observed pattern of altered connectivity in FoG+ may indicate a failed attempt by the CNS to compensate for the loss of connectivity between the STN and SMA and may reflect a loss

  4. A Silent Synapse-based Mechanism for Cocaine-induced Locomotor Sensitization

    PubMed Central

    Brown, Travis E.; Lee, Brian R.; Mu, Ping; Ferguson, Deveroux; Dietz, David; Ohnishi, Yoshinori N.; Lin, Ying; Suska, Anna; Ishikawa, Masago; Huang, Yanhua H.; Shen, Haowei; Kalivas, Peter W; Sorg, Barbara A.; Zukin, R. Suzanne; Nestler, Eric; Dong, Yan; Schlüter, Oliver M.

    2011-01-01

    Locomotor sensitization is a common and robust behavioral alteration in rodents whereby following exposure to abused drugs such as cocaine, the animal becomes significantly more hyperactive in response to an acute drug challenge. Here, we further analyzed the role of cocaine-induced silent synapses in the nucleus accumbens (NAc) shell and their contribution to the development of locomotor sensitization. Using a combination of viral vector-mediated genetic manipulations, biochemistry and electrophysiology in a locomotor sensitization paradigm with repeated, daily noncontingent cocaine (15 mg/kg) injections, we show that dominant negative cAMP-element binding protein (CREB) prevents cocaine-induced generation of silent synapses of young (30 d) rats, whereas constitutively active CREB is sufficient to increase the number of NR2B-containing NMDA receptors (NMDAR) at synapses and to generate silent synapses. We further show that occupancy of CREB at the NR2B promoter increases and is causally related to the increase in synaptic NR2B levels. Blockade of NR2B-containing NMDARs by administration of the NR2B-selective antagonist Ro256981 directly into the NAc, under conditions that inhibit cocaine-induced silent synapses, prevents the development of cocaine-elicited locomotor sensitization. Our data are consistent with a cellular cascade whereby cocaine-induced activation of CREB promotes CREB-dependent transcription of NR2B and synaptic incorporation of NR2B-containing NMDARs, which generates new silent synapses within the NAc. We propose that cocaine-induced activation of CREB and generation of new silent synapses may serve as key cellular events mediating cocaine-induced locomotor sensitization. These findings provide a novel cellular mechanism that may contribute to cocaine-induced behavioral alterations. PMID:21632938

  5. Locomotor training: experiencing the changing body.

    PubMed

    Hannold, Elizabeth M; Young, Mary Ellen; Rittman, Maude R; Bowden, Mark G; Behrman, Andrea L

    2006-01-01

    This study examined the experiences of persons with incomplete spinal cord injury who participated in loco-motor training (LT). LT is an emerging rehabilitation intervention for enhancing the recovery of walking in persons with central nervous system disorders. Multiple interviews and field observations provided data from eight participants, including four veterans. Findings indicate that experiences of bodily changes were prevalent among participants. Themes included (1) experiencing impaired or absent proprioception, (2) struggling for bodily control, and (3) experiencing emergent bodily sensations. Themes 1 and 2 reflected bodily disruption as a result of spinal cord injury and were challenging to participants as they attempted to reconnect the body and self through LT. Theme 3 reflected bodily sensations (burning, soreness) that were seen as positive signs of recovery and resulted in hope and motivation. Understanding how LT participants experience bodily changes may enable therapists to develop improved participant-centered intervention approaches.

  6. Nucleus accumbens cocaine-amphetamine regulated transcript mediates food intake during novelty conflict.

    PubMed

    Burghardt, P R; Krolewski, D M; Dykhuis, K E; Ching, J; Pinawin, A M; Britton, S L; Koch, L G; Watson, S J; Akil, H

    2016-05-01

    Obesity is a persistent and pervasive problem, particularly in industrialized nations. It has come to be appreciated that the metabolic health of an individual can influence brain function and subsequent behavioral patterns. To examine the relationship between metabolic phenotype and central systems that regulate behavior, we tested rats with divergent metabolic phenotypes (Low Capacity Runner: LCR vs. High Capacity Runner: HCR) for behavioral responses to the conflict between hunger and environmental novelty using the novelty suppressed feeding (NSF) paradigm. Additionally, we measured expression of mRNA, for peptides involved in energy management, in response to fasting. Following a 24-h fast, LCR rats showed lower latencies to begin eating in a novel environment compared to HCR rats. A 48-h fast equilibrated the latency to begin eating in the novel environment. A 24-h fast differentially affected expression of cocaine-amphetamine regulated transcript (CART) mRNA in the nucleus accumbens (NAc), where 24-h of fasting reduced CART mRNA in LCR rats. Bilateral microinjections of CART 55-102 peptide into the NAc increased the latency to begin eating in the NSF paradigm following a 24-h fast in LCR rats. These results indicate that metabolic phenotype influences how animals cope with the conflict between hunger and novelty, and that these differences are at least partially mediated by CART signaling in the NAc. For individuals with poor metabolic health who have to navigate food-rich and stressful environments, changes in central systems that mediate conflicting drives may feed into the rates of obesity and exacerbate the difficulty individuals have in maintaining weight loss.

  7. Nucleus accumbens cocaine-amphetamine regulated transcript mediates food intake during novelty conflict

    PubMed Central

    Burghardt, PR; Krolewski, DM; Dykhuis, KE; Ching, J; Pinawin, AM; Britton, SL; Koch, LG; Watson, SJ; Akil, H.

    2016-01-01

    Obesity is a persistent and pervasive problem, particularly in industrialized nations. It has come to be appreciated that the metabolic health of an individual can influence brain function and subsequent behavioral patterns. To examine the relationship between metabolic phenotype and central systems that regulate behavior, we tested rats with divergent metabolic phenotypes (Low Capacity Runner: LCR vs. High Capacity Runner: HCR) for behavioral responses to the conflict between hunger and environmental novelty using the novelty suppressed feeding (NSF) paradigm. Additionally, we measured expression of mRNA, for peptides involved in energy management, in response to fasting. Following a 24-h fast, LCR rats showed lower latencies to begin eating in a novel environment compared to HCR rats. A 48-h fast equilibrated the latency to begin eating in the novel environment. A 24-h fast differentially affected expression of cocaine-amphetamine regulated transcript (CART) mRNA in the nucleus accumbens (NAc), where 24-h of fasting reduced CART mRNA in LCR rats. Bilateral microinjections of CART 55–102 peptide into the NAc increased the latency to begin eating in the NSF paradigm following a 24-h fast in LCR rats. These results indicate that metabolic phenotype influences how animals cope with the conflict between hunger and novelty, and that these differences are at least partially mediated by CART signaling in the NAc. For individuals with poor metabolic health who have to navigate food-rich and stressful environments, changes in central systems that mediate conflicting drives may feed into the rates of obesity and exacerbate the difficulty individuals have in maintaining weight loss. PMID:26926827

  8. Something Old, Something New: A Developmental Transition from Familiarity to Novelty Preferences with Hidden Objects

    ERIC Educational Resources Information Center

    Shinskey, Jeanne L.; Munakata, Yuko

    2010-01-01

    Novelty seeking is viewed as adaptive, and novelty preferences in infancy predict cognitive performance into adulthood. Yet 7-month-olds prefer familiar stimuli to novel ones when searching for hidden objects, in contrast to their strong novelty preferences with visible objects (Shinskey & Munakata, 2005). According to a graded representations…

  9. Chronic treatment with curcumin enhances methamphetamine locomotor sensitization and cue-induced reinstatement of methamphetamine self-administration.

    PubMed

    Zhao, Chun; Lou, Zhongze; Zimmer, Benjamin; Yu, Zhewei; Li, Pengping; Ma, Baomiao; Sun, Yan; Huang, Kunyu; Zhou, Wenhua; Liu, Yu

    2012-10-01

    Curcumin, a major active component of Curcuma longa, possesses antidepressant effects that are mediated by the 5-HT system. However, little is known about the effect of curcumin on the behavioral consequences of methamphetamine (METH). The subjects were male, adult Sprague-Dawley rats. In Experiment 1, the effects of 20 and 40 mg/kg curcumin (i.p.) on response rates and breakpoints of 0.06 mg/kg/infusion METH were evaluated. In Experiment 2, rats were self-administering METH for 10 days followed by a 14-day abstinence period. During the abstinence period, the animals were treated with DMSO, 20 or 40 mg/kg curcumin. All rats were then tested for extinction responding and cue-induced reinstatement. In Experiment 3, rats were treated with DMSO, 20, or 40 mg/kg curcumin 15 min before a METH-induced locomotor activity test for 14 consecutive days. In Experiment 4, rats were pretreated with DMSO or curcumin (20 mg/kg or 40 mg/kg) for 13 days and were subsequently tested for METH-induced locomotor activity on the 14th day. In Experiment 5, three groups were tested for locomotor activity after an injection of DMSO, 20, or 40 mg/kg curcumin. The test was repeated for 14 days. Curcumin produced little effect on response rates and breakpoints maintained by METH. Chronic treatment of only 40 mg/kg curcumin during the abstinence phase enhanced cue-induced reinstatement of METH self-administration. Chronic administration of curcumin increased METH-induced sensitization of locomotor activity at the lower (20 mg/kg) but not higher (40 mg/kg) dose. However pretreatment of curcumin alone showed no significant effect on acute locomotor responses to METH and locomotor responses per se. Curcumin enhanced, rather than inhibited the behavioral effects of METH. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Auditory event-related potentials and alpha oscillations in the psychosis prodrome: Neuronal generator patterns during a novelty oddball task

    PubMed Central

    Kayser, Jürgen; Tenke, Craig E.; Kroppmann, Christopher J.; Alschuler, Daniel M.; Fekri, Shiva; Ben-David, Shelly; Corcoran, Cheryl M.; Bruder, Gerard E.

    2014-01-01

    Prior research suggests that event-related potentials (ERP) obtained during active and passive auditory paradigms, which have demonstrated abnormal neurocognitive function in schizophrenia, may provide helpful tools in predicting transition to psychosis. In addition to ERP measures, reduced modulations of EEG alpha, reflecting top-down control required to inhibit irrelevant information, have revealed attentional deficits in schizophrenia and its prodromal stage. Employing a three-stimulus novelty oddball task, nose-referenced 48-channel ERPs were recorded from 22 clinical high-risk (CHR) patients and 20 healthy controls detecting target tones (12% probability, 500 Hz; button press) among nontargets (76%, 350 Hz) and novel sounds (12%). After current source density (CSD) transformation of EEG epochs (−200 to 1000 ms), event-related spectral perturbations were obtained for each site up to 30 Hz and 800 ms after stimulus onset, and simplified by unrestricted time-frequency (TF) principal components analysis (PCA). Alpha event-related desynchronization (ERD) as measured by TF factor 610–9 (spectral peak latency at 610 ms and 9 Hz; 31.9% variance) was prominent over right posterior regions for targets, and markedly reduced in CHR patients compared to controls, particularly in three patients who later developed psychosis. In contrast, low-frequency event-related synchronization (ERS) distinctly linked to novels (260–1; 16.0%; mid-frontal) and N1 sink across conditions (130–1; 3.4%; centro-temporoparietal) did not differ between groups. Analogous time-domain CSD-ERP measures (temporal PCA), consisting of N1 sink, novelty mismatch negativity (MMN), novelty vertex source, novelty P3, P3b, and frontal response negativity, were robust and closely comparable between groups. Novelty MMN at FCz was, however, absent in the three converters. In agreement with prior findings, alpha ERD and MMN may hold particular promise for predicting transition to psychosis among CHR

  11. Semi-Supervised Eigenbasis Novelty Detection

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.; Thompson, David R.

    2013-01-01

    Recent discoveries in high-time-resolution radio astronomy data have focused attention on a new class of events. Fast transients are rare pulses of radio frequency energy lasting from microseconds to seconds that might be produced by a variety of exotic astrophysical phenomena. For example, X-ray bursts, neutron stars, and active galactic nuclei are all possible sources of short-duration, transient radio signals. It is difficult to anticipate where such signals might appear, and they are most commonly discovered through analysis of high-time- resolution data that had been collected for other purposes. Transients are often faint and difficult to detect, so improved detection algorithms can directly benefit the science yield of all such commensal monitoring. A new detection algorithm learns a low-dimensional linear manifold for describing the normal data. High reconstruction error indicates a novel signal that does not match the patterns of normal data. One unsupervised portion of the manifold model adapts its representation in response to recent data. A second supervised portion of the model is made of a basis trained in advance using labeled examples of RFI; this prevents false positives due to these events. For a linear model, an orthonormalization operation is used to combine these bases prior to the anomaly detection decision. Another novel aspect of the approach lies in combining basis vectors learned in an unsupervised, online fashion from the data stream with supervised basis vectors learned in advance from known examples of false alarms. Adaptive, data-driven detection is achieved that is also informed by existing domain knowledge about signals that may be statistically anomalous, but are not interesting and should therefore be ignored. The method was evaluated using data from the Parkes Multibeam Survey. This data set was originally collected to search for pulsars, which are astronomical sources that emit radio pulses at regular periods. However, several

  12. Locomotor Profiling from Rodents to the Clinic and Back Again.

    PubMed

    Young, Jared W; Minassian, Arpi; Geyer, Mark A

    The quantification of unconditioned motoric activity is one of the oldest and most commonly utilized tools in behavioral studies. Although typically measured in reference to psychiatric disorders, e.g., amphetamine-induced hyperactivity used as a model of schizophrenia, bipolar disorder (BD), and Tourette's syndrome, the motoric behavior of psychiatric patients had not been quantified similarly to rodents until recently. The rodent behavioral pattern monitor (BPM) was reverse-translated for use in humans, providing the quantification of not only motoric activity but also the locomotor exploratory profile of various psychiatric populations. This measurement includes the quantification of specific exploration and locomotor patterns. As an example, patients with BD, schizophrenia, and those with history of methamphetamine dependence exhibited unique locomotor profiles. It was subsequently determined that reducing dopamine transporter function selectively recreated the locomotor profile of BD mania patients and not any other patient population. Hence, multivariate locomotor profiling offers a first-step approach toward understanding the neural mechanism(s) underlying abnormal behavior in patients with psychiatric disorders. Advances in wearable technology will undoubtedly enable similar multivariate assessments of exploratory and locomotor behavior in "real-world" contexts. Furthermore, trans-diagnostic studies of locomotor activity profiles will inform about essential brain-based functions that cut across diagnostic nosologies.

  13. What’s New? Children Prefer Novelty in Referent Selection

    PubMed Central

    Horst, Jessica S.; Samuelson, Larissa K.; Kucker, Sarah C.; McMurray, Bob

    2010-01-01

    Determining the referent of a novel name is a critical task for young language learners. The majority of studies on children’s referent selection focus on manipulating the sources of information (linguistic, contextual and pragmatic) that children can use to solve the referent mapping problem. Here, we take a step back and explore how children’s endogenous biases towards novelty and their own familiarity with novel objects influence their performance in such a task. We familiarized 2-year-old children with previously novel objects. Then, on novel name referent selection trials children were asked to select the referent from three novel objects: two previously seen and one completely novel object. Children demonstrated a clear bias to select the most novel object. A second experiment controls for pragmatic responding and replicates this finding. We conclude, therefore, that children’s referent selection is biased by previous exposure and children’s endogenous bias to novelty. PMID:21092945

  14. NOVELTY DETECTION USING AUTO-ASSOCIATIVE NEURAL NETWORK

    SciTech Connect

    H. SOHN; K. WORDEN; C. FARRAR

    2001-05-01

    The primary objective of novelty detection is to examine if a system significantly deviates from the initial baseline condition of the system. In reality, the system is often subject to changing environmental and operation conditions affecting its dynamic characteristics. Such variations include changes in loading, boundary conditions, temperature, and humidity. Most damage diagnosis techniques, however, generally neglect the effects of these changing ambient conditions. Here, a novelty detection technique is developed explicitly taking into account these natural variations of the system in order to minimize false positive indications of true system changes. Auto-associative neural networks are employed to discriminate system changes of interest such as structural deterioration and damage from the natural variations of the system.

  15. Effects of neonatal and adolescent neuroactive steroid manipulation on locomotor activity induced by ethanol in male wistar rats.

    PubMed

    Bartolomé, Iris; Llidó, Anna; Darbra, Sònia; Pallarès, Marc

    2017-07-14

    Neonatal neuroactive steroids levels are crucial for brain development. Alterations of neonatal neuroactive steroids levels induce anxiolytic-like effects and improve exploration in novel environments in adulthood. These behavioural traits, i.e. sensation/novelty seeking, anxiety or impulsivity, are associated with vulnerability to drug use and abuse. Adolescence is also recognized as a particularly critical developmental phase to contribute to vulnerable phenotype. However, the influence of neuroactive steroids during development in the vulnerability to drug addiction has been poorly studied. The aim of the present experiment is to study the effect of early neonatal and adolescent manipulations of neuroactive steroids on the sensitivity to the stimulant effects of ethanol in adult male rats. Therefore, allopregnanolone or finasteride, an allopregnanolone synthesis inhibitor, were injected from postnatal day 5-9. In early adolescence, half of the subjects were injected with progesterone, the main allopregnanolone precursor, and the elevated plus-maze anxiety test was performed. Results indicated that early adolescent progesterone induced anxiolytic-like effects (increase in the percentage of entries and time in open arms). Neonatal finasteride administration decreased locomotor activity induced by ethanol in adolescent vehicle subjects. Interestingly, differences induced by neonatal treatments were not present in the animals that received progesterone in the early adolescence. In conclusion, neuroactive steroid manipulations in crucial stages of development could be playing an important role in behavioural effects of alcohol such as the sensitivity to locomotor stimulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Ethanol-induced Locomotor Sensitization in DBA/2J Mice is Associated with Alterations in GABAA Subunit Gene Expression and Behavioral Sensitivity to GABAA Acting Drugs

    PubMed Central

    Linsenbardt, David N.; Boehm, Stephen L.

    2013-01-01

    Repeated exposure to ethanol may produce increased sensitivity to its acute locomotor stimulant actions, a process referred to as locomotor sensitization. Neuroadaptation within certain brain circuits, including those possessing GABAA receptors, may underlie locomotor sensitization to ethanol. Indeed, GABAA receptors are documented mediators of ethanol's cellular and behavioral actions. Moreover, because subunit composition of this receptor is predictive of its pharmacology, it is possible that alterations in subunit composition contribute to the expression of locomotor sensitization to ethanol. The goal of the present study was to determine if alterations in GABAA subunit composition are associated with the expression of locomotor sensitization in DBA/2J mice, a strain known to be particularly susceptible to the development of this behavioral phenomenon. Following a modified 14 day sensitization procedure (Phillips et al., 1994) relative changes in GABAA subunit gene expression were assessed in discrete mesolimbic brain regions. To determine if the observed changes in gene expression produced functional changes in the locomotor responses to drugs known to either preferentially or generally activate GABAA receptors normally possessing the significantly altered subunits, separate cohorts of animals were challenged with one of several low doses of zolpidem (α1-selective), etomidate (β2/3-selective), or flurazepam (γ2-directed) and assessed for locomotor alterations. Sensitized animals displayed increased expression of the α1, β2, and γ2 (v1) subunits in the Nucleus Accumbens (NAc) but not Ventral Tegmental Area (VTA). Additionally, sensitized animals displayed altered sensitivity to the locomotor actions of etomidate and flurazepam. These results support the hypothesis that neuroadaptive changes in GABAA subunit composition participate in the expression of locomotor sensitization. PMID:20219525

  17. An Investigation of the Effects of Maternal Separation and Novelty on Central Mechanisms Mediating Pituitary-Adrenal Activity in Infant Guinea Pigs (Cavia porcellus)

    PubMed Central

    Maken, Deborah S.; Weinberg, Joanne; Cool, David R.; Hennessy, Michael B.

    2016-01-01

    In mammalian species in which the young exhibit a strong filial attachment (e.g., monkeys, guinea pigs), numerous studies have shown that even brief separation from the attachment figure potently elevates circulating concentrations of glucocorticoids and adrenocorticotropic hormone (ACTH). However, effects of separation on central regulation of this stress response are not known. Therefore, we investigated central mechanisms mediating pituitary-adrenal activation during maternal separation and novelty exposure in guinea pig (Cavia porcellus) pups. Corticotropin-releasing factor (CRF) mRNA expression in the hypothalamic paraventricular nucleus (PVN), and plasma cortisol and ACTH levels, were elevated only during separation in a novel environment. C-Fos activity was elevated in the medial amygdala (MeA) and reduced in the bed nucleus of the stria terminalis (BNST) during novelty exposure, regardless of separation. On the other hand, c-Fos activity was elevated in the PVN during separation, regardless of novelty exposure. These results demonstrate independent and combined effects of separation and novelty in regions of the guinea pig CNS that regulate pituitary-adrenal activity. Moreover, they suggest that a pathway from MeA to BNST to PVN mediates responses to novelty in the guinea pig pup, as in the adult rat, though inputs from other cell populations appear required to fully account for the HPA activity observed here. PMID:21038937

  18. The importance of novelty: male-female interactions among blue-black grassquits in captivity.

    PubMed

    Dias, Raphael I; Oliveira, Rui F; Podos, Jeffrey; Macedo, Regina H

    2014-03-01

    Mate choice is a primary mechanism driving the evolution of sexually selected traits such as elaborate displays and ornaments. In a majority of taxa studied to date, females are seen to actively sample and evaluate multiple males, presumably to optimize mating opportunities. During this process females may encounter males both familiar and novel, a distinction that might influence how mate choice proceeds. Using a socially monogamous passerine, the blue-black grassquit (Volatinia jacarina), we studied how females respond to novel versus familiar ("paired") males, and how encounters with novel males influence subsequent interactions with their paired males. Additionally, we measured the hormonal response of males after visualizing their paired females interacting with novel males. We found that females were attentive to novel males irrespective of these males' phenotypic attributes, suggesting that in these interactions novelty is highly relevant. After exposure to novel males, females tended to respond aggressively towards their paired males; by contrast, the behaviour of males towards their paired females did not change. Moreover, we did not detect any hormonal responses of males to viewing their paired females interacting with novel males. Together these results suggest that the distinction between familiarity and novelty may hold special relevance for females in mate choice, a finding that bears upon our understanding of the evolution of extra-pair paternity and reproductive behaviour.

  19. MMN and novelty P3 in coma and other altered states of consciousness: a review.

    PubMed

    Morlet, Dominique; Fischer, Catherine

    2014-07-01

    In recent decades, there has been a growing interest in the assessment of patients in altered states of consciousness. There is a need for accurate and early prediction of awakening and recovery from coma. Neurophysiological assessment of coma was once restricted to brainstem auditory and primary cortex somatosensory evoked potentials elicited in the 30 ms range, which have both shown good predictive value for poor coma outcome only. In this paper, we review how passive auditory oddball paradigms including deviant and novel sounds have proved their efficiency in assessing brain function at a higher level, without requiring the patient's active involvement, thus providing an enhanced tool for the prediction of coma outcome. The presence of an MMN in response to deviant stimuli highlights preserved automatic sensory memory processes. Recorded during coma, MMN has shown high specificity as a predictor of recovery of consciousness. The presence of a novelty P3 in response to the subject's own first name presented as a novel (rare) stimulus has shown a good correlation with coma awakening. There is now a growing interest in the search for markers of consciousness, if there are any, in unresponsive patients (chronic vegetative or minimally conscious states). We discuss the different ERP patterns observed in these patients. The presence of novelty P3, including parietal components and possibly followed by a late parietal positivity, raises the possibility that some awareness processes are at work in these unresponsive patients.

  20. MMN and Novelty P3 in Coma and Other Altered States of Consciousness: A Review

    PubMed Central

    Morlet, Dominique; Fischer, Catherine

    2014-01-01

    In recent decades, there has been a growing interest in the assessment of patients in altered states of consciousness. There is a need for accurate and early prediction of awakening and recovery from coma. Neurophysiological assessment of coma was once restricted to brainstem auditory and primary cortex somatosensory evoked potentials elicited in the thirty millisecond range, which have both shown good predictive value for poor coma outcome only. In this paper, we review how passive auditory oddball paradigms including deviant and novel sounds have proved their efficiency in assessing brain function at a higher level, without requiring the patient’s active involvement, thus providing an enhanced tool for the prediction of coma outcome. The presence of an MMN in response to deviant stimuli highlights preserved automatic sensory memory processes. Recorded during coma, MMN has shown high specificity as a predictor of recovery of consciousness. The presence of a novelty P3 in response to the subject’s own first name presented as a novel (rare) stimulus has shown a good correlation with coma awakening. There is now a growing interest in the search for markers of consciousness, if there are any, in unresponsive patients (chronic vegetative or minimally conscious states). We discuss the different ERP patterns observed in these patients. The presence of novelty P3, including parietal components and possibly followed by a late parietal positivity, raises the possibility that some awareness processes are at work in these unresponsive patients. PMID:24281786

  1. Evidence That GABA Mediates Dopaminergic and Serotonergic Pathways Associated with Locomotor Activity in Juvenile Chinook Salmon (Oncorhynchus tshawytscha)

    USGS Publications Warehouse

    Clements, S.; Schreck, C.B.

    2004-01-01

    The authors examined the control of locomotor activity in juvenile salmon (Oncorhynchus tshawytscha) by manipulating 3 neurotransmitter systems-gamma-amino-n-butyric acid (GABA), dopamine, and serotonin-as well as the neuropeptide corticotropin releasing hormone (CRH). Intracerebroventricular (ICV) injections of CRH and the GABAAagonist muscimol stimulated locomotor activity. The effect of muscimol was attenuated by administration of a dopamine receptor antagonist, haloperidol. Conversely, the administration of a dopamine uptake inhibitor (4???,4??? -difluoro-3-alpha-[diphenylmethoxy] tropane hydrochloride [DUI]) potentiated the effect of muscimol. They found no evidence that CRH-induced hyperactivity is mediated by dopaminergic systems following concurrent injections of haloperidol or DUI with CRH. Administration of muscimol either had no effect or attenuated the locomotor response to concurrent injections of CRH and fluoxetine, whereas the GABAA antagonist bicuculline methiodide potentiated the effect of CRH and fluoxetine.

  2. Environmental novelty is associated with a selective increase in Fos expression in the output elements of the hippocampal formation and the perirhinal cortex.

    PubMed

    VanElzakker, Michael; Fevurly, Rebecca D; Breindel, Tressa; Spencer, Robert L

    2008-12-01

    If the hippocampus plays a role in the detection of novel environmental features, then novelty should be associated with altered hippocampal neural activity and perhaps also measures of neuroplasticity. We examined Fos protein expression within subregions of rat hippocampal formation as an indicator of recent increases in neuronal excitation and cellular processes that support neuroplasticity. Environmental novelty, but not environmental complexity, led to a selective increase of Fos induction in the final "output" subregion of the dorsal hippocampal trisynaptic circuit (CA1) and a primary projection site (layer five of the lateral entorhinal cortex, ERC), as well as in the perirhinal cortex. There was no selective effect of novelty on Fos expression within "input" elements of the trisynaptic circuit (ERC layer two, the dentate gyrus or CA3) or other comparison brain regions that may be responsive to overall motor-sensory activity or anxiety levels (primary somatosensory and motor cortex or hypothalamic paraventricular nucleus). Test session ambulatory behavior increased with both novelty and environmental complexity and was not significantly correlated with Fos expression patterns in any of the brain regions examined. In contrast, the extent of manipulated environmental novelty was strongly correlated with Fos expression in CA1. These results support the prospect that a novelty-associated signal is generated within hippocampal neurocircuitry, is relayed to cortical projection sites, and specifically up-regulates neuroplasticity-supporting processes with dorsal hippocampal CA1 and ERC layer five. Whether novelty-dependent Fos induction in perirhinal cortex depends on this hippocampal output or reflects an independent process remains to be determined.

  3. Evidence for a Role of Orexin/Hypocretin System in Vestibular Lesion-Induced Locomotor Abnormalities in Rats

    PubMed Central

    Pan, Leilei; Qi, Ruirui; Wang, Junqin; Zhou, Wei; Liu, Jiluo; Cai, Yiling

    2016-01-01

    Vestibular damage can induce locomotor abnormalities in both animals and humans. Rodents with bilateral vestibular loss showed vestibular deficits syndrome such as circling, opisthotonus as well as locomotor and exploratory hyperactivity. Previous studies have investigated the changes in the dopamine system after vestibular loss, but the results are inconsistent and inconclusive. Numerous evidences indicate that the orexin system is implicated in central motor control. We hypothesized that orexin may be potentially involved in vestibular loss-induced motor disorders. In this study, we examined the effects of arsanilate- or 3,3′-iminodipropionitrile (IDPN)-induced vestibular lesion (AVL or IVL) on the orexin-A (OXA) labeling in rat hypothalamus using immunohistochemistry. The vestibular lesion-induced locomotor abnormalities were recorded and verified using a histamine H4 receptor antagonist JNJ7777120 (20 mg/kg, i.p.). The effects of the orexin receptor type 1 antagonist SB334867 (16 μg, i.c.v.) on these behavior responses were also investigated. At 72 h post-AVL and IVL, animals exhibited vestibular deficit syndrome and locomotor hyperactivity in the home cages. These responses were significantly alleviated by JNJ7777120 which also eliminated AVL-induced increases in exploratory behavior in an open field. The numbers of OXA-labeled neurons in the hypothalamus were significantly increased in the AVL animals at 72 h post-AVL and in the IVL animals at 24, 48, and 72 h post-IVL. SB334867 significantly attenuated the vestibular deficit syndrome and locomotor hyperactivity at 72 h post-AVL and IVL. It also decreased exploratory behavior in the AVL animals. These results suggested that the alteration of OXA expression might contribute to locomotor abnormalities after acute vestibular lesion. The orexin receptors might be the potential therapeutic targets for vestibular disorders. PMID:27507932

  4. Insulin-Dependent Activation of MCH Neurons Impairs Locomotor Activity and Insulin Sensitivity in Obesity.

    PubMed

    Hausen, A Christine; Ruud, Johan; Jiang, Hong; Hess, Simon; Varbanov, Hristo; Kloppenburg, Peter; Brüning, Jens C

    2016-12-06

    Melanin-concentrating-hormone (MCH)-expressing neurons (MCH neurons) in the lateral hypothalamus (LH) are critical regulators of energy and glucose homeostasis. Here, we demonstrate that insulin increases the excitability of these neurons in control mice. In vivo, insulin promotes phosphatidylinositol 3-kinase (PI3K) signaling in MCH neurons, and cell-type-specific deletion of the insulin receptor (IR) abrogates this response. While lean mice lacking the IR in MCH neurons (IR(ΔMCH)) exhibit no detectable metabolic phenotype under normal diet feeding, they present with improved locomotor activity and insulin sensitivity under high-fat-diet-fed, obese conditions. Similarly, obesity promotes PI3 kinase signaling in these neurons, and this response is abrogated in IR(ΔMCH) mice. In turn, acute chemogenetic activation of MCH neurons impairs locomotor activity but not insulin sensitivity. Collectively, our experiments reveal an insulin-dependent activation of MCH neurons in obesity, which contributes via distinct mechanisms to the manifestation of impaired locomotor activity and insulin resistance.

  5. Spinocerebellar ataxia type 13 mutant potassium channel alters neuronal excitability and causes locomotor deficits in zebrafish.

    PubMed

    Issa, Fadi A; Mazzochi, Christopher; Mock, Allan F; Papazian, Diane M

    2011-05-04

    Whether changes in neuronal excitability can cause neurodegenerative disease in the absence of other factors such as protein aggregation is unknown. Mutations in the Kv3.3 voltage-gated K(+) channel cause spinocerebellar ataxia type 13 (SCA13), a human autosomal-dominant disease characterized by locomotor impairment and the death of cerebellar neurons. Kv3.3 channels facilitate repetitive, high-frequency firing of action potentials, suggesting that pathogenesis in SCA13 is triggered by changes in electrical activity in neurons. To investigate whether SCA13 mutations alter excitability in vivo, we expressed the human dominant-negative R420H mutant subunit in zebrafish. The disease-causing mutation specifically suppressed the excitability of Kv3.3-expressing, fast-spiking motor neurons during evoked firing and fictive swimming and, in parallel, decreased the precision and amplitude of the startle response. The dominant-negative effect of the mutant subunit on K(+) current amplitude was directly responsible for the reduced excitability and locomotor phenotype. Our data provide strong evidence that changes in excitability initiate pathogenesis in SCA13 and establish zebrafish as an excellent model system for investigating how changes in neuronal activity impair locomotor control and cause cell death.

  6. Dynamic Locomotor Capabilities Revealed by Early Dinosaur Trackmakers from Southern Africa

    PubMed Central

    Wilson, Jeffrey A.; Marsicano, Claudia A.; Smith, Roger M. H.

    2009-01-01

    Background A new investigation of the sedimentology and ichnology of the Early Jurassic Moyeni tracksite in Lesotho, southern Africa has yielded new insights into the behavior and locomotor dynamics of early dinosaurs. Methodology/Principal Findings The tracksite is an ancient point bar preserving a heterogeneous substrate of varied consistency and inclination that includes a ripple-marked riverbed, a bar slope, and a stable algal-matted bar top surface. Several basal ornithischian dinosaurs and a single theropod dinosaur crossed its surface within days or perhaps weeks of one another, but responded to substrate heterogeneity differently. Whereas the theropod trackmaker accommodated sloping and slippery surfaces by gripping the substrate with its pedal claws, the basal ornithischian trackmakers adjusted to the terrain by changing between quadrupedal and bipedal stance, wide and narrow gauge limb support (abduction range = 31°), and plantigrade and digitigrade foot posture. Conclusions/Significance The locomotor adjustments coincide with changes in substrate consistency along the trackway and appear to reflect ‘real time’ responses to a complex terrain. It is proposed that these responses foreshadow important locomotor transformations characterizing the later evolution of the two main dinosaur lineages. Ornithischians, which shifted from bipedal to quadrupedal posture at least three times in their evolutionary history, are shown to have been capable of adopting both postures early in their evolutionary history. The substrate-gripping behavior demonstrated by the early theropod, in turn, is consistent with the hypothesized function of pedal claws in bird ancestors. PMID:19806213

  7. Locomotor training alters the behavior of flexor reflexes during walking in human spinal cord injury.

    PubMed

    Smith, Andrew C; Mummidisetty, Chaithanya K; Rymer, William Zev; Knikou, Maria

    2014-11-01

    In humans, a chronic spinal cord injury (SCI) impairs the excitability of pathways mediating early flexor reflexes and increases the excitability of late, long-lasting flexor reflexes. We hypothesized that in individuals with SCI, locomotor training will alter the behavior of these spinally mediated reflexes. Nine individuals who had either chronic clinically motor complete or incomplete SCI received an average of 44 locomotor training sessions. Flexor reflexes, elicited via sural nerve stimulation of the right or left leg, were recorded from the ipsilateral tibialis anterior (TA) muscle before and after body weight support (BWS)-assisted treadmill training. The modulation pattern of the ipsilateral TA responses following innocuous stimulation of the right foot was also recorded in 10 healthy subjects while they stepped at 25% BWS to investigate whether body unloading during walking affects the behavior of these responses. Healthy subjects did not receive treadmill training. We observed a phase-dependent modulation of early TA flexor reflexes in healthy subjects with reduced body weight during walking. The early TA flexor reflexes were increased at heel contact, progressively decreased during the stance phase, and then increased throughout the swing phase. In individuals with SCI, locomotor training induced the reappearance of early TA flexor reflexes and changed the amplitude of late TA flexor reflexes during walking. Both early and late TA flexor reflexes were modulated in a phase-dependent pattern after training. These new findings support the adaptive capability of the injured nervous system to return to a prelesion excitability and integration state.

  8. Influence of temperature on daily locomotor activity in the crab Uca pugilator

    PubMed Central

    Dunster, Gideon P.; Sbragaglia, Valerio; Aguzzi, Jacopo; de la Iglesia, Horacio O.

    2017-01-01

    Animals living in the intertidal zone are exposed to prominent temperature changes. To cope with the energetic demands of environmental thermal challenges, ectotherms rely mainly on behavioral responses, which may change depending on the time of the day and seasonally. Here, we analyze how temperature shapes crabs’ behavior at 2 different times of the year and show that a transition from constant cold (13.5°C) to constant warm (17.5°C) water temperature leads to increased locomotor activity levels throughout the day in fiddler crabs (Uca pugilator) collected during the summer. In contrast, the same transition in environmental temperature leads to a decrease in the amplitude of the daily locomotor activity rhythm in crabs collected during the winter. In other words, colder temperatures during the cold season favor a more prominent diurnal behavior. We interpret this winter-summer difference in the response of daily locomotor activity to temperature changes within the framework of the circadian thermoenergetics hypothesis, which predicts that a less favorable energetic balance would promote a more diurnal activity pattern. During the winter, when the energetic balance is likely less favorable, crabs would save energy by being more active during the expected high-temperature phase of the day—light phase—and less during the expected low-temperature phase of the day—dark phase. Our results suggest that endogenous rhythms in intertidal ectotherms generate adaptive behavioral programs to cope with thermoregulatory demands of the intertidal habitat. PMID:28445533

  9. Influence of temperature on daily locomotor activity in the crab Uca pugilator.

    PubMed

    Mat, Audrey M; Dunster, Gideon P; Sbragaglia, Valerio; Aguzzi, Jacopo; de la Iglesia, Horacio O

    2017-01-01

    Animals living in the intertidal zone are exposed to prominent temperature changes. To cope with the energetic demands of environmental thermal challenges, ectotherms rely mainly on behavioral responses, which may change depending on the time of the day and seasonally. Here, we analyze how temperature shapes crabs' behavior at 2 different times of the year and show that a transition from constant cold (13.5°C) to constant warm (17.5°C) water temperature leads to increased locomotor activity levels throughout the day in fiddler crabs (Uca pugilator) collected during the summer. In contrast, the same transition in environmental temperature leads to a decrease in the amplitude of the daily locomotor activity rhythm in crabs collected during the winter. In other words, colder temperatures during the cold season favor a more prominent diurnal behavior. We interpret this winter-summer difference in the response of daily locomotor activity to temperature changes within the framework of the circadian thermoenergetics hypothesis, which predicts that a less favorable energetic balance would promote a more diurnal activity pattern. During the winter, when the energetic balance is likely less favorable, crabs would save energy by being more active during the expected high-temperature phase of the day-light phase-and less during the expected low-temperature phase of the day-dark phase. Our results suggest that endogenous rhythms in intertidal ectotherms generate adaptive behavioral programs to cope with thermoregulatory demands of the intertidal habitat.

  10. Dynamic locomotor capabilities revealed by early dinosaur trackmakers from southern Africa.

    PubMed

    Wilson, Jeffrey A; Marsicano, Claudia A; Smith, Roger M H

    2009-10-06

    A new investigation of the sedimentology and ichnology of the Early Jurassic Moyeni tracksite in Lesotho, southern Africa has yielded new insights into the behavior and locomotor dynamics of early dinosaurs. The tracksite is an ancient point bar preserving a heterogeneous substrate of varied consistency and inclination that includes a ripple-marked riverbed, a bar slope, and a stable algal-matted bar top surface. Several basal ornithischian dinosaurs and a single theropod dinosaur crossed its surface within days or perhaps weeks of one another, but responded to substrate heterogeneity differently. Whereas the theropod trackmaker accommodated sloping and slippery surfaces by gripping the substrate with its pedal claws, the basal ornithischian trackmakers adjusted to the terrain by changing between quadrupedal and bipedal stance, wide and narrow gauge limb support (abduction range = 31 degrees ), and plantigrade and digitigrade foot posture. The locomotor adjustments coincide with changes in substrate consistency along the trackway and appear to reflect 'real time' responses to a complex terrain. It is proposed that these responses foreshadow important locomotor transformations characterizing the later evolution of the two main dinosaur lineages. Ornithischians, which shifted from bipedal to quadrupedal posture at least three times in their evolutionary history, are shown to have been capable of adopting both postures early in their evolutionary history. The substrate-gripping behavior demonstrated by the early theropod, in turn, is consistent with the hypothesized function of pedal claws in bird ancestors.

  11. Reliability review of the remote tool delivery system locomotor

    SciTech Connect

    Chesser, J.B.

    1999-04-01

    The locomotor being built by RedZone Robotics is designed to serve as a remote tool delivery (RID) system for waste retrieval, tank cleaning, viewing, and inspection inside the high-level waste tanks 8D-1 and 8D-2 at West Valley Nuclear Services (WVNS). The RTD systm is to be deployed through a tank riser. The locomotor portion of the RTD system is designed to be inserted into the tank and is to be capable of moving around the tank by supporting itself and moving on the tank internal structural columns. The locomotor will serve as a mounting platform for a dexterous manipulator arm. The complete RTD system consists of the locomotor, dexterous manipulator arm, cameras, lights, cables, hoses, cable/hose management system, power supply, and operator control station.

  12. The locomotor anatomy of Australopithecus afarensis.

    PubMed

    Stern, J T; Susman, R L

    1983-03-01

    The postcranial skeleton of Australopithecus afarensis from the Hadar Formation, Ethiopia, and the footprints from the Laetoli Beds of northern Tanzania, are analyzed with the goal of determining (1) the extent to which this ancient hominid practiced forms of locomotion other than terrestrial bipedality, and (2) whether or not the terrestrial bipedalism of A. afarensis was notably different from that of modern humans. It is demonstrated that A. afarensis possessed anatomic characteristics that indicate a significant adaptation for movement in the trees. Other structural features point to a mode of terrestrial bipedality that involved less extension at the hip and knee than occurs in modern humans, and only limited transfer of weight onto the medial part of the ball of the foot, but such conclusions remain more tentative than that asserting substantive arboreality. A comparison of the specimens representing smaller individuals, presumably female, to those of larger individuals, presumably male, suggests sexual differences in locomotor behavior linked to marked size dimorphism. The males were probably less arboreal and engaged more frequently in terrestrial bipedalism. In our opinion, A. afarensis from Hadar is very close to what can be called a "missing link." We speculate that earlier representatives of the A. afarensis lineage will present not a combination of arboreal and bipedal traits, but rather the anatomy of a generalized ape.

  13. Locomotor sequence learning in visually guided walking.

    PubMed

    Choi, Julia T; Jensen, Peter; Nielsen, Jens Bo

    2016-04-01

    Voluntary limb modifications must be integrated with basic walking patterns during visually guided walking. In this study we tested whether voluntary gait modifications can become more automatic with practice. We challenged walking control by presenting visual stepping targets that instructed subjects to modify step length from one trial to the next. Our sequence learning paradigm is derived from the serial reaction-time (SRT) task that has been used in upper limb studies. Both random and ordered sequences of step lengths were used to measure sequence-specific and sequence-nonspecific learning during walking. In addition, we determined how age (i.e., healthy young adults vs. children) and biomechanical factors (i.e., walking speed) affected the rate and magnitude of locomotor sequence learning. The results showed that healthy young adults (age 24 ± 5 yr,n= 20) could learn a specific sequence of step lengths over 300 training steps. Younger children (age 6-10 yr,n= 8) had lower baseline performance, but their magnitude and rate of sequence learning were the same compared with those of older children (11-16 yr,n= 10) and healthy adults. In addition, learning capacity may be more limited at faster walking speeds. To our knowledge, this is the first study to demonstrate that spatial sequence learning can be integrated with a highly automatic task such as walking. These findings suggest that adults and children use implicit knowledge about the sequence to plan and execute leg movement during visually guided walking.

  14. Locomotor-respiratory coupling during wheelchair propulsion.

    PubMed

    MacDonald, M L; Kirby, R L; Nugent, S T; MacLeod, D A

    1992-04-01

    Visceral movement due to impact loading is believed to play a role in the locomotor-respiratory coupling (LRC) that has been detected in a number of mammalian species. In the bird and bat species in which LRC has been described, the effect of the wing muscles on the timing of respiration appears to be a dominant influence. To test the hypothesis that LRC occurs in humans propelling wheelchairs (where there is no impact loading and the arms are used for locomotion), we studied 10 wheelchair athletes on a motorized treadmill at three speeds. Each subject's data were analyzed by spectral analysis (based on the fast Fourier transform), which detected apparent LRC (rates within 1% of a single-digit integer ratio) in 12 (40%) of the 30 test settings. However, a control analysis, in which each subject's arm-thrust rates were compared with another subject's breathing rates, revealed apparent (but false) coupling in 8 (27%), not significantly less often (using the chi 2 test). These findings appear to refute the hypothesis that LRC occurs during wheelchair propulsion. These data are consistent with the theory that the visceral piston is important to LRC and suggest that rhythmic arm movements are insufficient to induce the phenomenon in this setting.

  15. Locomotor requirements for bipedal locomotion: a Delphi survey.

    PubMed

    Hedman, Lois Deming; Morris, David M; Graham, Cecilia L; Brown, Cynthia J; Ford, Matthew P; Ingram, Debbie A; Hilliard, Marjorie J; Salzman, Alice J

    2014-01-01

    Bipedal locomotor control requirements may be useful as classifications for walking dysfunction because they go beyond gait analysis to address all issues contributing to walking dysfunction. The objective of this study was to determine whether locomotor experts could achieve consensus about the requirements for bipedal locomotion. Locomotor experts from physical therapy and other related professions participated in an electronic mail Delphi survey. Experts recommended additions, deletions, rewording, and merges for 15 proposed locomotor requirements in round 1. In rounds 2 and 3, panelists commented on and rated the validity, mutual exclusiveness, and understandability of each requirement. Consensus was defined a priori as: (1) 75% or more panelists agree or strongly agree that a requirement is valid, mutually exclusive, and understandable in round 3; (2) no difference between round 2 and 3 ratings with kappa coefficients ≥.60; and (3) a reduction in panelists who commented and convergence of comments between rounds 1 and 3. Content analysis and nonparametric statistics were used. Fifty-eight panelists reached full consensus on 5 locomotor requirements (Initiation, Termination, Anticipatory Dynamic Balance, Multi-Task Capacity, and Walking Confidence) and partial consensus for 7 other requirements. There were no significant differences in ratings between rounds 2 and 3, and there was a decrease in the percentage of panelists who commented between rounds 1 and 3. The study's 6-month time frame may have contributed to panelist attrition. Locomotor experts achieved consensus on several bipedal locomotor requirements. With validation, these requirements can provide the framework for a clinically feasible and systematic diagnostic tool for physical therapists to categorize locomotor problems and standardize intervention for walking dysfunction.

  16. Dimensions of integration in interdisciplinary explanations of the origin of evolutionary novelty.

    PubMed

    Love, Alan C; Lugar, Gary L

    2013-12-01

    Many philosophers of biology have embraced a version of pluralism in response to the failure of theory reduction but overlook how concepts, methods, and explanatory resources are in fact coordinated, such as in interdisciplinary research where the aim is to integrate different strands into an articulated whole. This is observable for the origin of evolutionary novelty-a complex problem that requires a synthesis of intellectual resources from different fields to arrive at robust answers to multiple allied questions. It is an apt locus for exploring new dimensions of explanatory integration because it necessitates coordination among historical and experimental disciplines (e.g., geology and molecular biology). These coordination issues are widespread for the origin of novel morphologies observed in the Cambrian Explosion. Despite an explicit commitment to an integrated, interdisciplinary explanation, some potential disciplinary contributors are excluded. Notable among these exclusions is the physics of ontogeny. We argue that two different dimensions of integration-data and standards-have been insufficiently distinguished. This distinction accounts for why physics-based explanatory contributions to the origin of novelty have been resisted: they do not integrate certain types of data and differ in how they conceptualize the standard of uniformitarianism in historical, causal explanations. Our analysis of these different dimensions of integration contributes to the development of more adequate and integrated explanatory frameworks. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Effects of context novelty vs. familiarity on latent inhibition with a conditioned taste aversion procedure.

    PubMed

    Quintero, E; Díaz, E; Vargas, J P; Schmajuk, N; López, J C; De la Casa, L G

    2011-02-01

    The latent inhibition phenomenon is observed when a conditioned stimulus is preexposed without any consequence before conditioning. The result of this manipulation is a reduction in conditioned response intensity to such a stimulus. In this study, we analyse the role of context novelty/familiarity on LI modulation by changing the context using a three-stage conditioned taste aversion procedure. Experiment 1 revealed that, similar to other learning procedures, a context change between preexposure and conditioning/testing (but not between preexposure/conditioning and testing) resulted in LI attenuation when the experimental contexts were novel. Experiment 2, using animals' home cages as one of the contexts, revealed a different pattern of results, with an unexpected increase in LI magnitude when the context change was introduced between conditioning and test stages. The Schmajuk et al. (1996) computational model explains these results in terms of the increased novelty of the conditioned stimulus during preexposure, conditioning, and testing. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Locomotor adaptation and locomotor adaptive learning in Parkinson's disease and normal aging.

    PubMed

    Roemmich, Ryan T; Nocera, Joe R; Stegemöller, Elizabeth L; Hassan, Anhar; Okun, Michael S; Hass, Chris J

    2014-02-01

    Locomotor adaptation enables safe, efficient navigation among changing environments. We investigated how healthy young (HYA) and older (HOA) adults and persons with Parkinson's disease (PD) adapt to walking on a split-belt treadmill, retain adapted gait parameters during re-adaptation, and store aftereffects to conventional treadmill walking. Thirteen PD, fifteen HYA, and fifteen HOA walked on a split-belt treadmill for ten minutes with one leg twice as fast as the other. Participants later re-adapted to the same conditions to assess retention of the split-belt gait pattern. After re-adaptation, we assessed aftereffects of this pattern during conventional treadmill walking. Persons with PD exhibited step length asymmetry throughout many adaptation and adaptive learning conditions. Early adaptation was similar across groups, though HYA and HOA continued to adapt into late adaptation while PD did not. Despite pervasive step length asymmetry among conditions which were symmetric in HYA and HOA, persons with PD demonstrated significant step length aftereffects during conventional treadmill walking after split-belt walking. Though they may exhibit a default asymmetry under various walking conditions, persons with PD can adapt and store new walking patterns. Locomotor adaptation therapy may be effective in ameliorating asymmetric gait deficits in persons with PD. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Furcation and fusion: The phylogenetics of evolutionary novelty.

    PubMed

    Oakley, Todd H

    2017-09-18

    Novelty and innovation are fundamental yet relatively understudied concepts in evolution. We may study the history and provenance of novelty using phylogenetics, where key questions include when evolution occurs by tree-like branching and when it occurs by movement of distantly related parts in processes akin to horizontal transfer. Perfectly vertical inheritance, often an assumption of evolutionary trees, requires simultaneous co-duplication of the parts of a duplicating or speciating (processes I collectively call 'furcating') biological feature. However, simultaneous co-duplication of many parts usually requires variational processes that are rare. Therefore, instead of always being perfectly tree-like, evolution often involves events that incorporate or fuse more distantly related parts into new units during evolution, which herein I call 'fusion'. Exon shuffling, horizontal gene transfer, introgression, and co-option are such fusion processes at different levels of organization. The ubiquity of processes that fuse distantly related parts has wide ranging implications for the study of macroevolution. For one, the central metaphor of a tree of life will often be incomplete, to the point where we may consider a different metaphor, such as economic public goods, or a 'web of life'. Secondly, we often may need to expand commonly used phylogenetic models and methods, highlighting a need for an expansive toolkit for studying evolutionary history. Even though furcation - the splitting and individuation of biological features - does happen, fusion of distant parts may often be just as critical for the evolution of novelties, and must formally be incorporated into the metaphors, models, and visualization of evolutionary history. This will allow us to understand the timing, order of appearance, and diversification rates of developmental systems, including cell types, organs, behavior, and language, which very commonly evolve through co-option. Copyright © 2017

  20. Relationship between ethanol preference and sensation/novelty seeking.

    PubMed

    Manzo, Lidia; Gómez, Ma José; Callejas-Aguilera, José E; Donaire, Rocío; Sabariego, Marta; Fernández-Teruel, Alberto; Cañete, Antoni; Blázquez, Gloria; Papini, Mauricio R; Torres, Carmen

    2014-06-22

    High- and low-avoidance Roman inbred rat strains (RHA-I, RLA-I) were selected for extreme differences in two-way active avoidance. RHA-I rats also express less anxiety than RLA-I rats. This study compared male Roman rats in ethanol preference and sensation/novelty seeking. Rats were first exposed in counterbalanced order to the hole-board test (forced exposure to novelty) and the Y-maze and emergence tests (free choice between novel and familiar locations). Then, rats were tested in 24-h, two-bottle preference tests with water in one bottle and ethanol (2, 4, 6, 8, or 10% in successive days). Compared to RLA-I rats, RHA-I rats showed (1) higher frequency and time in head dipping, (2) higher activity, and (3) lower frequency of rearing and grooming in the hole-board test, and (4) remained in the novel arm longer in the Y-maze test. No strain differences were observed in the emergence test. RHA-I rats exhibited higher preference for and consumed more ethanol than RLA-I rats at all concentrations. However, both strains preferred ethanol over water for 2-4% concentrations, but water over ethanol for 6-10% concentrations. Factorial analysis with all the rats pooled identified a two-factor solution, one grouping preferred ethanol concentrations (2-4%) with head dipping and grooming in the hole board, and another factor grouping the nonpreferred ethanol concentrations (6-10%) with activity in the hole board and novel-arm time in the Y-maze test. These results show that preference for ethanol is associated with different aspects of behavior measured in sensation/novelty-seeking tests.

  1. Attenuated methamphetamine-induced locomotor sensitization in serotonin transporter knockout mice is restored by serotonin 1B receptor antagonist treatment.

    PubMed

    Igari, Moe; Shen, Hao-Wei; Hagino, Yoko; Fukushima, Setsu; Kasahara, Yoshiyuki; Lesch, Klaus-Peter; Murphy, Dennis L; Hall, Frank Scott; Uhl, George R; Ikeda, Kazutaka; Yaegashi, Nobuo; Sora, Ichiro

    2015-02-01

    Repeated administration of methamphetamine (METH) enhances acute locomotor responses to METH administered in the same context, a phenomenon termed as 'locomotor sensitization'. Although many of the acute effects of METH are mediated by its influences on the compartmentalization of dopamine, serotonin systems have also been suggested to influence the behavioral effects of METH in ways that are not fully understood. The present experiments examined serotonergic roles in METH-induced locomotor sensitization by assessing: (a) the effect of serotonin transporter (SERT; Slc6A4) knockout (KO) on METH-induced locomotor sensitization; (b) extracellular monoamine levels in METH-treated animals as determined by in-vivo microdialysis; and (c) effects of serotonin (5-HT) receptor antagonists on METH-induced behavioral sensitization, with focus on effects of the 5-HT1B receptor antagonist SB 216641 and a comparison with the 5-HT2 receptor antagonist ketanserin. Repeated METH administration failed to induce behavioral sensitization in homozygous SERT KO (SERT-/-) mice under conditions that produced substantial sensitization in wild-type or heterozygous SERT KO (SERT+/-) mice. The selective 5-HT1B antagonist receptor SB 216641 restored METH-induced locomotor sensitization in SERT-/- mice, whereas ketanserin was ineffective. METH-induced increases in extracellular 5-HT (5-HTex) levels were substantially reduced in SERT-/- mice, although SERT genotype had no effect on METH-induced increases in extracellular dopamine. These experiments demonstrate that 5-HT actions, including those at 5-HT1B receptors, contribute to METH-induced locomotor sensitization. Modulation of 5-HT1B receptors might aid therapeutic approaches to the sequelae of chronic METH use.

  2. Inbred Lewis and Fischer 344 rat strains differ not only in novelty- and amphetamine-induced behaviors, but also in dopamine transporter activity in vivo

    PubMed Central

    Gulley, Joshua M.; Everett, Carson V.; Zahniser, Nancy R.

    2007-01-01

    Inbred Lewis (LEW) and Fischer 344 (F344) rats are differentially sensitive to drugs of abuse, making them useful for studying addiction-related neural mechanisms. Here, we investigated whether strain differences in dopamine transporters (DATs) in dorsal striatum (dSTR) and/or nucleus accumbens (NAc) may help to explain their behavioral differences. The behavior of male LEW and F344 rats was assessed in an open-field arena during habituation to novelty and after an i.v. infusion of saline and/or 0.5 mg/kg d-amphetamine (AMPH). In vitro measures of DAT binding, protein and cell-surface expression, as well as in vitro and in vivo measures of function, were used to compare DATs in dSTR and NAc of these two strains. We found that LEW rats exhibited higher novelty- and AMPH-induced locomotion, but F344 rats exhibited greater AMPH-induced rearing and stereotypy. An initial habituation session with i.v. saline minimized the strain differences in AMPH-induced behaviors except that the more frequent AMPH-induced rearing in F344 rats persisted. Strain differences in DAT total protein and basal activity were also observed, with LEW rats having less protein and slower in vivo clearance of locally-applied DA in dSTR and NAc. AMPH inhibited in vivo DA clearance in dSTR and NAc of both strains, but to a greater extent in F344 rats. Taken together, the lower basal DAT function in LEW rats is consistent with their greater novelty-induced locomotor activation, whereas the greater inhibition of DA clearance by AMPH in F344 rats is consistent with their marked AMPH-induced rearing behavior. PMID:17395161

  3. Adaptive locomotor behavior in larval zebrafish.

    PubMed

    Portugues, Ruben; Engert, Florian

    2011-01-01

    In this study we report that larval zebrafish display adaptive locomotor output that can be driven by unexpected visual feedback. We develop a new assay that addresses visuomotor integration in restrained larval zebrafish. The assay involves a closed-loop environment in which the visual feedback a larva receives depends on its own motor output in a way that resembles freely swimming conditions. The experimenter can control the gain of this closed feedback loop, so that following a given motor output the larva experiences more or less visual feedback depending on whether the gain is high or low. We show that increases and decreases in this gain setting result in adaptive changes in behavior that lead to a generalized decrease or increase of motor output, respectively. Our behavioral analysis shows that both the duration and tail beat frequency of individual swim bouts can be modified, as well as the frequency with which bouts are elicited. These changes can be implemented rapidly, following an exposure to a new gain of just 175 ms. In addition, modifications in some behavioral parameters accumulate over tens of seconds and effects last for at least 30 s from trial to trial. These results suggest that larvae establish an internal representation of the visual feedback expected from a given motor output and that the behavioral modifications are driven by an error signal that arises from the discrepancy between this expectation and the actual visual feedback. The assay we develop presents a unique possibility for studying visuomotor integration using imaging techniques available in the larval zebrafish.

  4. Adaptive Locomotor Behavior in Larval Zebrafish

    PubMed Central

    Portugues, Ruben; Engert, Florian

    2011-01-01

    In this study we report that larval zebrafish display adaptive locomotor output that can be driven by unexpected visual feedback. We develop a new assay that addresses visuomotor integration in restrained larval zebrafish. The assay involves a closed-loop environment in which the visual feedback a larva receives depends on its own motor output in a way that resembles freely swimming conditions. The experimenter can control the gain of this closed feedback loop, so that following a given motor output the larva experiences more or less visual feedback depending on whether the gain is high or low. We show that increases and decreases in this gain setting result in adaptive changes in behavior that lead to a generalized decrease or increase of motor output, respectively. Our behavioral analysis shows that both the duration and tail beat frequency of individual swim bouts can be modified, as well as the frequency with which bouts are elicited. These changes can be implemented rapidly, following an exposure to a new gain of just 175 ms. In addition, modifications in some behavioral parameters accumulate over tens of seconds and effects last for at least 30 s from trial to trial. These results suggest that larvae establish an internal representation of the visual feedback expected from a given motor output and that the behavioral modifications are driven by an error signal that arises from the discrepancy between this expectation and the actual visual feedback. The assay we develop presents a unique possibility for studying visuomotor integration using imaging techniques available in the larval zebrafish. PMID:21909325

  5. Muscle pain in athletes with locomotor disability.

    PubMed

    Bernardi, Marco; Castellano, Vincenzo; Ferrara, Michael S; Sbriccoli, Paola; Sera, Francesco; Marchetti, Marco

    2003-02-01

    Athletes with locomotor disabilities (LDA) participate in many competitive sport activities, yet little is known about sport-related muscle pain (SRMP). This study assessed the prevalence, determinants, and main characteristics of SRMP in LDA. A cross-disability epidemiological survey was used to investigate the occurrence of SRMP during the previous year by using a questionnaire administrated by medical doctors. SRMP was defined as any muscle pain experienced during the past 12 months that either occurred during sport activity (training or competition) and/or was reported as a consequence of physical exercise, causing discomfort for at least 1 d and not related to systemic disease. A total of 227 LDA were recruited randomly from the population (567 LDA) who participated in selected National sports events (including swimming, athletics, wheelchair basketball matches, and others) organized by the Italian Federation of Sports for Disabled. Collected data were statistically analyzed with univariate and multivariate logistic regression models to identify possible determinants of SRMP, through the estimate of the prevalence odds ratios. The SRMP period prevalence rate was equal to 50.7% (95% confidence interval (44.0-57.4%)), ranging from 47.0% (swimmers) to 58.8% (basketball athletes). In 71.1% of cases, SRMP lasted less than 1 wk and only 8.7% experienced pain for more than 1 month. SRMP had a higher prevalence in amputees (75.0%) and spinal cord injured LDA (58.1%) than the other groups. There was increased prevalence rate of SRMP with increased training volume. The multivariate logistic regression model showed disorder type, body mass index, and training volume as determinants of SRMP. Prospective studies could be devised to assess the role of anthropometric characteristics and training volume as risk factors of SRMP.

  6. Removing sensory input disrupts spinal locomotor activity in the early postnatal period

    PubMed Central

    Acevedo, JeanMarie; Díaz-Ríos, Manuel

    2013-01-01

    Motor patterns driving rhythmic movements of our lower limbs during walking are generated by groups of neurons within the spinal cord, called central pattern generators (CPGs). After suffering a spinal cord injury (SCI), many descending fibers from our brain are severed or become nonfunctional which leaves the spinal CPG network without its initiating drive. Recent studies are focusing on the importance of maintaining sensory stimulation to the legs on SCI patients as a way to initiate and control the CPG locomotor network. We began assessing the role of sensory feedback to the locomotor CPG network by using a neonatal mouse spinal cord preparation were the lower limbs are still attached. Removing sensory feedback coming from the hindlimbs by way of a lower lumbar transection or by ventral root denervation revealed a positive correlation in the ability of sensory input deprivation to disrupt ongoing locomotor activity on older versus younger animals. The differences in the motor responses as a function of age could be correlated with the loss of excitatory activity from sensory afferents. Continued studies on this field could eventually provide key information that translates in the design of novel therapeutic strategies to treat patients that have suffered a SCI. PMID:24043359

  7. Alterations in locomotor activity induced by radioprotective doses of 16,16-dimethyl prostaglandin E2

    SciTech Connect

    Landauer, M.R.; Walden, T.L.; Davis, H.D.; Dominitz, J.A.

    1987-01-01

    16,16-Dimethyl prostaglandin E2 (DiPGE2) is an effective radioprotectant when administered before irradiation. A notable side effect of this compound is sedation. In separate experiments, the dose-response determinations of the time course of locomotor activity and 30-day survival after 10 Gy gamma irradiation (LD100) were made. Adult male CD2F1 mice were injected subcutaneously with vehicle or DiPGE2 in doses ranging from 0.01 to 40 micrograms per mouse. A dose of 0.01 micrograms did not result in alterations in locomotor behaviour or enhance survival. Doses greater than 1 microgram produced ataxia and enhanced radiation survival in a dose-dependent fashion. Full recovery of locomotor activity did not occur until 6 and 30 hr after injection for the 10 microgram and 40 microgram groups, respectively. Radioprotection was observed when DiPGE2 was administered preirradiation but not postirradiation. Doses of 1 and 10 micrograms were maximally effective as a radioprotectant if injected 5 min prior to irradiation (80%-90% survival). A dose of 40 micrograms resulted in 100% survival when injected 5-30 min before irradiation. Therefore, increasing doses of DiPGE2 resulted in an enhanced effectiveness as a radioprotectant. However, the doses that were the most radioprotective were also the most debilitating to the animal.

  8. Ibogaine enhances the expression of locomotor sensitization in rats chronically treated with cocaine.

    PubMed

    Szumlinski, K K; Maisonneuve, I M; Glick, S D

    1999-07-01

    Pretreatment (19 h) with the putative antiaddictive agent, ibogaine, has been shown previously to potentiate cocaine-induced locomotion in rats. The present study demonstrates that the magnitude of this effect of ibogaine is dependent on the previous cocaine history of the animal, on the time following ibogaine treatment, and on the number of ibogaine treatments. Compared to rats with no previous cocaine experience, ibogaine pretreatment (40 mg/kg, IP, 19 h earlier) markedly enhanced the expression of locomotor sensitization in response to a cocaine challenge injection (7.5 mg/kg) in rats that were chronically treated with cocaine (15 mg/ kg, IP, daily for 5 days). Tolerance to cocaine-induced locomotor sensitization appeared to occur in vehicle-pretreated chronic cocaine controls. Following a second series of identical treatments (beginning 3-4 days after the initial treatment series), locomotor responding to the cocaine challenge was further enhanced by a second ibogaine injection in chronically cocaine-treated animals. Twenty-four hours later, when animals were challenged again with cocaine in the absence of any further ibogaine pretreatment, the effect of ibogaine had dissipated. Consistent with previous studies from this laboratory, these data demonstrate that ibogaine can enhance sensitivity to the psychomotor stimulant effect of cocaine. The results of the present study further indicate that the extent of this effect depends on the animal's history of exposure to both ibogaine and cocaine.

  9. Neurotensin receptor antagonist administered during cocaine withdrawal decreases locomotor sensitization and conditioned place preference.

    PubMed

    Felszeghy, Klara; Espinosa, José Manuel; Scarna, Hélène; Bérod, Anne; Rostène, William; Pélaprat, Didier

    2007-12-01

    Chronic use of psychostimulants induces enduringly increased responsiveness to a subsequent psychostimulant injection and sensitivity to drug-associated cues, contributing to drug craving and relapse. Neurotensin (NT), a neuropeptide functionally linked to dopaminergic neurons, was suggested to participate in these phenomena. We and others have reported that SR 48692, an NT receptor antagonist, given in pre- or co-treatments with cocaine or amphetamine, alters some behavioral effects of these drugs in rats. However, its efficacy when applied following repeated cocaine administration remains unknown. We, therefore, evaluated the ability of SR 48692, administered after a cocaine regimen, to interfere with the expression of locomotor sensitization and conditioned place preference (CPP) in rats. We demonstrated that the expression of locomotor sensitization, induced by four cocaine injections (15 mg/kg, i.p.) every other day and a cocaine challenge 1 week later, was attenuated by a subsequent 2-week daily administration of SR 48692 (1 mg/kg, i.p.). Furthermore, the expression of cocaine-induced CPP was suppressed by a 10-day SR 48692 treatment started after the conditioning period (four 15 mg/kg cocaine injections every other day). Taken together, our data show that a chronic SR 48692 treatment given after a cocaine regimen partly reverses the expression of locomotor sensitization and CPP in the rat, suggesting that NT participates in the maintenance of these behaviors. Our results support the hypothesis that targeting neuromodulatory systems, such as the NT systems may offer new strategies in the treatment of drug addiction.

  10. Male accessory gland substances from Aedes albopictus affect the locomotor activity of Aedes aegypti females.

    PubMed

    Lima-Camara, Tamara Nunes; Codeço, Claudia Torres; Honório, Nildimar Alves; Bruno, Rafaela Vieira; Peixoto, Alexandre Afranio; Lounibos, Leon Philip

    2013-01-01

    Dengue is one of the world's most important mosquito-borne diseases and is usually transmitted by one of two vector species: Aedes aegypti or Aedes albopictus . These two diurnal mosquitoes are frequently found coexisting in similar habitats, enabling interactions between adults, such as cross-mating. The objective of this study was to assess cross-mating between Ae. aegypti females and Ae. albopictus males under artificial conditions and evaluate the locomotor activity of Ae. aegypti virgin females injected with male accessory gland (MAG) homogenates to infer the physiological and behavioural responses to interspecific mating. After seven days of exposure, 3.3-16% of Ae. aegypti females mated with Ae. albopictus males. Virgin Ae. aegypti females injected with conspecific and heterospecific MAGs showed a general decrease in locomotor activity compared to controls and were refractory to mating with conspecific males. The reduction in diurnal locomotor activity induced by injections of conspecific or heterospecific MAGs is consistent with regulation of female reproductive activities by male substances, which are capable of sterilising female Ae. aegypti through satyrisation by Ae. albopictus.

  11. Male accessory gland substances from Aedes albopictus affect the locomotor activity of Aedes aegypti females

    PubMed Central

    Lima-Camara, Tamara Nunes; Codeço, Claudia Torres; Honório, Nildimar Alves; Bruno, Rafaela Vieira; Peixoto, Alexandre Afranio; Lounibos, Leon Philip

    2013-01-01

    Dengue is one of the world’s most important mosquito-borne diseases and is usually transmitted by one of two vector species: Aedes aegypti or Aedes albopictus . These two diurnal mosquitoes are frequently found coexisting in similar habitats, enabling interactions between adults, such as cross-mating. The objective of this study was to assess cross-mating between Ae. aegypti females and Ae. albopictus males under artificial conditions and evaluate the locomotor activity of Ae. aegypti virgin females injected with male accessory gland (MAG) homogenates to infer the physiological and behavioural responses to interspecific mating. After seven days of exposure, 3.3-16% of Ae. aegypti females mated with Ae. albopictus males. Virgin Ae. aegypti females injected with conspecific and heterospecific MAGs showed a general decrease in locomotor activity compared to controls and were refractory to mating with conspecific males. The reduction in diurnal locomotor activity induced by injections of conspecific or heterospecific MAGs is consistent with regulation of female reproductive activities by male substances, which are capable of sterilising female Ae. aegypti through satyrisation by Ae. albopictus . PMID:24473799

  12. Impact of Tail Loss on the Behaviour and Locomotor Performance of Two Sympatric Lampropholis Skink Species

    PubMed Central

    Cromie, Gillian L.; Chapple, David G.

    2012-01-01

    Caudal autotomy is an anti-predator behaviour that is used by many lizard species. Although there is an immediate survival benefit, the subsequent absence of the tail may inhibit locomotor performance, alter activity and habitat use, and increase the individuals' susceptibility to future predation attempts. We used laboratory experiments to examine the impact of tail autotomy on locomotor performance, activity and basking site selection in two lizard species, the delicate skink (Lampropholis delicata) and garden skink (L. guichenoti), that occur sympatrically throughout southeastern Australia and are exposed to an identical suite of potential predators. Post-autotomy tail movement did not differ between the two Lampropholis species, although a positive relationship between the shed tail length and distance moved, but not the duration of movement, was observed. Tail autotomy resulted in a substantial decrease in sprint speed in both species (28–39%), although this impact was limited to the optimal performance temperature (30°C). Although L. delicata was more active than L. guichenoti, tail autotomy resulted in decreased activity in both species. Sheltered basking sites were preferred over open sites by both Lampropholis species, although this preference was stronger in L. delicata. Caudal autotomy did not alter the basking site preferences of either species. Thus, both Lampropholis species had similar behavioural responses to autotomy. Our study also indicates that the impact of tail loss on locomotor performance may be temperature-dependent and highlights that future studies should be conducted over a broad thermal range. PMID:22523555

  13. Perturbation schedule does not alter retention of a locomotor adaptation across days

    PubMed Central

    Hussain, Sara J.

    2014-01-01

    Motor adaptation in response to gradual vs. abrupt perturbation schedules may involve different neural mechanisms, potentially leading to different levels of motor memory. However, no study has investigated whether perturbation schedules alter memory of a locomotor adaptation across days. We measured adaptation and retention (memory) of altered interlimb symmetry during walking in two groups of participants over 2 days. On day 1, participants adapted to either a single, large perturbation (abrupt schedule) or a series of small perturbations that increased in size over time (gradual schedule). Retention was examined on day 2. On day 1, initial swing time and foot placement symmetry error sizes differed between groups but overall adaptation magnitudes were similar. On day 2, participants in both groups showed similar retention, readaptation, and aftereffect sizes, although there were some trends for improved memory in the abrupt group. These results conflict with previous data but are consistent with newer studies reporting no behavioral differences following adaptation using abrupt vs. gradual schedules. Although memory levels were very similar between groups, we cannot rule out the possibility that the neural mechanisms underlying this memory storage differ. Overall, it appears that adaptation of locomotor patterns via abrupt and gradual perturbation schedules produces similar expression of locomotor memories across days. PMID:24647433

  14. Meal schedule influences food restriction-induced locomotor sensitization to methamphetamine

    PubMed Central

    Sharpe, Amanda L.; Klaus, Joshua D.

    2015-01-01

    Rationale Traditional protocols for inducing sensitization to psychostimulants use an intermittent or “binge”-like drug administration, and binge eating behavior is comorbid with drug abuse in humans. Food restriction increases the reinforcing properties and self-administration of many drugs of abuse. Objective The present study tested the hypotheses that (1) food restriction induces sensitization to the locomotor stimulation observed in response to methamphetamine and (2) a binge-like feeding schedule during food restriction produces increased sensitization compared to equally restricted mice fed in three daily meals. Methods Male DBA/2J mice were fed ad libitum or were food restricted to either an 8% or 16% loss of body weight. Additionally, the food-restricted mice were divided into two groups that were fed in either one meal (binge) or three equal-sized meals (meal). After the reduced body weight was stable, mice were tested for locomotor activity following saline and methamphetamine (1 mg/kg) injections. Results Both 16% body weight loss groups exhibited sensitization to methamphetamine. Opposite to our hypothesis, the 8% meal but not the 8% binge food-restricted group demonstrated locomotor sensitization. Serum corticosterone levels were significantly higher in the meal-fed groups when compared to the binge- and ad libitum-fed groups. Conclusions These results support a role for feeding schedule and plasma corticosterone levels in food restriction-induced enhancement of the effects of methamphetamine. PMID:21750897

  15. The effect of early environmental manipulation on locomotor sensitivity and methamphetamine conditioned place preference reward.

    PubMed

    Hensleigh, E; Pritchard, L M

    2014-07-15

    Early life stress leads to several effects on neurological development, affecting health and well-being later in life. Instances of child abuse and neglect are associated with higher rates of depression, risk taking behavior, and an increased risk of drug abuse later in life. This study used repeated neonatal separation of rat pups as a model of early life stress. Rat pups were either handled and weighed as controls or separated for 180 min per day during postnatal days 2-8. In adulthood, male and female rats were tested for methamphetamine conditioned place preference reward and methamphetamine induced locomotor activity. Tissue samples were collected and mRNA was quantified for the norepinephrine transporter in the prefrontal cortex and the dopamine transporter in the nucleus accumbens. Results indicated rats given methamphetamine formed a conditioned place preference, but there was no effect of early separation or sex. Separated males showed heightened methamphetamine-induced locomotor activity, but there was no effect of early separation for females. Overall females were more active than males in response to both saline and methamphetamine. No differences in mRNA levels were observed across any conditions. These results suggest early neonatal separation affects methamphetamine-induced locomotor activity in a sex-dependent manner but has no effects on methamphetamine conditioned place preference.

  16. Reduced locomotor activity and exploratory behavior in CC chemokine receptor 4 deficient mice.

    PubMed

    Ambrée, Oliver; Klassen, Irene; Förster, Irmgard; Arolt, Volker; Scheu, Stefanie; Alferink, Judith

    2016-11-01

    Chemokines and their receptors are key regulators of immune cell trafficking and activation. Recent findings suggest that they may also play pathophysiological roles in psychiatric diseases like depression and anxiety disorders. The CC chemokine receptor 4 (CCR4) and its two ligands, CCL17 and CCL22, are functionally involved in neuroinflammation as well as anti-infectious and autoimmune responses. However, their influence on behavior remains unknown. Here we characterized the functional role of the CCR4-CCL17 chemokine-receptor axis in the modulation of anxiety-related behavior, locomotor activity, and object exploration and recognition. Additionally, we investigated social exploration of CCR4 and CCL17 knockout mice and wild type (WT) controls. CCR4 knockout (CCR4(-/-)) mice exhibited fewer anxiety-related behaviors in the elevated plus-maze, diminished locomotor activity, exploratory behavior, and social exploration, while their recognition memory was not affected. In contrast, CCL17 deficient mice did not show an altered behavior compared to WT mice regarding locomotor activity, anxiety-related behavior, social exploration, and object recognition memory. In the dark-light and object recognition tests, CCL17(-/-) mice even covered longer distances than WT mice. These data demonstrate a mechanistic or developmental role of CCR4 in the regulation of locomotor and exploratory behaviors, whereas the ligand CCL17 appears not to be involved in the behaviors measured here. Thus, either CCL17 and the alternative ligand CCL22 may be redundant, or CCL22 is the main activator of CCR4 in these processes. Taken together, these findings contribute to the growing evidence regarding the involvement of chemokines and their receptors in the regulation of behavior.

  17. Voluntary and reactive recruitment of locomotor muscle synergies during perturbed walking

    PubMed Central

    Chvatal, Stacie A.; Ting, Lena H.

    2012-01-01

    The modular control of muscles in groups, often referred to as muscle synergies, has been proposed to provide a motor repertoire of actions for the robust control of movement. However it is not clear whether muscle synergies identified in one task are also recruited by different neural pathways subserving other motor behaviors. We tested the hypothesis that voluntary and reactive modifications to walking in humans result from the recruitment of locomotor muscle synergies. We recorded the activity of 16 muscles in the right leg as subjects walked a 7.5 m path at two different speeds. To elicit a second motor behavior, midway through the path we imposed ramp and hold translation perturbations of the support surface in each of four cardinal directions. Variations in the temporal recruitment of locomotor muscle synergies could account for cycle-by-cycle variations in muscle activity across strides. Locomotor muscle synergies were also recruited in atypical phases of gait, accounting for both anticipatory gait modifications prior to perturbations and reactive feedback responses to perturbations. Our findings are consistent with the idea that a common pool of spatially-fixed locomotor muscle synergies can be recruited by different neural pathways, including the central pattern generator for walking, brainstem pathways for balance control, and cortical pathways mediating voluntary gait modifications. Together with electrophysiological studies, our work suggests that muscle synergies may provide a library of motor subtasks that can be flexibly recruited by parallel descending pathways to generate a variety of complex natural movements in the upper and lower limbs. PMID:22933805

  18. Obstacle avoidance locomotor tasks: adaptation, memory and skill transfer.

    PubMed

    Kloter, Evelyne; Dietz, Volker

    2012-05-01

    The aim of this study was to explore the neural basis of adaptation, memory and skill transfer during human stepping over obstacles. Whilst walking on a treadmill, subjects had to perform uni- and bilateral obstacle steps. Acoustic feedback information about foot clearance was provided. Non-noxious electrical stimuli were applied to the right tibial nerve during the mid-stance phase of the right leg, i.e. 'prior' to the right or 'during' the left leg swing over the obstacle. The electromyogram (EMG) responses evoked by these stimuli in arm and leg muscles are known to reflect the neural coordination during normal and obstacle steps. The leading and trailing legs rapidly adapted foot clearance during obstacle steps with small further changes when the same obstacle condition was repeated. This adaptation was associated with a corresponding decrease in arm and leg muscle reflex EMG responses. Arm (but not leg) muscle EMG responses were greater when the stimulus was applied 'during' obstacle crossing by the left leg leading compared with stimulation 'prior' to right leg swing over the obstacle. A corresponding difference existed in arm muscle background EMG. The results indicate that, firstly, the somatosensory information gained by the performance and adaptation of uni- and bilateral obstacle stepping becomes transferred to the trailing leg in a context-specific manner. Secondly, EMG activity in arm and leg muscles parallels biomechanical adaptation of foot clearance. Thirdly, a consistently high EMG activity in the arm muscles during swing over the obstacle is required for equilibrium control. Thus, such a precision locomotor task is achieved by a context-specific, coordinated activation of arm and leg muscles for performance and equilibrium control that includes adaptation, memory and skill transfer.

  19. Quantitative analysis of the evolution of novelty in cinema through crowdsourced keywords

    PubMed Central

    Sreenivasan, Sameet

    2013-01-01

    The generation of novelty is central to any creative endeavor. Novelty generation and the relationship between novelty and individual hedonic value have long been subjects of study in social psychology. However, few studies have utilized large-scale datasets to quantitatively investigate these issues. Here we consider the domain of American cinema and explore these questions using a database of films spanning a 70 year period. We use crowdsourced keywords from the Internet Movie Database as a window into the contents of films, and prescribe novelty scores for each film based on occurrence probabilities of individual keywords and keyword-pairs. These scores provide revealing insights into the dynamics of novelty in cinema. We investigate how novelty influences the revenue generated by a film, and find a relationship that resembles the Wundt-Berlyne curve. We also study the statistics of keyword occurrence and the aggregate distribution of keywords over a 100 year period. PMID:24067890

  20. Altitudinal gradients, plant hybrid zones and evolutionary novelty

    PubMed Central

    Abbott, Richard J.; Brennan, Adrian C.

    2014-01-01

    Altitudinal gradients are characterized by steep changes of the physical and biotic environment that present challenges to plant adaptation throughout large parts of the world. Hybrid zones may form where related species inhabit different neighbouring altitudes and can facilitate interspecific gene flow and potentially the breakdown of species barriers. Studies of such hybrid zones can reveal much about the genetic basis of adaptation to environmental differences stemming from changes in altitude and the maintenance of species divergence in the face of gene flow. Furthermore, owing to recombination and transgressive effects, such hybrid zones can be sources of evolutionary novelty. We document plant hybrid zones associated with altitudinal gradients and emphasize similarities and differences in their structure. We then focus on recent studies of a hybrid zone between two Senecio species that occur at high and low altitude on Mount Etna, Sicily, showing how adaptation to local environments and intrinsic selection against hybrids act to maintain it. Finally, we consider the potential of altitudinal hybrid zones for generating evolutionary novelty through adaptive introgression and hybrid speciation. Examples of homoploid hybrid species of Senecio and Pinus that originated from altitudinal hybrid zones are discussed. PMID:24958920

  1. Pair housing induced feeding suppression: individual housing not novelty.

    PubMed

    Lopak, V; Eikelboom, R

    Male rats that are moved from individual to pair housing suppress their feeding for a few days [O'Connor R, Eikelboom R. The effects of changes in housing on feeding and wheel running. Physiol Behav 2000;68:361-371]. The present study explored whether the suppression was a result of the period of individual housing or the novelty of the other animal. Two groups of 16 rats were pair-housed and one group of rats was individually housed for 21 days. The individually housed rats were then pair-housed (IP group) and rats in one of the pair-housed groups were re-housed with novel partners (NP group), while rats in the other pair-housed group remained with the same partner (SP group). Feeding was suppressed only for rats in the IP group, suggesting that the novelty of the partner did not suppress feeding, but rather, the change from individual to pair housing did. Water consumption was also measured, but was unaffected by the re-housing manipulation.

  2. Altitudinal gradients, plant hybrid zones and evolutionary novelty.

    PubMed

    Abbott, Richard J; Brennan, Adrian C

    2014-08-05

    Altitudinal gradients are characterized by steep changes of the physical and biotic environment that present challenges to plant adaptation throughout large parts of the world. Hybrid zones may form where related species inhabit different neighbouring altitudes and can facilitate interspecific gene flow and potentially the breakdown of species barriers. Studies of such hybrid zones can reveal much about the genetic basis of adaptation to environmental differences stemming from changes in altitude and the maintenance of species divergence in the face of gene flow. Furthermore, owing to recombination and transgressive effects, such hybrid zones can be sources of evolutionary novelty. We document plant hybrid zones associated with altitudinal gradients and emphasize similarities and differences in their structure. We then focus on recent studies of a hybrid zone between two Senecio species that occur at high and low altitude on Mount Etna, Sicily, showing how adaptation to local environments and intrinsic selection against hybrids act to maintain it. Finally, we consider the potential of altitudinal hybrid zones for generating evolutionary novelty through adaptive introgression and hybrid speciation. Examples of homoploid hybrid species of Senecio and Pinus that originated from altitudinal hybrid zones are discussed.

  3. The Evolution of Novelty in Conserved Gene Families

    PubMed Central

    Markov, Gabriel V.; Sommer, Ralf J.

    2012-01-01

    One of the major aims of contemporary evolutionary biology is the understanding of the current pattern of biological diversity. This involves, first, the description of character distribution at various nodes of the phylogenetic tree of life and, second, the functional explanation of such changes. The analysis of character distribution is a powerful tool at both the morphological and molecular levels. Recent high-throughput sequencing approaches provide new opportunities to study the genetic architecture of organisms at the genome-wide level. In eukaryotes, one overarching finding is the absence of simple correlations of gene count and biological complexity. Instead, the domain architecture of proteins is becoming a central focus for large-scale evolutionary innovations. Here, we review examples of the evolution of novelty in conserved gene families in insects and nematodes. We highlight how in the absence of whole-genome duplications molecular novelty can arise, how members of gene families have diversified at distinct mechanistic levels, and how gene expression can be maintained in the context of multiple innovations in regulatory mechanisms. PMID:22779028

  4. Behavioral cross-sensitization between DOCA-induced sodium appetite and cocaine-induced locomotor behavior

    PubMed Central

    Acerbo, Martin J.; Johnson, Alan Kim

    2011-01-01

    Behavioral sensitization involves increases in the magnitude of a response to a stimulus after repeated exposures to the same response initiator. Administration of psychomotor stimulants and the induction of appetitive motivational states associated with natural reinforcers like sugar and salt are among experimental manipulations producing behavioral sensitization. In rats, repeated administration of the mineralocorticoid agonist deoxycorticosterone acetate (DOCA) initially induces incremental increases in daily hypertonic saline consumption (i.e., sensitization of sodium appetite) in spite of the retention of sodium. The present studies investigated whether sodium appetite sensitization induced by DOCA shares mechanisms similar to those of psychomotor stimulant-induced sensitization, and whether there is evidence for reciprocal cross-sensitization. In Experiments 1 and 3, rats received control or cocaine treatments to induce locomotor sensitization. A week later DOCA (or vehicle) was administered to generate a sodium appetite. Animals pretreated with cocaine showed a greater sodium appetite. In Experiment 2, the order of the putative sensitizing treatments was reversed. Rats first received either a series of DOCA or vehicle treatments either with or without access to saline and were later tested for sensitization of the locomotor response to cocaine. Animals pretreated with DOCA without access to saline showed greater locomotor responses to cocaine than animals receiving vehicle treatments. Together these experiments indicate that treatments generating a sustained salt appetite and producing cocaine-induced psychomotor responses show reciprocal behavioral cross-sensitization. The underlying mechanisms accounting for this relationship may be the fact that psychostimulants and an unresolved craving for sodium can act as potent stressors. PMID:21352848

  5. Behavioral cross-sensitization between DOCA-induced sodium appetite and cocaine-induced locomotor behavior.

    PubMed

    Acerbo, Martin J; Johnson, Alan Kim

    2011-05-01

    Behavioral sensitization involves increases in the magnitude of a response to a stimulus after repeated exposures to the same response initiator. Administration of psychomotor stimulants and the induction of appetitive motivational states associated with natural reinforcers like sugar and salt are among experimental manipulations producing behavioral sensitization. In rats, repeated administration of the mineralocorticoid agonist deoxycorticosterone acetate (DOCA) initially induces incremental increases in daily hypertonic saline consumption (i.e., sensitization of sodium appetite) in spite of the retention of sodium. The present studies investigated whether sodium appetite sensitization induced by DOCA shares mechanisms similar to those of psychomotor stimulant-induced sensitization, and whether there is evidence for reciprocal cross-sensitization. In Experiments 1 and 3, rats received control or cocaine treatments to induce locomotor sensitization. A week later DOCA (or vehicle) was administered to generate a sodium appetite. Animals pretreated with cocaine showed a greater sodium appetite. In Experiment 2, the order of the putative sensitizing treatments was reversed. Rats first received either a series of DOCA or vehicle treatments either with or without access to saline and were later tested for sensitization of the locomotor response to cocaine. Animals pretreated with DOCA without access to saline showed greater locomotor responses to cocaine than animals receiving vehicle treatments. Together these experiments indicate that treatments generating a sustained salt appetite and producing cocaine-induced psychomotor responses show reciprocal behavioral cross-sensitization. The underlying mechanisms accounting for this relationship may be the fact that psychostimulants and an unresolved craving for sodium can act as potent stressors.

  6. The mesencephalic locomotor region sends a bilateral glutamatergic drive to hindbrain reticulospinal neurons in a tetrapod

    PubMed Central

    Ryczko, Dimitri; Auclair, Francois; Cabelguen, Jean‐Marie

    2015-01-01

    In vertebrates, stimulation of the mesencephalic locomotor region (MLR) on one side evokes symmetrical locomotor movements on both sides. How this occurs was previously examined in detail in a swimmer using body undulations (lamprey), but in tetrapods the downstream projections from the MLR to brainstem neurons are not fully understood. Here we examined the brainstem circuits from the MLR to identified reticulospinal neurons in the salamander Notophthalmus viridescens. Using neural tracing, we show that the MLR sends bilateral projections to the middle reticular nucleus (mRN, rostral hindbrain) and the inferior reticular nucleus (iRN, caudal hindbrain). Ca2+ imaging coupled to electrophysiology in in vitro isolated brains revealed very similar responses in reticulospinal neurons on both sides to a unilateral MLR stimulation. As the strength of MLR stimulation was increased, the responses increased in size in reticulospinal neurons of the mRN and iRN, but the responses in the iRN were smaller. Bath‐application or local microinjections of glutamatergic antagonists markedly reduced reticulospinal neuron responses, indicating that the MLR sends glutamatergic inputs to reticulospinal neurons. In addition, reticulospinal cells responded to glutamate microinjections and the size of the responses paralleled the amount of glutamate microinjected. Immunofluorescence coupled with anatomical tracing confirmed the presence of glutamatergic projections from the MLR to reticulospinal neurons. Overall, we show that the brainstem circuits activated by the MLR in the salamander are organized similarly to those previously described in lampreys, indicating that the anatomo‐physiological features of the locomotor drive are well conserved in vertebrates. J. Comp. Neurol. 524:1361–1383, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26470600

  7. Influence of the Novelty-Seeking Endophenotype on the Rewarding Effects of Psychostimulant Drugs in Animal Models.

    PubMed

    Arenas, M Carmen; Aguilar, María A; Montagud-Romero, Sandra; Mateos-García, Ana; Navarro-Francés, Concepción I; Miñarro, José; Rodríguez-Arias, Marta

    2016-01-01

    Novelty seeking (NS), defined as a tendency to pursue novel and intense emotional sensations and experiences, is one of the most relevant individual factors predicting drug use among humans. High novelty seeking (HNS) individuals present an increased risk of drug use compared to low novelty seekers. The NS endophenotype may explain some of the differences observed among individuals exposed to drugs of abuse in adolescence. However, there is little research about the particular response of adolescents to drugs of abuse in function of this endophenotype, and the data that do exist are inconclusive. The present work reviews the literature regarding the influence of NS on psychostimulant reward, with particular focus on adolescent subjects. First, the different animal models of NS and the importance of this endophenotype in adolescence are discussed. Later, studies that have used the most common animal models of reward (self-administration, conditioned place preference paradigms) to evaluate how the NS trait influences the rewarding effects of psychostimulants are reviewed. Finally, possible explanations for the enhanced risk of developing substance dependence among HNS individuals are discussed. In conclusion, the studies referred to in this review show that the HNS trait is associated with: (1) increased initial sensitivity to the rewarding effects of psychostimulants, (2) a higher level of drug craving when the subject is exposed to the environmental cues associated with the drug, and (3) enhanced long-term vulnerability to relapse to drug consumption after prolonged abstinence.

  8. Influence of the Novelty-Seeking Endophenotype on the Rewarding Effects of Psychostimulant Drugs in Animal Models

    PubMed Central

    Carmen Arenas, M.; Aguilar, María A.; Montagud-Romero, Sandra; Mateos-García, Ana; Navarro-Francés, Concepción I.; Miñarro, José; Rodríguez-Arias, Marta

    2016-01-01

    Novelty seeking (NS), defined as a tendency to pursue novel and intense emotional sensations and experiences, is one of the most relevant individual factors predicting drug use among humans. High novelty seeking (HNS) individuals present an increased risk of drug use compared to low novelty seekers. The NS endophenotype may explain some of the differences observed among individuals exposed to drugs of abuse in adolescence. However, there is little research about the particular response of adolescents to drugs of abuse in function of this endophenotype, and the data that do exist are inconclusive. The present work reviews the literature regarding the influence of NS on psychostimulant reward, with particular focus on adolescent subjects. First, the different animal models of NS and the importance of this endophenotype in adolescence are discussed. Later, studies that have used the most common animal models of reward (self-administration, conditioned place preference paradigms) to evaluate how the NS trait influences the rewarding effects of psychostimulants are reviewed. Finally, possible explanations for the enhanced risk of developing substance dependence among HNS individuals are discussed. In conclusion, the studies referred to in this review show that the HNS trait is associated with: (1) increased initial sensitivity to the rewarding effects of psychostimulants, (2) a higher level of drug craving when the subject is exposed to the environmental cues associated with the drug, and (3) enhanced long-term vulnerability to relapse to drug consumption after prolonged abstinence. PMID:26391743

  9. Effects of changing housing conditions on mangabey behavior (Cercocebus atys): spatial density, housing quality, and novelty effects

    PubMed Central

    Crast, Jessica; Bloomsmith, Mollie A.; Jonesteller, Trina

    2015-01-01

    The separate influences of spatial density and housing quality on the behavior of captive animals are difficult to measure because the two factors are often intrinsically linked. Here, we recorded affiliative and agonistic behavior in adult sooty mangabeys in various housing situations, testing spatial density and housing quality changes separately (N=26 experienced spatial density changes; N=12 experienced housing quality changes). We varied spatial density by 50% while holding housing quality constant and we varied housing quality while holding spatial density constant (achieved by comparing two types of run-housing that varied in the amount of visual privacy and outdoor access). Each housing condition was one month in duration. Prior to collecting data in each housing condition, we evaluated the subjects’ initial responses to the change in housing environment during two-week novelty periods. Affiliative behavior did not change during the novelty periods. Agonistic behavior initially increased slightly when spatial density increased and it decreased significantly when spatial density decreased; it also decreased when subjects moved to housing that offered more visual privacy and outdoor space, indicating that the mangabeys were sensitive to these housing changes. After the novelty periods, affiliative behavior increased under higher spatial density, but remained unchanged across housing quality conditions; agonistic behavior remained unchanged across all conditions. Results suggest that a prolonged increase in spatial density led the mangabeys to adopt a tension-reduction coping strategy, in which the increase in affiliative behavior alleviates a presumed increase in social tension. Reducing visual privacy and choice did not affect the mangabeys’ behavior, post-novelty period. Thus, like many other primates, the mangabeys managed tension by flexibly adapting to changes in their housing environment in ways that reduce the risk of severe aggression. This study

  10. Is it new? Personal and contextual influences on perceptions of novelty and creativity.

    PubMed

    Zhou, Jing; Wang, Xiaoye May; Song, Lynda Jiwen; Wu, Junfeng

    2017-02-01

    Novelty recognition is the crucial starting point for extracting value from the ideas generated by others. In this paper we develop an associative evaluation account for how personal and contextual factors motivate individuals to perceive novelty and creativity. We report 4 studies that systematically tested hypotheses developed from this perspective. Study 1 (a laboratory experiment) showed that perceivers' regulatory focus, as an experimentally induced state, affected novelty perception. Study 2 (a field study) found that perceivers' promotion focus and prevention focus, measured as chronic traits, each interacted with normative level of novelty and creativity: perceivers who scored higher on promotion focus perceived more novelty (or creativity) in novel (or creative) targets than those who scored lower, whereas perceivers who scored higher on prevention focus perceived less novelty (or creativity) in novel (or creative) targets than those who scored lower. Study 3 (a field study) showed that organizational culture affected the perception of novelty and creativity. Study 4 (a laboratory experiment) found perceiver-by-idea-by-context 3-way interaction effects: for perceivers with prevention focus, the positive relation between normative level of novelty and novelty ratings was weakened in the loss-framing condition versus the gain-framing condition. We discuss implications of the findings for future research and management practice. (PsycINFO Database Record

  11. Comparison of outliers and novelty detection to identify ionospheric TEC irregularities during geomagnetic storm and substorm

    NASA Astrophysics Data System (ADS)

    Pattisahusiwa, Asis; Houw Liong, The; Purqon, Acep

    2016-08-01

    In this study, we compare two learning mechanisms: outliers and novelty detection in order to detect ionospheric TEC disturbance by November 2004 geomagnetic storm and January 2005 substorm. The mechanisms are applied by using v-SVR learning algorithm which is a regression version of SVM. Our results show that both mechanisms are quiet accurate in learning TEC data. However, novelty detection is more accurate than outliers detection in extracting anomalies related to geomagnetic events. The detected anomalies by outliers detection are mostly related to trend of data, while novelty detection are associated to geomagnetic events. Novelty detection also shows evidence of LSTID during geomagnetic events.

  12. The hippocampus is sensitive to the mismatch in novelty between items and their contexts.

    PubMed

    Thakral, Preston P; Yu, Sarah S; Rugg, Michael D

    2015-03-30

    In previous functional magnetic resonance imaging (fMRI) studies of continuous recognition memory it was reported that new items elicit greater hippocampal activity than old (repeated) items (hippocampal 'novelty' effects). Rather than reflecting recency differences between new and old items, hippocampal novelty effects may instead reflect the novelty of the association between test items and the experimental context, or a mismatch in the novelty of the test item and the context. The present continuous recognition study assessed these possibilities by manipulating item-context associations on a trial-by-trial basis. Each trial comprised the presentation of an object-word (context-item) pair. Repeated items were paired either with the same context as on their first presentation, a different but previously presented context, or a new context. The task was to judge whether each item was old or new, regardless of the study status of the associated context. We found no evidence that hippocampal novelty effects reflected either item and context recency, or the novelty of the item-context association. Rather, enhanced hippocampal activity was elicited when the novelty of the item and its context mismatched. These findings support the possibility that hippocampal novelty effects reflect, at least in part, the disjunction in novelty between test items and their contexts. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Modular diversification of the locomotor system in damselfishes (Pomacentridae).

    PubMed

    Aguilar-Medrano, Rosalía; Frédérich, Bruno; Barber, Paul H

    2016-05-01

    As fish move and interact with their aquatic environment by swimming, small morphological variations of the locomotor system can have profound implications on fitness. Damselfishes (Pomacentridae) have inhabited coral reef ecosystems for more than 50 million years. As such, habitat preferences and behavior could significantly constrain the morphology and evolvability of the locomotor system. To test this hypothesis, we used phylogenetic comparative methods on morphometric, ecological and behavioral data. While body elongation represented the primary source of variation in the locomotor system of damselfishes, results also showed a diverse suite of morphological combinations between extreme morphologies. Results show clear associations between behavior, habitat preferences, and morphology, suggesting ecological constraints on shape diversification of the locomotor system. In addition, results indicate that the three modules of the locomotor system are weakly correlated, resulting in versatile and independent characters. These results suggest that Pomacentridae is shape may result from the interaction between (1) integrated parts of morphological variation that maintain overall swimming ability and (2) relatively independent parts of the morphology that facilitate adaptation and diversification. © 2016 Wiley Periodicals, Inc.

  14. Effects of stress and tranylcypromine on amphetamine-induced locomotor activity and GABA(B) receptor function in rat brain.

    PubMed

    Sands, S A; Reisman, S A; Enna, S J

    2003-01-17

    Modification in gamma-aminobutyric acid-B (GABA(B)) receptors may contribute to the symptoms of some neurological and psychiatric disorders and to the clinical response to psychotherapeutics. The present study was undertaken to determine whether chronic administration of tranylcypromine (TCP), an antidepressant, and chronic stress influence GABA(B) receptor function in rat brain. The results indicate that TCP treatment, but not stress, increases GABA(B) receptor activity in the cerebral cortex, as measured by baclofen-stimulated GTPgammaS binding. In addition, chronic administration of TCP enhances significantly the locomotor response to a single dose of amphetamine, an effect that is abolished by restraint stress. These results indicate that although TCP administration modifies brain GABA(B) receptor activity, which may contribute to the antidepressant response to this agent, this effect is unrelated to the interaction of stress and TCP treatment on the locomotor response to amphetamine.

  15. Prefrontal microRNA-221 Mediates Environmental Enrichment-Induced Increase of Locomotor Sensitivity to Nicotine

    PubMed Central

    Gomez, Adrian M.; Altomare, Diego; Sun, Wei-Lun; Midde, Narasimha M.; Ji, Hao; Shtutman, Michael; Turner, Jill R.; Creek, Kim E.

    2016-01-01

    Background: Environmental enrichment alters susceptibility in developing drug addiction. We have demonstrated that rats raised in an enriched condition are more sensitive than rats raised in an impoverished condition to nicotine-induced locomotor activity, and this is associated with alterations of phosphorylated extracellular signal-regulated kinase 1/2 within the prefrontal cortex. This study determined the impact of microRNA-221 in the prefrontal cortex on phosphorylated extracellular signal-regulated kinase 1/2 and the enriched environment-dependent behavioral changes in response to nicotine. Methods: A microRNA array was conducted to profile microRNA expression in the prefrontal cortex of enriched condition and impoverished condition rats in response to repeated nicotine (0.35mg/kg, s.c.) administration. microRNA-221 in the prefrontal cortex, nucleus accumbens, and striatum was further verified by quantitative real-time PCR. Lentiviral-mediated overexpression of microRNA-221 in PC12 cells and the medial prefrontal cortex was performed to determine the effects of microRNA-221 on nicotine-mediated phosphorylated extracellular signal-regulated kinase 1/2, phosphorylated cAMP-response element-binding protein, and locomotor activity. Results: microRNA-221 was profoundly upregulated in the prefrontal cortex but not in nucleus accumbens and striatum of enriched condition rats relative to impoverished condition rats following repeated administration of nicotine. Overexpression of lentiviral-microRNA-221 attenuated nicotine-induced increase in phosphorylated extracellular signal-regulated kinase 1/2 in PC12 cells. Lentiviral-microRNA-221 overexpression in the medial prefrontal cortex further increased locomotor activity in impoverished condition but not in enriched condition rats in response to repeated nicotine administration. Accordingly, lentiviral-microRNA-221 attenuated nicotine-induced increases in phosphorylated extracellular signal-regulated kinase 1/2 and

  16. Profilin2 contributes to synaptic vesicle exocytosis, neuronal excitability, and novelty-seeking behavior

    PubMed Central

    Pilo Boyl, Pietro; Di Nardo, Alessia; Mulle, Christophe; Sassoè-Pognetto, Marco; Panzanelli, Patrizia; Mele, Andrea; Kneussel, Matthias; Costantini, Vivian; Perlas, Emerald; Massimi, Marzia; Vara, Hugo; Giustetto, Maurizio; Witke, Walter

    2007-01-01

    Profilins are actin binding proteins essential for regulating cytoskeletal dynamics, however, their function in the mammalian nervous system is unknown. Here, we provide evidence that in mouse brain profilin1 and profilin2 have distinct roles in regulating synaptic actin polymerization with profilin2 preferring a WAVE-complex-mediated pathway. Mice lacking profilin2 show a block in synaptic actin polymerization in response to depolarization, which is accompanied by increased synaptic excitability of glutamatergic neurons due to higher vesicle exocytosis. These alterations in neurotransmitter release correlate with a hyperactivation of the striatum and enhanced novelty-seeking behavior in profilin2 mutant mice. Our results highlight a novel, profilin2-dependent pathway, regulating synaptic physiology, neuronal excitability, and complex behavior. PMID:17541406

  17. Perception--action coupling model for human locomotor pointing.

    PubMed

    de Rugy, A; Taga, G; Montagne, G; Buekers, M J; Laurent, M

    2002-08-01

    How do humans achieve the precise positioning of the feet during walking, for example, to reach the first step of a stairway? We addressed this question at the visuomotor integration level. Based on the optical specification of the required adaptation, a dynamical system model of the visuomotor control of human locomotor pointing was devised for the positioning of a foot on a visible target on the floor during walking. Visuomotor integration consists of directly linking optical information to a motor command that specifically modulates step length in accordance with the ongoing dynamics of locomotor pattern generation. The adaptation of locomotion emerges from a perception-action coupling type of control based on temporal information rather than on feedforward planning of movements. The proposed model reproduces experimental results obtained for human locomotor pointing.

  18. Developing Sensorimotor Countermeasures to Mitigate Post-Flight Locomotor Dysfunction

    NASA Technical Reports Server (NTRS)

    Bloomberg, J. J.; Mulavara, A. P.; Cohen, H.; Miller, C. A.; Richards, J. T.; Houser, J.; McDonald, P. V.; Seidler, R. D.; Merkle, L. A.; Stelmach, G. E.

    2001-01-01

    Following spaceflight, crewmembers experience postural and locomotor instability. The magnitude and duration of post-flight sensorimotor disturbances increase with longer duration exposure to microgravity. These post-flight postural and locomotor alterations can pose a risk to crew safety and to mission objectives if nominal or emergency vehicle egress is required immediately following long-duration spaceflight. Gait instabilities could prevent or extend the time required to make an emergency egress from the Orbiter, Crew Return Vehicle or a future Martian lander leading to compromised mission objectives. We propose a countermeasure that aids in maintaining functional locomotor performance. This includes retaining the ability to perform vehicular egress and meet early mission objectives soon after landing on a planetary surface.

  19. Novelty detection applied to vibration data from a CX-100 wind turbine blade under fatigue loading

    NASA Astrophysics Data System (ADS)

    Dervilis, N.; Choi, M.; Antoniadou, I.; Farinholt, K. M.; Taylor, S. G.; Barthorpe, R. J.; Park, G.; Worden, K.; Farrar, C. R.

    2012-08-01

    The remarkable evolution of new generation wind turbines has led to a dramatic increase of wind turbine blade size. In turn, a reliable structural health monitoring (SHM) system will be a key factor for the successful implementation of such systems. Detection of damage at an early stage is a crucial issue as blade failure would be a catastrophic result for the entire wind turbine. In this study the SHM analysis will be based on experimental measurements of Frequency Response Functions (FRFs) extracted by using an input/output acquisition technique under a fatigue loading of a 9m CX-100 blade at the National Renewable Energy Laboratory (NREL) and National Wind Technology Center (NWTC) performed in the Los Alamos National Laboratory. The blade was harmonically excited at its first natural frequency using a Universal Resonant Excitation (UREX) system. For analysis, the Auto-Associative Neural Network (AANN) is a non-parametric method where a set of damage sensitive features gathered from the measured structure are used to train a network that acts as a novelty detector. This traditionally has a highly complex "bottleneck" structure with five layers in the AANN. In the current paper, a new attempt is also exploited based on an AANN with one hidden layer in order to reduce the theoretical and computational difficulties. Damage detection of composite bodies of blades is a "grand challenge" due to varying aerodynamic and gravitational loads and environmental conditions. A study of the noise tolerant capability of the AANN which is associated to its generalisation capacity is addressed. It will be shown that vibration response data combined with AANNs is a robust and powerful tool, offering novelty detection even when operational and environmental variations are present. The AANN is a method which has not yet been widely used in the structural health monitoring of composite blades.

  20. Fluoxetine, but not sertraline or citalopram, potentiates the locomotor stimulant effect of cocaine: possible pharmacokinetic effects.

    PubMed

    Fletcher, Paul J; Sinyard, Judy; Salsali, Mahnaz; Baker, Glen B

    2004-07-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine enhances some of the behavioural effects of cocaine, including locomotor stimulation. While this effect has often been interpreted as evidence for a serotonergic component to the behavioural effects of cocaine, direct evidence for this hypothesis is lacking. One alternative explanation is that fluoxetine, by inhibiting cytochrome P450 (CYP) enzymes, interferes with the metabolism of cocaine. These experiments were undertaken to: 1) compare the effects of fluoxetine with those of two other SSRIs, sertraline and citalopram, on cocaine-induced locomotor activity, 2) examine the effects of fluoxetine on cocaine-stimulated locomotion in rats depleted of serotonin (5-hydroxytryptamine; 5-HT), and 3) determine the effect of fluoxetine on cocaine levels in the brain. Locomotor activity was measured, using photocell based activity monitors, in rats habituated to those monitors. Depletion of 5-HT was achieved by injecting 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal and median raphe nuclei. Cocaine levels in whole brain were measured using high-performance liquid chromatography with ultraviolet detection. In experiment 1, 5 mg/kg fluoxetine enhanced the ability of 10 and 15 mg/kg cocaine to increase locomotor activity. Neither citalopram nor sertraline (5 and 10 mg/kg) altered the stimulant effect of 10 mg/kg cocaine. Experiment 2 showed that this effect of fluoxetine was also apparent in rats with large and widespread depletion of brain 5-HT levels. The 5-HT depletion also failed to alter the response to cocaine itself. In experiment 3, brain levels of cocaine were elevated in rats pretreated with fluoxetine compared with rats that received cocaine alone. Fluoxetine enhanced the ability of cocaine to increase locomotor activity. This effect appears not to depend upon increasing 5-HT function since fluoxetine was also effective in rats with substantial 5-HT depletions, and two other SSRIs did not alter the

  1. Effects of Varenicline on Ethanol-Induced Conditioned Place Preference, Locomotor Stimulation, and Sensitization

    PubMed Central

    Gubner, Noah R.; McKinnon, Carrie S.; Phillips, Tamara J.

    2014-01-01

    did have effects on locomotor behavior and significantly attenuated acute ethanol-induced locomotor stimulation. In humans who drink while taking varenicline, it might similarly reduce stimulant responses and have an impact on continued drinking. General sedative effects in such individuals should be carefully considered. PMID:25581658

  2. The effects of locomotor-respiratory coupling on the pattern of breathing in horses.

    PubMed Central

    Lafortuna, C L; Reinach, E; Saibene, F

    1996-01-01

    1. To investigate the effect of locomotor activity on the pattern of breathing in quadrupeds, ventilatory response was studied in four healthy horses during horizontal and inclined (7%) treadmill exercise at different velocities (1.4-6.9 m s(-1)) and during chemical stimulation with a rebreathing method. Stride frequency (f(s)) and locomotor-respiratory coupling (LRC) were also simultaneously determined by means of video recordings synchronized with respiratory events. 2. Tidal volume (V(T)) was positively correlated with pulmonary ventilation (V(E)) but significantly different linear regression equations were found between the experimental conditions (P < 0.0001), since the chemical hyperventilation was mainly due to increases in V(T), whereas the major contribution to exercise hyperpnoea came from changes in respiratory frequency (f(R)). 3. The average f(R) at each exercise level was not significantly different from f(S), although there was not always a tight 1:1 LRC. At constant speeds, f(S) was independent of the treadmill slope and hence the greater V(E) during inclined exercise was due to increased V(T). 4. At any ventilatory level, the differences in breathing patterns between locomotion and rebreathing or locomotion at different slopes derived from different set points of the inspiratory off-switch mechanism. 5. The percentage of single breaths entrained with locomotor rhythm rose progressively and significantly with treadmill speed (P < 0.0001) up to a 1:1 LRC and was significantly affected by treadmill slope (P < 0.001). 6. A LRC of 1:1 was systematically observed at canter (10 out of 10 trials) and sometimes at trot (5 out of 14) and it entailed (i) a 4- to 5-fold reduction in both V(T) and f(R) variability, and (ii) a gait-specific phase locking of inspiratory onset during the locomotor cycle. 7. It is concluded that different patterns of breathing are employed during locomotion and rebreathing due to the interference between locomotor and respiratory

  3. Down-Regulation of Decapping Protein 2 Mediates Chronic Nicotine Exposure-Induced Locomotor Hyperactivity in Drosophila

    PubMed Central

    Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

    2012-01-01

    Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence. PMID:23300696

  4. Effects of zacopride and BMY25801 (batanopride) on radiation-induced emesis and locomotor behavior in the ferret

    SciTech Connect

    King, G.L.; Landauer, M.R. )

    1990-06-01

    The antiemetic and locomotor effects of two substituted benzamides, zacopride and batanopride (BMY25801), were compared in ferrets after bilateral 60Co irradiation at 2, 4 or 6 Gy. Both zacopride and BMY25801 were effective against emesis and related signs. Zacopride, tested at several doses (0.003, 0.03 and 0.3 mg/kg), appeared to be more potent because it abolished emesis at 100-fold lower doses than did BMY25801 (3 mg/kg). The ED50 value for the antiemetic effect of zacopride was 0.026 mg/kg (confidence levels = 0.0095, 0.072 mg/kg). However, analysis of emetic parameters recorded from vomiting animals (e.g., latency to first emesis) demonstrated that BMY25801 provided greater antiemetic protection in this population than zacopride without any apparent side effects. Locomotor activity was significantly depressed by both radiation (all doses) and zacopride alone (0.03 mg/kg and 0.3 mg/kg). BMY25801 alone did not affect locomotor activity, and protected against the radiation-induced locomotor decrement. Although zacopride potentiated the locomotor decrement to radiation, no clear dose-response relationship was evident. Bilateral abdominal vagotomy significantly increased the latency to the first emetic episode and significantly reduced the number of retches, but did not alter the duration of the prodromal response to 4-Gy irradiation. Unilateral vagotomies had no effect. Zacopride (at 0.03 mg/kg and 0.3 mg/kg) remained an effective antiemetic in animals that received a bilateral vagotomy, abolishing emesis in four of eight and two of eight ferrets, respectively. These data suggest that the antiemetic action of zacopride does not fully depend on intact vagal innervation and also acts via other pathways.

  5. Down-regulation of Decapping Protein 2 mediates chronic nicotine exposure-induced locomotor hyperactivity in Drosophila.

    PubMed

    Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

    2012-01-01

    Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence.

  6. Nitric oxide-mediated modulation of the murine locomotor network.

    PubMed

    Foster, Joshua D; Dunford, Catherine; Sillar, Keith T; Miles, Gareth B

    2014-02-01

    Spinal motor control networks are regulated by neuromodulatory systems to allow adaptability of movements. The present study aimed to elucidate the role of nitric oxide (NO) in the modulation of mammalian spinal locomotor networks. This was investigated with isolated spinal cord preparations from neonatal mice in which rhythmic locomotor-related activity was induced pharmacologically. Bath application of the NO donor diethylamine NONOate (DEA/NO) decreased the frequency and modulated the amplitude of locomotor-related activity recorded from ventral roots. Removal of endogenous NO with coapplication of a NO scavenger (PTIO) and a nitric oxide synthase (NOS) blocker [nitro-l-arginine methyl ester (l-NAME)] increased the frequency and decreased the amplitude of locomotor-related activity. This demonstrates that endogenously derived NO can modulate both the timing and intensity of locomotor-related activity. The effects of DEA/NO were mimicked by the cGMP analog 8-bromo-cGMP. In addition, the soluble guanylyl cyclase (sGC) inhibitor ODQ blocked the effects of DEA/NO on burst amplitude and frequency, although the frequency effect was only blocked at low concentrations of DEA/NO. This suggests that NO-mediated modulation involves cGMP-dependent pathways. Sources of NO were studied within the lumbar spinal cord during postnatal development (postnatal days 1-12) with NADPH-diaphorase staining. NOS-positive cells in the ventral horn exhibited a rostrocaudal gradient, with more cells in rostral segments. The number of NOS-positive cells was also found to increase during postnatal development. In summary, we have shown that NO, derived from sources within the mammalian spinal cord, modulates the output of spinal motor networks and is therefore likely to contribute to the fine-tuning of locomotor behavior.

  7. Genotypic structure of a Drosophila population for adult locomotor activity

    SciTech Connect

    Grechanyi, G.V.; Korzun, V.M.

    1995-01-01

    Analysis of the variation of adult locomotor activity in four samples taken at different times from a natural population of Drosophila melanogaster showed that the total variation of this trait is relatively stable in time and has a substantial genetic component. Genotypic structure of the population for locomotor activity is characterized by the presence of large groups of genotypes with high and low values of this trait. A possible explanation for the presence of such groups in a population is cyclic density-dependent selection.

  8. How Transcription Networks Evolve and Produce Biological Novelty.

    PubMed

    Nocedal, Isabel; Johnson, Alexander D

    2015-01-01

    The rewiring of gene regulatory networks over evolutionary timescales produces changes in the patterns of gene expression and is a major source of diversity among species. Yet the molecular mechanisms underlying evolutionary rewiring are only beginning to be understood. Here, we discuss recent analyses in ascomycete yeasts that have revealed several general principles of network rewiring. Specifically, we discuss how transcription networks can maintain a functional output despite changes in mechanism, how specific types of constraints alter available evolutionary trajectories, and how regulatory rewiring can ultimately lead to phenotypic novelty. We also argue that the structure and "logic" of extant gene regulatory networks can largely be accounted for by constraints that shape their evolutionary trajectories. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  9. Singular value decomposition for novelty detection in ultrasonic pipe monitoring

    NASA Astrophysics Data System (ADS)

    Liu, Chang; Harley, Joel B.; Ying, Yujie; Oppenheim, Irving J.; Bergés, Mario; Greve, David W.; Garrett, James H.

    2013-04-01

    Guided wave ultrasonics is an attractive technique for structural health monitoring, especially on pressurized pipes. However, civil infrastructure components, including pipes, are often subject to large environmental and operational variations that prevent traditional baseline subtraction-based approaches from detecting damage. We collect ultrasonic data on a large-scale pipe segment in its normal operating conditions and observe large environmental variations. We developed a damage detection method based on singular value decomposition (SVD) that is robust to those benign variations. We further develop an online novelty detection framework based on our SVD method to detect the presence of a mass scatterer on the pipe at the same time that we collect the data. We examine the framework with both synthetic simulations and field experimental data. The results show that the framework can effectively detect the presence of a scatterer and is robust to large environmental and operational variations.

  10. Novelty and conflict in the categorization of complex stimuli

    PubMed Central

    FOLSTEIN, JONATHAN R.; VAN PETTEN, CYMA; ROSE, SCOTT A.

    2008-01-01

    We manipulated categorical typicality and the presence of conflicting information as participants categorized multifeatured artificial animals. In Experiment 1, rule-irrelevant features were correlated with particular categories during training. In the test phase, participants applied a one-dimensional rule to stimuli with rule-irrelevant features that were category-congruent, category-incongruent, or novel. Category-incongruent and novel features delayed RT and P3 latency, but had no effect on the N2. Experiment 2 used a two-dimensional rule to create conflict between rule-relevant features. Conflict resulted in prolonged RTs and larger amplitudes of a prefrontal positive component, but had no impact on the N2. Stimuli with novel features did elicit a larger N2 than those with frequent features. These results suggest limitations on the generality of the N2′s sensitivity to conflicting information while confirming its sensitivity to attended visual novelty. PMID:18047482

  11. Chemical Structural Novelty: On-Targets and Off-Targets

    PubMed Central

    Yera, Emmanuel R.; Cleves, Ann. E.; Jain, Ajay N.

    2011-01-01

    Drug structures may be quantitatively compared based on 2D topological structural considerations and based on 3D characteristics directly related to binding. A framework for combining multiple similarity computations is presented along with its systematic application to 358 drugs with overlapping pharmacology. Given a new molecule along with a set of molecules sharing some biological effect, a single score based on comparison to the known set is produced, reflecting either 2D similarity, 3D similarity, or their combination. For prediction of primary targets, the benefit of 3D over 2D was relatively small, but for prediction of off-targets, the added benefit was large. In addition to assessing prediction, the relationship between chemical similarity and pharmacological novelty was studied. Drug pairs that shared high 3D similarity but low 2D similarity (i.e. a novel scaffold) were shown to be much more likely to exhibit pharmacologically relevant differences in terms of specific protein target modulation. PMID:21916467

  12. Cadherin genes and evolutionary novelties in the octopus.

    PubMed

    Wang, Z Yan; Ragsdale, Clifton W

    2017-09-01

    All animals with large brains must have molecular mechanisms to regulate neuronal process outgrowth and prevent neurite self-entanglement. In vertebrates, two major gene families implicated in these mechanisms are the clustered protocadherins and the atypical cadherins. However, the molecular mechanisms utilized in complex invertebrate brains, such as those of the cephalopods, remain largely unknown. Recently, we identified protocadherins and atypical cadherins in the octopus. The octopus protocadherin expansion shares features with the mammalian clustered protocadherins, including enrichment in neural tissues, clustered head-to-tail orientations in the genome, and a large first exon encoding all cadherin domains. Other octopus cadherins, including a newly-identified cadherin with 77 extracellular cadherin domains, are elevated in the suckers, a striking cephalopod novelty. Future study of these octopus genes may yield insights into the general functions of protocadherins in neural wiring and cadherin-related proteins in complex morphogenesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Control of locomotor stability in stabilizing and destabilizing environments.

    PubMed

    Wu, Mengnan/Mary; Brown, Geoffrey; Gordon, Keith E

    2017-06-01

    To develop effective interventions targeting locomotor stability, it is crucial to understand how people control and modify gait in response to changes in stabilization requirements. Our purpose was to examine how individuals with and without incomplete spinal cord injury (iSCI) control lateral stability in haptic walking environments that increase or decrease stabilization demands. We hypothesized that people would adapt to walking in a predictable, stabilizing viscous force field and unpredictable destabilizing force field by increasing and decreasing feedforward control of lateral stability, respectively. Adaptations in feedforward control were measured using after-effects when fields were removed. Both groups significantly (p<0.05) decreased step width in the stabilizing field. When the stabilizing field was removed, narrower steps persisted in both groups and subjects with iSCI significantly increased movement variability (p<0.05). The after-effect of walking in the stabilizing field was a suppression of ongoing general stabilization mechanisms. In the destabilizing field, subjects with iSCI took faster steps and increased lateral margins of stability (p<0.05). Step frequency increases persisted when the destabilizing field was removed (p<0.05), suggesting that subjects with iSCI made feedforward adaptions to increase control of lateral stability. In contrast, in the destabilizing field, non-impaired subjects increased movement variability (p<0.05) and did not change step width, step frequency, or lateral margin of stability (p>0.05). When the destabilizing field was removed, increases in movement variability persisted (p<0.05), suggesting that non-impaired subjects made feedforward decreases in resistance to perturbations. Published by Elsevier B.V.

  14. Liquid crystal TV-based white light optical tracking novelty filter.

    PubMed

    Li, Y; Kostrzewski, A; Kim, D H; Eichmann, G

    1989-11-15

    A compact white light optical tracking novelty filter is demonstrated. Based on the use of two inexpensive liquid crystal televisions, a filtered and collimated white light source, digital delay, and video recorder, this portable white light device performs two major image comparison operations, a real time image subtraction and novelty tracking operations. Some preliminary experimental results are presented.

  15. Predatory Odor Disrupts Social Novelty Preference in Long-Evans Rats

    ERIC Educational Resources Information Center

    Anderson, Matthew J.; Layton, William B.

    2012-01-01

    The present study examined the effects of predatory odor (cat urine) on social novelty preference in Long-Evans rats. Adult male subjects encountered a juvenile conspecific at training, were exposed to either clean cat litter (control) or litter soiled with cat urine (predatory odor), and were tested for social novelty preference. While the…

  16. The time course of novelty processing in sensation seeking: an ERP study.

    PubMed

    Zheng, Ya; Xu, Jing; Jin, Yuan; Sheng, Wenbin; Ma, Ying; Zhang, Xiaoyu; Shen, Huijuan

    2010-05-01

    Novelty processing is critical for human survival in a rapidly changing environment. However, how and when the orientation attention reflected by novelty processing is modulated by personality elements such as sensation seeking is still opened. The present study investigated the time course of novelty processing in sensation seeking by recording the event-related potentials (ERPs) in a visual novelty oddball task. High and low sensation seekers performed a visual oddball task, in which participants were instructed to detect an inverted triangle (target) and ignore both upright triangle (standard) and unrepeated line drawings of pseudo-objects deviant from participants' long-term memory (novelty). While there were no group differences in ERPs to standard and target stimuli, ERPs to novel stimuli showed a strong modulation by sensation seeking trait. The low sensation seekers, compared with the high sensation seekers, exhibited an increased N2 to novel stimuli at frontal sites. Moreover, the Pd3 component reflecting purely novelty processing was enhanced and less habituated in the high sensation seeking participants. The current findings implicated that low sensation seekers showed sensitivity to novelty detection, whereas high sensation seekers displayed stronger and more sustained novelty appraisal.

  17. Effects of caffeine and L-phenylisopropyladenosine on locomotor activity of mice

    SciTech Connect

    Buckholtz, N.S.; Middaugh, L.D.

    1987-10-01

    C57BL/6J and DBA/2J mice were used to determine if possible differences in the behavioral response to caffeine might be related to differences in A1 adenosine receptors. Caffeine stimulated locomotor activity of both strains, but the dose-response relationship and time course of drug action differed according to strain. Although their response to caffeine differed, the strains did not differ in response to the A1 adenosine agonist L-phenylisopropyladenosine (PIA) nor in the binding of the A1 agonist (/sup 3/H)N6-cyclohexyladenosine (CHA) in various brain regions. Thus, the behavioral differences in response to caffeine could not be accounted for by differences in adenosine binding. Of alternative mechanisms, strain differences in A2 receptors appear to be the most promising.

  18. Linking the evolution of body shape and locomotor biomechanics in bird-line archosaurs.

    PubMed

    Allen, Vivian; Bates, Karl T; Li, Zhiheng; Hutchinson, John R

    2013-05-02

    Locomotion in living birds (Neornithes) has two remarkable features: feather-assisted flight, and the use of unusually crouched hindlimbs for bipedal support and movement. When and how these defining functional traits evolved remains controversial. However, the advent of computer modelling approaches and the discoveries of exceptionally preserved key specimens now make it possible to use quantitative data on whole-body morphology to address the biomechanics underlying this issue. Here we use digital body reconstructions to quantify evolutionary trends in locomotor biomechanics (whole-body proportions and centre-of-mass position) across the clade Archosauria. We use three-dimensional digital reconstruction to estimate body shape from skeletal dimensions for 17 archosaurs along the ancestral bird line, including the exceptionally preserved, feathered taxa Microraptor, Archaeopteryx, Pengornis and Yixianornis, which represent key stages in the evolution of the avian body plan. Rather than a discrete transition from more-upright postures in the basal-most birds (Avialae) and their immediate outgroup deinonychosauria, our results support hypotheses of a gradual, stepwise acquisition of more-crouched limb postures across much of theropod evolution, although we find evidence of an accelerated change within the clade Maniraptora (birds and their closest relatives, such as deinonychosaurs). In addition, whereas reduction of the tail is widely accepted to be the primary morphological factor correlated with centre-of-mass position and, hence, evolution of hindlimb posture, we instead find that enlargement of the pectoral limb and several associated trends have a much stronger influence. Intriguingly, our support for the onset of accelerated morpho-functional trends within Maniraptora is closely correlated with the evolution of flight. Because we find that the evolution of enlarged forelimbs is strongly linked, via whole-body centre of mass, to hindlimb function during

  19. Relationship between parameters of bacteriorhodopsin film and behavior of optical novelty filters.

    PubMed

    Chen, Guiying; Zhang, Chunping; Guo, Zongxia; Xu, Tang; Liang, Xin; Wang, Xinyu; Tian, Jianguo; Song, Q Wang

    2005-10-20

    To continue our earlier research on novelty filters in a system of incoherent light [Opt. Lett. 30,81 (2005)], we discuss the relationship between parameters of a bacteriorhodopsin film and the quality of a novelty filter image. For both fixed and moving velocities of the input image, differences in the novelty filter's image as a function of thickness, lifetime of the M state, and molecular concentration are displayed, and the optimal ranges of parameters of the bR film that correspond to the entire novelty filter image and obvious gray-level differences in the image are given. The method can be used to design high-quality novelty filter images in incoherent light systems.

  20. Product design and apparent usability. The influence of novelty in product appearance.

    PubMed

    Mugge, Ruth; Schoormans, Jan P L

    2012-11-01

    This research enhances our understanding of the relationship between aesthetics and usability by investigating the effects of novelty in product appearance on the apparent usability of a product. In two experimental studies using washing machines and digital cameras as stimuli, we systematically manipulated the level of novelty (low vs. high) in the product appearance by changing the product's color or shape. Participants were presented with one of these product appearances and a list of the product's technical specifications. Next, participants indicated how difficult or easy they expected the usage of the product to be. Our findings demonstrate that because people associate a high level of novelty with technological advancement, novelty in a product appearance negatively affects their expectations of a product's usability at the point of sale. Furthermore, novices are more likely to use the level of novelty as a cue for a product's apparent usability than experts.

  1. Neonatal olfactory bulbectomy enhances locomotor activity, exploratory behavior and binding of NMDA receptors in pre-pubertal rats.

    PubMed

    Flores, G; Ibañez-Sandoval, O; Silva-Gómez, A B; Camacho-Abrego, I; Rodríguez-Moreno, A; Morales-Medina, J C

    2014-02-14

    In this study, we investigated the effect of neonatal olfactory bulbectomy (nOBX) on behavioral paradigms related to olfaction such as exploratory behavior, locomotor activity in a novel environment and social interaction. We also studied the effect of nOBX on the activity of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors during development. The behavioral effects of nOBX (postnatal day 7, PD7) were investigated in pre- (PD30) and post-pubertal (PD60) Wistar rats. NMDA receptor activity was measured with [(125)I]MK-801 in the brain regions associated with the olfactory circuitry. A significant increase in the novelty-induced locomotion was seen in the pre-pubertal nOBX rats. Although the locomotor effect was less marked than in pre-pubertal rats, the nOBX rats tested post-pubertally failed to habituate to the novel situation as quickly as the sham- and normal- controls. Pre-pubertally, the head-dipping behavior was enhanced in nOBX rats compared with sham-operated and normal controls, while normal exploratory behavior was observed between groups in adulthood. In contrast, social interaction was increased in post-pubertal animals that underwent nOBX. Both pre- and post-pubertal nOBX rats recovered olfaction. Interestingly, pre-pubertal rats showed a significant increase in the [(125)I]MK-801 binding in the piriform cortex, dorsal hippocampus, inner and outer layers of the frontal cortex and outer layer of the cingulate cortex. At post-pubertal age, no significant differences in [(125)I]MK-801 binding were observed between groups at any of the brain regions analyzed. These results suggest that nOBX produces pre-pubertal behavioral disturbances and NMDA receptor changes that are transitory with recovery of olfaction early in adulthood.

  2. Spatial learning impairment induced by chronic stress is related to individual differences in novelty reactivity: search for neurobiological correlates.

    PubMed

    Touyarot, K; Venero, C; Sandi, C

    2004-02-01

    Although chronic stress has been reported to induce deleterious effects on hippocampal structure and function, the possible existence of individual differences in the vulnerability to develop stress-induced cognitive alterations was hypothesized. This study was designed to evaluate (i) whether individual variability in behavioural reactivity to novelty could be related to a differential vulnerability to show spatial learning deficits after chronic stress in young adult rats, and (ii) to what extent, could individual differences in stress-induced cognitive alterations be related to alterations in specific neurobiological substrates. Four month-old Wistar male rats were classified according to their locomotor reactivity to a novel environment, as either low (LR) or highly (HR) reactive, and then either submitted to psychosocial stress for 21-days (consisting of the daily cohabitation of each young adult rat with a new middle-aged rat) or left undisturbed. The results showed that psychosocial stress induced a marked deficit in spatial learning in the water maze in HR, but not in LR, rats. Then, a second experiment investigated the possible differential expression of corticosteroid receptors (MR and GR) and cell adhesion molecules (NCAM and L1) in the hippocampus of HR and LR rats, both under basal conditions and after exposure to chronic social stress. Although chronic stress induced a reduction on the hippocampal expression of MRs and the NCAM-140 isoform, the levels of these molecules did not differ between stressed rats with and without spatial learning impairments; i.e., between HR- and LR-stressed rats, respectively. Nevertheless, it should be noted that the reduction of the hippocampal expression of NCAM-140 induced by psychosocial stress was particularly marked in HR stressed rats. However, the expression of GRs, NCAM-120 and NCAM-180 isoforms, and L1, was not affected by stress, regardless of the reactivity of the animals. Therefore, although we failed to find

  3. Dynamic "Range of Motion" Hindlimb Stretching Disrupts Locomotor Function in Rats with Moderate Subacute Spinal Cord Injuries.

    PubMed

    Keller, Anastasia; Rees, Kathlene; Prince, Daniella; Morehouse, Johnny; Shum-Siu, Alice; Magnuson, David

    2017-04-12

    Joint contractures and spasticity are two common secondary complications of a severe spinal cord injury (SCI), which can significantly reduce quality of life, and stretching is one of the top strategies for rehabilitation of these complications. We have previously shown that a daily static stretching protocol administered to rats at either acute or chronic time points after a moderate or moderate-severe T10 SCI significantly disrupts their hindlimb locomotor function. The objective of the current study was to examine the effects of dynamic range of motion (ROM) stretching on the locomotor function of rats with SCI as an alternative to static stretching. Starting at 6 weeks post-injury (T10 moderate contusion) eight adult Sprague-Dawley rats were subjected to hindlimb stretching for 4 weeks. Our standard stretching protocol (six maneuvers to stretch the major hindlimb muscle groups) was modified from 1 min static stretch-and-hold at the end ROM of each stretch position to a dynamic 2 sec hold, 1 sec release rhythm repeated for a duration of 1 min. Four weeks of daily (5 days/week) dynamic stretching led to significant disruption of locomotor function as assessed by the Basso, Beattie, Bresnahan (BBB) Open Field Locomotor Scale and three-dimensional (3D) kinematic and gait analyses. In addition, we identified and analyzed an apparently novel hindlimb response to dynamic stretch that resembles human clonus. The results of the current study extend the observation of the stretching phenomenon to a new modality of stretching that is also commonly used in SCI rehabilitation. Although mechanisms and clinical relevance still need to be established, our findings continue to raise concerns that stretching as a therapy can potentially hinder aspects of locomotor recovery.

  4. Effects of exogenous corticosterone on locomotor activity in the red-eared slider turtle, Trachemys scripta elegans.

    PubMed

    Cash, W B; Holberton, R L

    1999-11-01

    We investigated the effects of exogenous corticosterone on the locomotor activity of captive red-eared slider turtles, Trachemys scripta elegans. An increase in plasma corticosterone often increases locomotor activity in mammals and birds, but there are no reported findings for turtles. In this study turtles implanted with corticosterone-filled Silastic((R)) implants showed a significant increase in caged locomotor activity when compared to control animals with empty implants. Corticosterone-treated turtles also showed a significant increase in plasma corticosterone concentration when pre-trial plasma samples were compared to post-trial plasma samples, while control turtles exhibited no such increase, validating the effectiveness of our implants to deliver corticosterone. Although corticosterone remained high at the end of the activity trials, the increase in activity was ephemeral in nature, peaking within 48 hr after the implant was in place. This suggests that the effects of corticosterone on behavior may be context-dependent (i.e., whether the turtles can find food) and concentration-dependent, and that there are underlying physiological mechanisms, perhaps mediated at the receptor level in the brain, involved in locomotor activity behavior in slider turtles. Environmental perturbations that cause a reduction in available food resources may cause the organism to increase its level of locomotor activity to increase food encounter rate but later reduce activity to conserve energy reserves. These data are important when considering behavioral and physiological mechanisms involved in a turtle's response to changing conditions in habitat quality. J. Exp. Zool. 284:637-644, 1999. Copyright 1999 Wiley-Liss, Inc.

  5. A Model of Locomotor-Respiratory Coupling in Quadrupeds

    ERIC Educational Resources Information Center

    Giuliodori,, Mauricio J.; Lujan, Heidi L.; Briggs, Whitney S.; DiCarlo, Stephen E.

    2009-01-01

    Locomotion and respiration are not independent phenomena in running mammals because locomotion and respiration both rely on cyclic movements of the ribs, sternum, and associated musculature. Thus, constraints are imposed on locomotor and respiratory function by virtue of their linkage. Specifically, locomotion imposes mechanical constraints on…

  6. Active Gaze, Visual Look-Ahead, and Locomotor Control

    ERIC Educational Resources Information Center

    Wilkie, Richard M.; Wann, John P.; Allison, Robert S.

    2008-01-01

    The authors examined observers steering through a series of obstacles to determine the role of active gaze in shaping locomotor trajectories. Participants sat on a bicycle trainer integrated with a large field-of-view simulator and steered through a series of slalom gates. Steering behavior was determined by examining the passing distance through…

  7. Locomotor Sub-functions for Control of Assistive Wearable Robots.

    PubMed

    Sharbafi, Maziar A; Seyfarth, Andre; Zhao, Guoping

    2017-01-01

    A primary goal of comparative biomechanics is to understand the fundamental physics of locomotion within an evolutionary context. Such an understanding of legged locomotion results in a transition from copying nature to borrowing strategies for interacting with the physical world regarding design and control of bio-inspired legged robots or robotic assistive devices. Inspired from nature, legged locomotion can be composed of three locomotor sub-functions, which are intrinsically interrelated: Stance: redirecting the center of mass by exerting forces on the ground. Swing: cycling the legs between ground contacts. Balance: maintaining body posture. With these three sub-functions, one can understand, design and control legged locomotory systems with formulating them in simpler separated tasks. Coordination between locomotor sub-functions in a harmonized manner appears then as an additional problem when considering legged locomotion. However, biological locomotion shows that appropriate design and control of each sub-function simplifies coordination. It means that only limited exchange of sensory information between the different locomotor sub-function controllers is required enabling the envisioned modular architecture of the locomotion control system. In this paper, we present different studies on implementing different locomotor sub-function controllers on models, robots, and an exoskeleton in addition to demonstrating their abilities in explaining humans' control strategies.

  8. Unraveling a locomotor network, many neurons at a time.

    PubMed

    Brownstone, Robert M; Stifani, Nicolas

    2015-04-08

    In this issue of Neuron, Bruno et al. (2015) use large-scale recordings in Aplysia, and apply novel dimensionality-reduction techniques to define dynamical building blocks involved in locomotor behavior. These techniques open new avenues to the study of neuronal networks.

  9. A Model of Locomotor-Respiratory Coupling in Quadrupeds

    ERIC Educational Resources Information Center

    Giuliodori,, Mauricio J.; Lujan, Heidi L.; Briggs, Whitney S.; DiCarlo, Stephen E.

    2009-01-01

    Locomotion and respiration are not independent phenomena in running mammals because locomotion and respiration both rely on cyclic movements of the ribs, sternum, and associated musculature. Thus, constraints are imposed on locomotor and respiratory function by virtue of their linkage. Specifically, locomotion imposes mechanical constraints on…

  10. Diagnostic imaging of the locomotor system- historical reviev.

    PubMed

    Swiatkowski, Jan; Białoszewski, Dariusz; Urbanik, Andrzej

    2002-10-30

    This work discusses the stages in the development of techniques used for imaging the locomotor apparatus. Attention is also drawn to the fact that from the very beginning of the "Roentgen era" Polish scientists were among its leading advocates and promoters.

  11. Active Gaze, Visual Look-Ahead, and Locomotor Control

    ERIC Educational Resources Information Center

    Wilkie, Richard M.; Wann, John P.; Allison, Robert S.

    2008-01-01

    The authors examined observers steering through a series of obstacles to determine the role of active gaze in shaping locomotor trajectories. Participants sat on a bicycle trainer integrated with a large field-of-view simulator and steered through a series of slalom gates. Steering behavior was determined by examining the passing distance through…

  12. Nature and Causes of Locomotor Disabilities in India

    ERIC Educational Resources Information Center

    Halder, Santoshi; Talukdar, Arindam

    2013-01-01

    A large proportion of disability around the world is preventable. Levels of disability in many poor countries can be reduced by achieving the international development targets for economic, social and human development. In this paper, the author studied the different contributory and causative factors of locomotor disability, disease states and…

  13. Locomotor Sub-functions for Control of Assistive Wearable Robots

    PubMed Central

    Sharbafi, Maziar A.; Seyfarth, Andre; Zhao, Guoping

    2017-01-01

    A primary goal of comparative biomechanics is to understand the fundamental physics of locomotion within an evolutionary context. Such an understanding of legged locomotion results in a transition from copying nature to borrowing strategies for interacting with the physical world regarding design and control of bio-inspired legged robots or robotic assistive devices. Inspired from nature, legged locomotion can be composed of three locomotor sub-functions, which are intrinsically interrelated: Stance: redirecting the center of mass by exerting forces on the ground. Swing: cycling the legs between ground contacts. Balance: maintaining body posture. With these three sub-functions, one can understand, design and control legged locomotory systems with formulating them in simpler separated tasks. Coordination between locomotor sub-functions in a harmonized manner appears then as an additional problem when considering legged locomotion. However, biological locomotion shows that appropriate design and control of each sub-function simplifies coordination. It means that only limited exchange of sensory information between the different locomotor sub-function controllers is required enabling the envisioned modular architecture of the locomotion control system. In this paper, we present different studies on implementing different locomotor sub-function controllers on models, robots, and an exoskeleton in addition to demonstrating their abilities in explaining humans' control strategies. PMID:28928650

  14. Acute Neuroactive Drug Exposures alter Locomotor Activity in Larval Zebrafish

    EPA Science Inventory

    As part of the development of a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae by assessing the acute effects of prototypic drugs that act on the central nervous system. Initially,...

  15. Acute Neuroactive Drug Exposures alter Locomotor Activity in Larval Zebrafish

    EPA Science Inventory

    As part of the development of a rapid in vivo screen for prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae by assessing the acute effects of prototypic drugs that act on the central nervous system. Initially,...

  16. DRUG EFFECTS ON THE LOCOMOTOR ACTIVITY OF LARVAL ZEBRAFISH.

    EPA Science Inventory

    As part of an effort to develop a rapid in vivo screen for EPA’s prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae and the effects of prototype drugs. Zebrafish larvae (6-7 days post-fertilization) were indiv...

  17. Locomotor Experience and Use of Social Information Are Posture Specific

    ERIC Educational Resources Information Center

    Adolph, Karen E.; Tamis-LeMonda, Catherine S.; Ishak, Shaziela; Karasik, Lana B.; Lobo, Sharon A.

    2008-01-01

    The authors examined the effects of locomotor experience on infants' perceptual judgments in a potentially risky situation--descending steep and shallow slopes--while manipulating social incentives to determine where perceptual judgments are most malleable. Twelve-month-old experienced crawlers and novice walkers were tested on an adjustable…

  18. Limits to human locomotor performance: phylogenetic origins and comparative perspectives.

    PubMed

    Dudley, R

    2001-09-01

    Studies of human exercise physiology have been conducted from a largely ahistorical perspective. This approach usefully elucidates proximate limits to locomotor performance, but ignores potential sources of biomechanical and physiological variation that derive from adaptation to ancestral environments. Phylogenetic reconstruction suggests that multiple hominoid lineages, including that leading to Homo sapiens, evolved in African highlands at altitudes of 1000-2000 m. The evolution of human locomotor physiology therefore occurred under conditions of hypobaric hypoxia. In contrast to present-day humans running on treadmills or exercising in otherwise rectilinear trajectories, ancestral patterns of hominid locomotion probably involved intermittent knuckle-walking over variable terrain, occasional bouts of arboreality and an evolving capacity for bipedalism. All such factors represent potential axes of locomotor variation at present unstudied in extant hominoid taxa. As with humans, hummingbirds evolved in mid-montane contexts but pose an extreme contrast with respect to body size, locomotor mode and metabolic capacity. Substantial biomechanical and physiological challenges are associated with flight in hypobaria. Nonetheless, hummingbird lineages demonstrate a progressive invasion of higher elevations and a remarkable tolerance to hypoxia during hovering. Upregulation of aerobic capacity and parallel resistance to hypoxia may represent coupled evolutionary adaptations to flight under high-altitude conditions.

  19. DRUG EFFECTS ON THE LOCOMOTOR ACTIVITY OF LARVAL ZEBRAFISH.

    EPA Science Inventory

    As part of an effort to develop a rapid in vivo screen for EPA’s prioritization of toxic chemicals, we have begun to characterize the locomotor activity of zebrafish (Danio rerio) larvae and the effects of prototype drugs. Zebrafish larvae (6-7 days post-fertilization) were indiv...

  20. Acute neuroactive drug exposures alter locomotor activity in larval zebrafish

    EPA Science Inventory

    In an effort to develop a rapid in vivo screen for EPA's prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after exposure to prototypic drugs that act on the central nervous system. MPTP (1-methyl-4phenyl- 1 ,2,3,6-...

  1. Acute neuroactive drug exposures alter locomotor activity in larval zebrafish

    EPA Science Inventory

    In an effort to develop a rapid in vivo screen for EPA's prioritization of toxic chemicals, we are characterizing the locomotor activity of zebrafish (Danio rerio) larvae after exposure to prototypic drugs that act on the central nervous system. MPTP (1-methyl-4phenyl- 1 ,2,3,6-...

  2. Effects of a selective Y2R antagonist, JNJ-31020028, on nicotine abstinence-related social anxiety-like behavior, neuropeptide Y and corticotropin releasing factor mRNA levels in the novelty-seeking phenotype

    PubMed Central

    Aydin, Cigdem; Oztan, Ozge; Isgor, Ceylan

    2011-01-01

    An outbred rat model of novelty-seeking phenotype has predictive value for the expression of locomotor sensitization to nicotine. When experimentally naïve rats are exposed to a novel environment, some display high rates of locomotor reactivity (HRs, scores ranking at top 1/3rd of the population), whereas some display low rates (LRs, scores ranking at bottom 1/3rd of the population). Basally, HRs display lower anxiety-like behavior compared to LRs along with higher neuropeptide Y (NPY) mRNA in the amygdala and the hippocampus. Following an intermittent behavioral sensitization to nicotine regimen and 1 wk of abstinence, HRs show increased social anxiety-like behavior in the social interaction test and robust expression of locomotor sensitization to a low dose nicotine challenge. These effects are accompanied by a deficit in NPY mRNA levels in the medial nucleus of the amygdala and the CA3 field of the hippocampus, and increases in Y2R mRNA levels in the CA3 field and corticotropin releasing factor (CRF) mRNA levels in the central nucleus of the amygdala. Systemic and daily injections of a Y2R antagonist, JNJ-31020028, during abstinence fully reverse nicotine-induced social anxiety-like behavior, the expression of locomotor sensitization to nicotine challenge, the deficit in the NPY mRNA levels in the amygdala and the hippocampus, as well as result an increase in Y2R mRNA levels in the hippocampus and the CRF mRNA levels in the amygdala in HRs. These findings implicate central Y2R in neuropeptidergic regulation of social anxiety in a behavioral sensitization to nicotine regimen in the LRHR rats. PMID:21497168

  3. Influence of benzodiazepine tranquilizers on scopolamine-induced locomotor stimulation in mice.

    PubMed

    Sansone, M

    1980-01-01

    Four benzodiazepine tranquilizers have been tested, alone or in combination with scopolamine, on the spontaneous locomotor activity of BALB/c mice. Scopolamine-induced locomotor stimulation was enhanced by chlordiazepoxide, diazepam, and medazepam, but not by bromazepam. These effects are similar to those exerted by the four benzodiazepines on amphetamine-induced locomotor stimulation and allow the same differentiation between the four derivatives.

  4. Activation of Neurotensin Receptor Type 1 Attenuates Locomotor Activity

    PubMed Central

    Vadnie, Chelsea A.; Hinton, David J.; Choi, Sun; Choi, YuBin; Ruby, Christina L.; Oliveros, Alfredo; Prieto, Miguel L.; Park, Jun Hyun; Choi, Doo-Sup

    2014-01-01

    Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity. Systemic administration of PD149163 attenuated the locomotor activity of C57BL/6J mice both in a novel environment and in their homecage. However, mice developed tolerance to the hypolocomotor effect of PD149163 (0.1 mg/kg, i.p.). Since NTS1 is known to modulate dopaminergic signaling, we examined whether PD149163 blocks dopamine receptor-mediated hyperactivity. Pretreatment with PD149163 (0.1 or 0.05 mg/kg, i.p.) inhibited D2R agonist bromocriptine (8 mg/kg, i.p.)-mediated hyperactivity. D1R agonist SKF81297 (8 mg/kg, i.p.)-induced hyperlocomotion was only inhibited by 0.1 mg/kg of PD149163. Since the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) have been implicated in the behavioral effects of NT, we examined whether microinjection of PD149163 into these regions reduces locomotion. Microinjection of PD149163 (2 pmol) into the NAc, but not the mPFC suppressed locomotor activity. In summary, our results indicate that systemic and intra-NAc activation of NTS1 is sufficient to reduce locomotion and NTS1 activation inhibits D2R-mediated hyperactivity. Our study will be helpful to identify pharmacological factors and a possible therapeutic window for NTS1-targeted therapies for movement disorders. PMID:24929110

  5. Interpreting locomotor biomechanics from the morphology of human footprints.

    PubMed

    Hatala, Kevin G; Wunderlich, Roshna E; Dingwall, Heather L; Richmond, Brian G

    2016-01-01

    Fossil hominin footprints offer unique direct windows to the locomotor behaviors of our ancestors. These data could allow a clearer understanding of the evolution of human locomotion by circumventing issues associated with indirect interpretations of habitual locomotor patterns from fossil skeletal material. However, before we can use fossil hominin footprints to understand better the evolution of human locomotion, we must first develop an understanding of how locomotor biomechanics are preserved in, and can be inferred from, footprint morphologies. In this experimental study, 41 habitually barefoot modern humans created footprints under controlled conditions in which variables related to locomotor biomechanics could be quantified. Measurements of regional topography (depth) were taken from 3D models of those footprints, and principal components analysis was used to identify orthogonal axes that described the largest proportions of topographic variance within the human experimental sample. Linear mixed effects models were used to quantify the influences of biomechanical variables on the first five principal axes of footprint topographic variation, thus providing new information on the biomechanical variables most evidently expressed in the morphology of human footprints. The footprint's overall depth was considered as a confounding variable, since biomechanics may be linked to the extent to which a substrate deforms. Three of five axes showed statistically significant relationships with variables related to both locomotor biomechanics and substrate displacement; one axis was influenced only by biomechanics and another only by the overall depth of the footprint. Principal axes of footprint morphological variation were significantly related to gait type (walking or running), kinematics of the hip and ankle joints and the distribution of pressure beneath the foot. These results provide the first quantitative framework for developing hypotheses regarding the

  6. The ventromedial hypothalamus oxytocin induces locomotor behavior regulated by estrogen.

    PubMed

    Narita, Kazumi; Murata, Takuya; Matsuoka, Satoshi

    2016-10-01

    Our previous studies demonstrated that excitation of neurons in the rat ventromedial hypothalamus (VMH) induced locomotor activity. An oxytocin receptor (Oxtr) exists in the VMH and plays a role in regulating sexual behavior. However, the role of Oxtr in the VMH in locomotor activity is not clear. In this study we examined the roles of oxytocin in the VMH in running behavior, and also investigated the involvement of estrogen in this behavioral change. Microinjection of oxytocin into the VMH induced a dose-dependent increase in the running behavior in male rats. The oxytocin-induced running activity was inhibited by simultaneous injection of Oxtr-antagonist, (d(CH2)5(1), Try(Me)(2), Orn(8))-oxytocin. Oxytocin injection also induced running behavior in ovariectomized (OVX) female rats. Pretreatment of the OVX rats with estrogen augmented the oxytocin-induced running activity twofold, and increased the Oxtr mRNA in the VMH threefold. During the estrus cycle locomotor activity spontaneously increased in the dark period of proestrus. The Oxtr mRNA was up-regulated in the proestrus afternoon. Blockade of oxytocin neurotransmission by its antagonist before the onset of the dark period of proestrus decreased the following nocturnal locomotor activity. These findings demonstrate that Oxtr in the VMH is involved in the induction of running behavior and that estrogen facilitates this effect by means of Oxtr up-regulation, suggesting the involvement of oxytocin in the locomotor activity of proestrus female rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. The effects of distal limb segment shortening on locomotor efficiency in sloped terrain: implications for Neandertal locomotor behavior.

    PubMed

    Higgins, Ryan W; Ruff, Christopher B

    2011-11-01

    Past studies of human locomotor efficiency focused on movement over flat surfaces and concluded that Neandertals were less efficient than modern humans due to a truncated limb morphology, which may have developed to aid thermoregulation in cold climates. However, it is not clear whether this potential locomotor disadvantage would also exist in nonflat terrain. This issue takes on added importance since Neandertals likely spent a significant proportion of their locomotor schedule on sloped, mountainous terrains in the Eurasian landscape. Here a model is developed that determines the relationship between lower limb segment lengths, terrain slope, excursion angle at the hip, and step length. The model is applied to Neandertal and modern human lower limb reconstructions. In addition, for a further independent test that also allows more climateterrain cross comparisons, the same model is applied to bovids living in different terrains and climates. Results indicate that: (1) Neandertals, despite exhibiting shorter lower limbs, would have been able to use similar stride frequencies per speed as longer-limbed modern humans on sloped terrain, due to their lower crural indices; and (2) shortened distal limb segments are characteristic of bovids that inhabit more rugged terrains, regardless of climate. These results suggest that the shortened distal lower limb segments of Neandertals were not a locomotor disadvantage within more rugged environments.

  8. Low-dose effect of ethanol on locomotor activity induced by activation of the mesolimbic system.

    PubMed

    Milton, G V; Randall, P K; Erickson, C K

    1995-06-01

    Four experiments were designed to study the ability of 0.5 g/kg ethanol (EtOH) intraperitoneally to modify locomotor activity induced by drugs that interact with different sites in the mesolimbic system (MLS) of male Sprague-Dawley rats. Locomotor activity was measured in a doughnut-shaped circular arena after various treatments. EtOH alone did not alter locomotor activity in any of the experiments. Amphetamine (AMP, intraperitoneally or intraaccumbens) increased locomotor activity in a dose-dependent manner, and the presence of EtOH attenuated AMP-induced locomotor activity. Bilateral infusion of GABAA antagonist picrotoxin (PIC) into the ventral tegmental area also increased locomotor activity in a dose-dependent manner, and the presence of EtOH attenuated PIC-induced locomotor activity. On the other hand, the interaction between bilateral infusion of mu-receptor agonist Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAGO) and EtOH on locomotor activity is complex. The highest dose of DAGO that significantly increased locomotor activity was not affected by the presence of EtOH. But, with lower doses of DAGO that either had no effect or a small increase in locomotor activity, the combination of EtOH and DAGO increased and attenuated locomotor activity, respectively. Results from this study support our hypothesis that a low dose of EtOH that does not modify behavior can interact with neurotransmitter systems in the brain and modify drug-induced locomotor activity. Modification of this drug-induced locomotor activity by a low dose of EtOH is dependent on the rate of ongoing locomotor behavior induced by drug and the neurotransmitter substrate that the drug modified to induce locomotor behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. 40 CFR 405.80 - Applicability; description of the ice cream, frozen desserts, novelties and other dairy desserts...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PRODUCTS PROCESSING POINT SOURCE CATEGORY Ice Cream, Frozen Desserts, Novelties and Other Dairy Desserts Subcategory § 405.80 Applicability; description of the ice cream, frozen desserts, novelties and other dairy... manufacture of ice cream, ice milk, sherbert, water ices, stick confections, frozen novelties products,...

  10. Comparison of the MK-801-induced increase in non-rewarded appetitive responding with dopamine agonists and locomotor activity in rats.

    PubMed

    Davis-MacNevin, Parnell L; Dekraker, Jordan; LaDouceur, Liane; Holahan, Matthew R

    2013-09-01

    Systemic administration of the noncompetitive N-methyl-D-aspartate (NMDA)- receptor antagonist, MK-801, has been proposed to model cognitive deficits similar to those seen in patients with schizophrenia. Evidence has shown that MK-801 increases the probability of operant responding during extinction, possibly modeling perseveration, as would be seen in patients with schizophrenia. This MK-801-induced behavioral perseveration is reversed by dopamine receptor antagonism. To further explore the role of dopamine in this behavioral change, the current study sought to determine if the MK-801-induced increase in non-rewarded operant responding could be mimicked by dopamine agonism and determine how it was related to locomotor activity. Male Long Evans rats were treated systemically with MK-801, cocaine, GBR12909 or apomorphine (APO) and given a single trial operant extinction session, followed by a separate assessment of locomotor activity. Both MK-801 (0.05 mg/kg) and cocaine (10 mg/kg) significantly increased responding during the extinction session and both increased horizontal locomotor activity. No dose of GBR-12909 (5, 10 or 20 mg/kg) was found to effect non-rewarded operant responding or locomotor activity. APO (0.05, 0.5, 2 or 5 mg/kg) treatment produced a dose-dependent decrease in both operant responding and locomotor activity. These results suggest the possibility that, rather than a primary influence of increased dopamine concentration on elevating bar-pressing responses during extinction, other neurotransmitter systems may be involved.

  11. An innovative spinal cord injury model for the study of locomotor networks.

    PubMed

    Nistri, A

    2012-03-01

    An acute lesion to the spinal cord triggers complex mechanisms responsible for amplification of the initial damage and its chronicity. In vitro preparations of the rodent spinal cord retain the intrinsic ability to produce locomotor-like discharges from lumbar ventral roots and, thus, offer the opportunity to study the still unclear process of lesion progression in relation to cell number and topography. In addition, these models enable a detailed approach to the molecular mechanisms of damage and to pharmacological tools to counteract them. Using the rat spinal cord in vitro, our laboratory has shown how to reliably produce discrete lesions by applying the glutamate agonist kainate that evokes delayed neuronal loss via a non-apoptotic cell death mechanism termed parthanatos. Parthanatos is believed to be due to mitochondrial damage and exhaustion of cell energy stores caused by hyperactivation of enzymatic systems initially set to repair DNA damage. Locomotor network activity is irreversibly destroyed by kainate in a virtually all-or-none manner, suggesting destruction of a highly-vulnerable cell population crucial for the expression of locomotion. Hypoxic challenge to the spinal cord together with toxic radicals primarily damages white matter cells with deficit (without full suppression) of locomotor network function, while neurons are less vulnerable. Pharmacological agents to inhibit different targets involved in the early pathophysiology of spinal injury provided limited success, indicating that novel approaches based on newly identified steps in the biochemical cascade leading to cell death should be investigated for their potential to improve the outcome of spinal cord injury.

  12. An In Vitro Spinal Cord–Hindlimb Preparation for Studying Behaviorally Relevant Rat Locomotor Function

    PubMed Central

    Hayes, Heather Brant; Chang, Young-Hui; Hochman, Shawn

    2009-01-01

    Although the spinal cord contains the pattern-generating circuitry for producing locomotion, sensory feedback reinforces and refines the spatiotemporal features of motor output to match environmental demands. In vitro preparations, such as the isolated rodent spinal cord, offer many advantages for investigating locomotor circuitry, but they lack the natural afferent feedback provided by ongoing locomotor movements. We developed a novel preparation consisting of an isolated in vitro neonatal rat spinal cord oriented dorsal-up with intact hindlimbs free to step on a custom-built treadmill. This preparation combines the neural accessibility of in vitro preparations with the modulatory influence of sensory feedback from physiological hindlimb movement. Locomotion induced by N-methyl d-aspartate and serotonin showed kinematics similar to that of normal adult rat locomotion. Changing orientation and ground interaction (dorsal-up locomotion vs ventral-up air-stepping) resulted in significant kinematic and electromyographic changes that were comparable to those reported under similar mechanical conditions in vivo. We then used two mechanosensory perturbations to demonstrate the influence of sensory feedback on in vitro motor output patterns. First, swing assistive forces induced more regular, robust muscle activation patterns. Second, altering treadmill speed induced corresponding changes in stride frequency, confirming that changes in sensory feedback can alter stride timing in vitro. In summary, intact hindlimbs in vitro can generate behaviorally appropriate locomotor kinematics and responses to sensory perturbations. Future studies combining the neural and chemical accessibility of the in vitro spinal cord with the influence of behaviorally appropriate hindlimb movements will provide further insight into the operation of spinal motor pattern-generating circuits. PMID:19073815

  13. Comparison of toluene-induced locomotor activity in Four Mouse Strains

    PubMed Central

    Bowen, Scott E; Kimar, Sarah; Irtenkauf, Susan

    2010-01-01

    The mechanisms by which abused inhalants exert their neurobehavioral effects are only partially understood. In research with other drugs of abuse, specific inbred mouse strains have been useful in exploring genetic loci important to variation in behavioral reactions to these drugs. In the present investigation, mice from three inbred strains (Balb/cByj, C57BL/6J and DBA/2J) and one outbred strain (Swiss Webster) were studied for their acute and chronic sensitivity to toluene-induced changes in locomotor activity. Mice were exposed to toluene (0, 100, 2000, 8000, 10000 ppm) for 30 min in static exposure chambers equipped with activity monitors. In the acute condition, concentrations of toluene <8000 ppm increased ambulatory distance while the concentrations of ≥8000 ppm induced temporally biphasic effects with initial increases in activity followed by hypoactivity. Between-group differences in absolute locomotor activity levels were evident. The inbred Balb/cByj and DBA/2J strains as well as the outbred Swiss Webster strain o