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Sample records for striatal win binding

  1. Striatal dopamine transporter binding correlates with serum BDNF levels in patients with striatal dopaminergic neurodegeneration

    DEFF Research Database (Denmark)

    Ziebell, Morten; Khalid, Usman; Klein, Anders B

    2012-01-01

    BDNF levels in patients with parkinsonism. Twenty-one patients with abnormal in vivo striatal dopamine transporter (DAT) binding as evidenced with [(123)I]PE2I SPECT brain scanning were included. Samples for serum BDNF levels were collected at the time of the SPECT scanning, and BDNF was measured...

  2. Reduced striatal D2 receptor binding in myoclonus-dystonia

    International Nuclear Information System (INIS)

    Beukers, R.J.; Weisscher, N.; Tijssen, M.A.J.; Booij, J.; Zijlstra, F.; Amelsvoort, T.A.M.J. van

    2009-01-01

    To study striatal dopamine D 2 receptor availability in DYT11 mutation carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D). Fifteen DYT11 mutation carriers (11 clinically affected) and 15 age- and sex-matched controls were studied using 123 I-IBZM SPECT. Specific striatal binding ratios were calculated using standard templates for striatum and occipital areas. Multivariate analysis with corrections for ageing and smoking showed significantly lower specific striatal to occipital IBZM uptake ratios (SORs) both in the left and right striatum in clinically affected patients and also in all DYT11 mutation carriers compared to control subjects. Our findings are consistent with the theory of reduced dopamine D 2 receptor (D2R) availability in dystonia, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out. (orig.)

  3. Dysregulation of Striatal Dopamine Receptor Binding in Suicide.

    Science.gov (United States)

    Fitzgerald, Megan L; Kassir, Suham A; Underwood, Mark D; Bakalian, Mihran J; Mann, J John; Arango, Victoria

    2017-03-01

    Inconsistent evidence implicates disruptions of striatal dopaminergic indices in suicide and major depression. To determine whether there are alterations in the striatal dopamine system in suicide, we conducted a quantitative autoradiographic survey of dopamine transporter (DAT; [ 3 H]mazindol), D1 receptor ([ 3 H]SCH23390), and D2 receptor ([ 3 H]sulpiride) binding in the dorsal striatum postmortem from matched suicides and controls. Axis I and axis II psychiatric diagnosis, recent treatment history, and early life adversity (ELA) were determined by psychological autopsy. Mean DAT, D2, and D1 receptor binding did not differ in suicide. However, there was a positive correlation between D1 and D2 receptor binding in the dorsal striatum of control subjects (R 2 =0.31, p<0.05) that was not present in suicides (R 2 =0.00, p=0.97). In suicides and controls with reported ELA, there was no correlation between striatal DAT and D1 receptor binding (R 2 =0.07, p=0.33), although DAT and D1 receptor binding was positively correlated in subjects with no report of ELA (R 2 =0.32, p<0.05). After controlling for age, there were no significant ELA-related mean differences. Binding of D1 receptors and DAT throughout the striatum correlated negatively with age (D1 receptor: R 2 =0.12, p<0.05; DAT: R 2 =0.36, p<0.001). There appears to be an imbalance in dopaminergic receptor and transporter expression related to suicide that differs from that associated with ELA or age.

  4. Striatal connectivity changes following gambling wins and near-misses: Associations with gambling severity

    NARCIS (Netherlands)

    Holst, R.J. van; Chase, H.W.; Clark, L.

    2014-01-01

    Frontostriatal circuitry is implicated in the cognitive distortions associated with gambling behaviour. 'Near-miss' events, where unsuccessful outcomes are proximal to a jackpot win, recruit overlapping neural circuitry with actual monetary wins. Personal control over a gamble (e.g., via choice) is

  5. Striatal connectivity changes following gambling wins and near-misses: Associations with gambling severity

    Directory of Open Access Journals (Sweden)

    Ruth J. van Holst

    2014-01-01

    These findings corroborate the ‘non-categorical’ nature of reward processing in gambling: near-misses and full-misses are objectively identical outcomes that are processed differentially. Ventral striatal connectivity with the insula correlated positively with gambling severity in the illusion of control contrast, which could be a risk factor for the cognitive distortions and loss-chasing that are characteristic of problem gambling.

  6. Synthesis and binding to striatal membranes of non carrier added I-123 labeled 4'-iodococaine

    International Nuclear Information System (INIS)

    Metwally, S.A.M.; Gatley, S.J.; Wolf, A.P.; Yu, D.-W.

    1992-01-01

    An 123 I labeled cocaine analog, 4'-[ 123 I]iodococaine, has been prepared by oxidative destannylation of the tributyltin analog and shown to interact with cocaine binding sites in rat brain striatal membranes. It may thus be a suitable SPECT radiotracer for studies of the dopamine reuptake site in neurodegenerative diseases. (Author)

  7. Writer's cramp: restoration of striatal D2-binding after successful biofeedback-based sensorimotor training.

    NARCIS (Netherlands)

    Berger, H.J.C.; Werf, S.P. van der; Horstink, C.A.; Cools, A.R.; Oyen, W.J.G.; Horstink, M.W.I.M.

    2007-01-01

    INTRODUCTION: Previous studies of writer's cramp have detected cerebral sensorimotor abnormalities in this disorder and, more specifically, a reduced striatal D2-binding as assessed by [(123)I]IBZM SPECT. However, empirical data were lacking about the influence of effective biofeedback-based

  8. Differential sensitivity to NaCl for inhibitors and substrates that recognize mutually exclusive binding sites on the neuronal transporter of dopamine in rat striatal membranes.

    Science.gov (United States)

    Tidjane Corera, A; Do-Régo, J C; Costentin, J; Bonnet, J J

    2001-03-01

    Addition of NaCl (90--290 mM) to a 10 mM Na(+) medium did not significantly modify B(max) and K(d) values for [3H]mazindol binding to the dopamine neuronal transporter (DAT) studied on rat striatal membranes at 20 degrees C. Addition of NaCl differentially affected the ability of other uptake inhibitors and substrates to block the [3H]mazindol binding. Ratios of 50% inhibiting concentrations calculated for 290 and 90 mM NaCl allowed to distinguish three groups of agents: substrates which were more potent in the presence of 290 mM NaCl (group 1; ratio mazindol, benztropine, nomifensine). However, agents from these three groups recognize mutually exclusive binding sites since in interaction studies the presence of WIN 35,428 (group 2) or mazindol (group 3) increased the 50% inhibiting concentrations of D-amphetamine (group 1) and WIN 35,428 on the [3H]mazindol binding to theoretical values expected for a competition of all of these compounds for the same binding domain on the DAT.

  9. Prenatal stress induces increased striatal dopamine transporter binding in adult nonhuman primates.

    Science.gov (United States)

    Converse, Alexander K; Moore, Colleen F; Moirano, Jeffrey M; Ahlers, Elizabeth O; Larson, Julie A; Engle, Jonathan W; Barnhart, Todd E; Murali, Dhanabalan; Christian, Bradley T; DeJesus, Onofre T; Holden, James E; Nickles, Robert J; Schneider, Mary L

    2013-10-01

    To determine the effects in adult offspring of maternal exposure to stress and alcohol during pregnancy, we imaged striatal and midbrain dopamine transporter (DAT) binding by positron emission tomography in rhesus monkeys (Macaca mulatta). We also evaluated the relationship between DAT binding and behavioral responses previously found to relate to dopamine D2 receptor density (responsivity to tactile stimuli, performance on a learning task, and behavior during a learning task). Subjects were adult offspring derived from a 2 × 2 experiment in which pregnant monkeys were randomly assigned to control, daily mild stress exposure (acoustic startle), voluntary consumption of moderate-level alcohol, or both daily stress and alcohol. Adult offspring (n = 38) were imaged by positron emission tomography with the DAT ligand [(18)F]2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane ([(18)F]FECNT). Results showed that prenatal stress yielded an overall increase of 15% in [(18)F]FECNT binding in the striatum (p = .016), 17% greater binding in the putamen (p = .012), and 13% greater binding in the head of the caudate (p = .028) relative to animals not exposed to prenatal stress. Striatal [(18)F]FECNT binding correlated negatively with habituation to repeated tactile stimulation and positively with tactile responsivity. There were no significant effects of prenatal alcohol exposure on [(18)F]FECNT binding. Maternal exposure to mild daily stress during pregnancy yielded increases in striatal DAT availability that were apparent in adult offspring and were associated with behavioral characteristics reflecting tactile hyperresponsivity, a condition associated with problem behaviors in children. © 2013 Society of Biological Psychiatry.

  10. Timing of caloric intake during weight loss differentially affects striatal dopamine transporter and thalamic serotonin transporter binding.

    Science.gov (United States)

    Versteeg, Ruth I; Schrantee, Anouk; Adriaanse, Sofie M; Unmehopa, Unga A; Booij, Jan; Reneman, Liesbeth; Fliers, Eric; la Fleur, Susanne E; Serlie, Mireille J

    2017-10-01

    Recent studies have shown that meal timing throughout the day contributes to maintaining or regaining weight after hypocaloric diets. Although brain serotonin and dopamine are well known to be involved in regulating feeding, it is unknown whether meal timing during energy restriction affects these neurotransmitter systems. We studied the effect of a 4 wk hypocaloric diet with either 50% of daily calories consumed at breakfast (BF group) or at dinner (D group) on hypothalamic and thalamic serotonin transporter (SERT) binding and on striatal dopamine transporter (DAT) binding. The BF and D groups lost a similar amount of weight. Striatal DAT and thalamic SERT binding increased in the BF group, while decreasing in the D group after the diet (ΔDAT 0.37 ± 0.63 vs. -0.53 ± 0.77, respectively; P = 0.005; ΔSERT 0.12 ± 0.25 vs. -0.13 ± 0.26 respectively, P = 0.032). Additional voxel-based analysis showed an increase in DAT binding in the ventral striatum in the BF group and a decrease in the dorsal striatum in the D group. During weight loss, striatal DAT and thalamic SERT binding increased weight independently when 50% of daily calories were consumed at breakfast, whereas it decreased when caloric intake was highest at dinner. These findings may contribute to the earlier reported favorable effect of meal timing on weight maintenance after hypocaloric diets.-Versteeg, R. I., Schrantee, A., Adriaanse, S. M., Unmehopa, U. A., Booij, J., Reneman, L., Fliers, E., la Fleur, S. E., Serlie, M. J. Timing of caloric intake during weight loss differentially affects striatal dopamine transporter and thalamic serotonin transporter binding. © FASEB.

  11. No association between striatal dopamine transporter binding and body mass index

    DEFF Research Database (Denmark)

    van de Giessen, Elsmarieke; Hesse, Swen; Caan, Matthan W A

    2013-01-01

    Dopamine is one among several neurotransmitters that regulate food intake and overeating. Thus, it has been linked to the pathophysiology of obesity and high body mass index (BMI). Striatal dopamine D(2) receptor availability is lower in obesity and there are indications that striatal dopamine tr...

  12. Leptin Increases Striatal Dopamine D2 Receptor Binding in Leptin-Deficient Obese (ob/ob) Mice

    Energy Technology Data Exchange (ETDEWEB)

    Pfaffly, J.; Michaelides, M.; Wang, G-J.; Pessin, J.E.; Volkow, N.D.; Thanos, P.K.

    2010-06-01

    Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R-binding differences contribute to the phenotypic behaviors of leptin-deficient ob/ob mice, and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Basal striatal D2R binding (measured with autoradiography [{sup 3}H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice, leptin decreased striatal D2R binding, whereas, in ob/ob mice, leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2R expression in striatum and that these effects are genotype/phenotype dependent.

  13. Striatal Dopamine Transporter Binding Does Not Correlate with Clinical Severity in Dementia with Lewy Bodies

    DEFF Research Database (Denmark)

    Ziebell, Morten; Andersen, Birgitte B; Pinborg, Lars H

    2013-01-01

    cognitively evaluated with the Mini Mental State Examination. RESULTS: There was no correlation between Mini Mental State Examination, Hoehn and Yahr score, fluctuations or hallucinations, and striatal DAT availability as measured with (123)I-PE2I and SPECT. CONCLUSION: In patients with newly diagnosed DLB...

  14. Relationship between striatal [123I]β-CIT binding and four major clinical signs in Parkinson's disease

    International Nuclear Information System (INIS)

    Shinotoh, Hitoshi; Uchida, Yoshitaka; Ito, Hisao; Hattori, Takamichi

    2000-01-01

    We investigated the correlation between clinical severity and striatal [ 123 I]β-CIT binding in 12 patients with Parkinson's Disease (PD: 6 men and 6 women, age: 65±7 years, Hoehn-Yahr stage: 1 to 3). The clinical severity of PD patients was measured with the Unified Parkinson's Disease Rating Scale (UPDRS) after withdrawal of antiparkinsonian medication at least 12 hours before assessment. [ 123 I]β-CIT binding in the caudate and putamen was measured at 3 hours [V'' 3 (day 1)], and at 24 hours [V'' 3 (day 2)] after tracer injection with small square ROIs. The specific striatal uptake index (day 2) was calculated with large square ROIs that encompassed the whole striatum. The best correlation (r=-0.82, p 3 (day 2) and the motor UPDRS scores. When the motor UPDRS scores were divided into four subscales, bradykinesia was the only sign that correlated significantly with putamenal V'' 3 (day 2) (r=-0.81, p 123 I]β-CIT SPECT is a useful marker of disease severity in PD with potential utility in the serial monitoring of disease progression. (author)

  15. Repeated administration of D-amphetamine induces loss of [{sup 123}I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    Energy Technology Data Exchange (ETDEWEB)

    Booij, Jan [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands)]. E-mail: j.booij@amc.uva.nl; Bruin, Kora de [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands); Gunning, W. Boudewijn [Department of Neurology, Epilepsy Centre Kempenhaeghe, 5590 AB Heeze (Netherlands)

    2006-04-15

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([{sup 123}I]FP-CIT). Methods: Groups of male rats (n=10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [{sup 123}I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. Results: In D-AMPH but not METH-treated rats, striatal [{sup 123}I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. Conclusion: These data show that [{sup 123}I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo.

  16. Relationships between the catechol substrate binding site and amphetamine, cocaine, and mazindol binding sites in a kinetic model of the striatal transporter of dopamine in vitro.

    Science.gov (United States)

    Wayment, H; Meiergerd, S M; Schenk, J O

    1998-05-01

    Experiments were conducted to determine how (-)-cocaine and S(+)-amphetamine binding sites relate to each other and to the catechol substrate site on the striatal dopamine transporter (sDAT). In controls, m-tyramine and S(+)-amphetamine caused release of dopamine from intracellular stores at concentrations > or = 12-fold those observed to inhibit inwardly directed sDAT activity for dopamine. In preparations from animals pretreated with reserpine, m-tyramine and S(+)-amphetamine caused release of preloaded dopamine at concentrations similar to those that inhibit inwardly directed sDAT activity. S(+)-Amphetamine and m-tyramine inhibited sDAT activity for dopamine by competing for a common binding site with dopamine and each other, suggesting that phenethylamines are substrate analogues at the plasmalemmal sDAT. (-)-Cocaine inhibited sDAT at a site separate from that for substrate analogues. This site is mutually interactive with the substrate site (K(int) = 583 nM). Mazindol competitively inhibited sDAT at the substrate analogue binding site. The results with (-)-cocaine suggest that the (-)-cocaine binding site on sDAT is distinct from that of hydroxyphenethylamine substrates, reinforcing the notion that an antagonist for (-)-cocaine binding may be developed to block (-)-cocaine binding with minimal effects on dopamine transporter activity. However, a strategy of how to antagonize drugs of abuse acting as substrate analogues is still elusive.

  17. Mitigation win-win

    Science.gov (United States)

    Moran, Dominic; Lucas, Amanda; Barnes, Andrew

    2013-07-01

    Win-win messages regarding climate change mitigation policies in agriculture tend to oversimplify farmer motivation. Contributions from psychology, cultural evolution and behavioural economics should help to design more effective policy.

  18. In vivo labeling of cocaine receptors with 3H-(-) cocaine, 3H-WIN 35,065-2 and 3H-WIN 35,428

    International Nuclear Information System (INIS)

    Scheffel, U.; Boja, J.W.; Stathis, M.; Kuhar, M.J.

    1990-01-01

    11 C-(-)cocaine (-COC) has recently been employed to image -COC binding sites in vivo using PET. Two analogs of -COC, WIN 35,065-2 (WIN-2) and WIN 35,428 (CFT), have been shown in vitro to exhibit higher affinity for the -COC receptor than -COC. The present study evaluates 3 H-WIN-2 and 3 H-CFT as in vivo receptor labels in mice with a view towards the use of these compounds as PET ligands for -COC receptors in the living human brain. 3 H-labeled -COC, WIN-2 and CFT were injected i.v. into mice and their specific binding in the CNS determined. Peak striatal/cerebellar (S/C) ratios were reached at 5 minutes post injection with -COC (1.56), at 45 minutes with 3 H-WIN-2 (3.30) and 60 minutes with 3 H-CFT (4.0). The specificity of in vivo binding of 3 H-WIN-2 and 3 H-CFT was tested by pre-injection of various drugs. Binding of 3 H-WIN-2 and 3 H-CFT was dose-dependently blocked by cold WIN-2 and CFT, and by dopamine uptake site inhibitors (mazindol, GBR 12,909, nomifensine), but not by (+)COC, paroxetine and desipramine. The data indicate that 3 H-WIN-2 and 3 H-CFT exhibit improved in vivo binding (higher S/C ratios, longer retention time at the -COC receptor/dopamine transporter) compared to -COC and support their testing in PET studies

  19. WIN 35,428 and mazindol are mutually exclusive in binding to the cloned human dopamine transporter.

    Science.gov (United States)

    Xu, C; Reith, M E

    1997-08-01

    It has been suggested that cocaine and mazindol bind to separate sites on the dopamine transporter. In the present study, we address this issue by examining the inhibition by mazindol of the binding of [3H]WIN 35,428 ([3H]2beta-carbomethyoxy-3beta-(4-fluorophenyl)-tropane), a phenyltropane analog of cocaine, and the inhibition by WIN 35,428 of [3H]mazindol binding to the cloned human dopamine transporter expressed in C6 glioma cells. The design involved the construction of inhibition curves at six widely different radioligand levels, enabling the distinction between the nonlinear hyperbolic competition (i.e., negative allosteric) model and the competitive (i.e., mutually exclusive binding) model. Nonlinear computer curve-fitting analysis indicated no difference in the goodness of fit between the two models; the negative allosteric model indicated an extremely high allosteric constant of approximately > or = 100, which practically equates to the competitive model. The present results suggest that complex interactions reported between cocaine and mazindol in inhibiting dopamine transport are beyond the level of ligand recognition.

  20. Decreased striatal dopamine transporter binding assessed with [123I] FP-CIT in first-episode schizophrenic patients with and without short-term antipsychotic-induced parkinsonism.

    Science.gov (United States)

    Mateos, Jose J; Lomeña, Francisco; Parellada, Eduardo; Font, Mireia; Fernandez, Emili; Pavia, Javier; Prats, Alberto; Pons, Francisca; Bernardo, Miquel

    2005-09-01

    Drug-induced parkinsonism (DIP) is one of the main causes of treatment drop-out in schizophrenic patients causing a high incidence of relapse that leads patients to a bad clinical prognosis. The dopaminergic nigrostriatal pathway is involved in the movement control, so the study of the dopamine transporter (DAT) could be of great value to determine its implication in the appearance of DIP. The goal of the study is to determine the striatal DAT binding assessed with [(123)I] FP-CIT SPECT in first-episode neuroleptic-naive schizophrenic in-patients with DIP after short-term antipsychotic treatment. The [(123)I] FP-CIT binding ratios of ten schizophrenic in-patients who developed DIP during the first 4-week period of risperidone treatment (6+/-2 mg/day) were compared with ten schizophrenic in-patients treated with the same doses of risperidone and who do not developed DIP and with ten age-matched healthy subjects. Quantitative analyses of SPECTs were performed using regions of interest located in caudate, putamen and occipital cortex. Parkinsonism was assessed by the Simpson-Angus Scale and the psychopathological status by the Clinical General Impression and Positive and Negative Syndrome Scales. Whole striatal [(123)I] FP-CIT binding ratios were significantly lower in patients with and without DIP than in healthy subjects (p<0.001). This was also observed in whole putamen (p<0.001) and caudate nucleus (p<0.001). Females showed higher whole striatal [(123)I] FP-CIT binding ratios than males (p<0.05). No differences in psychopathological scales were observed between patients with and without DIP. Our first-episode schizophrenic patients with and without DIP after short-term risperidone treatment have a decreased striatal DAT binding assessed with [(123)I] FP-CIT. This alteration could be related to the schizophrenic disease or may be secondary to the antipsychotic treatment.

  1. Pharmacological modifications of dopamine transmission do not influence the striatal in vivo binding of [3H]mazindol or [3H]cocaine in mice.

    Science.gov (United States)

    Thibaut, F; Bonnet, J J; Vaugeois, J M; Costentin, J

    1996-03-01

    We have considered the in vivo striatal binding of two ligands of the neuronal dopamine uptake complex: [3H]cocaine and [3H]mazindol. The [3H]cocaine tracer dose labelled the dopamine uptake complex in striatum but not the noradrenaline complex in cerebellum. On the contrary, the [3H]mazindol tracer dose induced a marked labelling of the noradrenaline uptake complex in cerebellum; its prevention by desipramine (5 mg/kg) increased simultaneously the cerebral bioavailability and thereby the striatal labelling of the dopamine transporter. In mice submitted to treatments modifying dopaminergic transmission either to decrease it (gammabutyrolactone, 750 mg/kg, i.p.) or to increase it (L-DOPA, 200 mg/kg, i.p., dexamphetamine, 4 mg/kg, s.c., or their combination), only dexamphetamine pretreatment significantly reduced [3H]cocaine and [3H]mazindol binding. Thus it appears that the level of dopamine transmission would not interfere with the in vivo quantification of striatal dopamine uptake sites assessed with either ligands.

  2. In vivo labeling of cocaine receptors with sup 3 H-(-) cocaine, sup 3 H-WIN 35,065-2 and sup 3 H-WIN 35,428

    Energy Technology Data Exchange (ETDEWEB)

    Scheffel, U.; Boja, J.W.; Stathis, M.; Kuhar, M.J. (Johns Hopkins Medical Institutions, Baltimore, MD (United States))

    1990-02-26

    {sup 11}C-(-)cocaine (-COC) has recently been employed to image -COC binding sites in vivo using PET. Two analogs of -COC, WIN 35,065-2 (WIN-2) and WIN 35,428 (CFT), have been shown in vitro to exhibit higher affinity for the -COC receptor than -COC. The present study evaluates {sup 3}H-WIN-2 and {sup 3}H-CFT as in vivo receptor labels in mice with a view towards the use of these compounds as PET ligands for -COC receptors in the living human brain. {sup 3}H-labeled -COC, WIN-2 and CFT were injected i.v. into mice and their specific binding in the CNS determined. Peak striatal/cerebellar (S/C) ratios were reached at 5 minutes post injection with -COC (1.56), at 45 minutes with {sup 3}H-WIN-2 (3.30) and 60 minutes with {sup 3}H-CFT (4.0). The specificity of in vivo binding of {sup 3}H-WIN-2 and {sup 3}H-CFT was tested by pre-injection of various drugs. Binding of {sup 3}H-WIN-2 and {sup 3}H-CFT was dose-dependently blocked by cold WIN-2 and CFT, and by dopamine uptake site inhibitors (mazindol, GBR 12,909, nomifensine), but not by (+)COC, paroxetine and desipramine. The data indicate that {sup 3}H-WIN-2 and {sup 3}H-CFT exhibit improved in vivo binding (higher S/C ratios, longer retention time at the -COC receptor/dopamine transporter) compared to -COC and support their testing in PET studies.

  3. No significant effects of single intravenous, single oral and subchronic oral administration of acetylcholinesterase inhibitors on striatal [{sup 123}I]FP-CIT binding in rats

    Energy Technology Data Exchange (ETDEWEB)

    Knol, R.J.J.; Booij, J. [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Graduate School of Neurosciences, Amsterdam (Netherlands); Bruin, K. de; Eck-Smit, B.L.F. van [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands)

    2008-03-15

    [{sup 123}I]FP-CIT SPECT is a valuable diagnostic tool to discriminate Lewy body dementia from Alzheimer's dementia. To date, however, it is uncertain whether the frequently used acetylcholinesterase inhibitors (AChEIs) by demented patients, have an effect on [{sup 123}I]FP-CIT binding to dopamine transporters (DATs). Earlier animal studies showed a decline of DAT availability after acute intravenous injection of AChEIs. The aim of this study was to investigate effects of single intravenous, single oral and subchronic oral administration of AChEIs on DAT availability in the rat brain as measured by [{sup 123}I]FP-CIT. Biodistribution studies were performed in Wistar rats (n = 5-16 per group). Before [{sup 123}I]FP-CIT injection, rats were injected intravenously with a single dose of the AChEI rivastigmine (2.5 mg/kg body weight) or donepezil (0.5 mg/kg), the DAT-blocker methylphenidate (10 mg/kg) or saline. A second group was orally treated with a single dose of rivastigmine or donepezil (2.5 mg/kg), methylphenidate (10 mg/kg) or saline before injection of [{sup 123}I]FP-CIT. Studies were also performed in rats that were orally treated during 14 consecutive days with either rivastigmine (1 mg/kg daily), donepezil (1.5 mg/kg daily), methylphenidate (2.5 mg/kg) or saline. Brain parts were assayed in a gamma counter, and specific striatum/cerebellum ratios were calculated for the [{sup 123}I]FP-CIT binding to DATs. No significant effects of either single intravenous, single oral or subchronic oral administration of AChEIs on striatal FP-CIT binding could be detected. Single pretreatment with methylphenidate resulted in an expected significantly lower striatal FP-CIT binding. We conclude that in rats, single intravenous and single or subchronic oral administration of the tested AChEIs does not lead to an important alteration of [{sup 123}I]FP-CIT binding to striatal DATs. Therefore, it is unlikely that these drugs will induce large effects on the interpretation of

  4. Cations affect [3H]mazindol and [3H]WIN 35,428 binding to the human dopamine transporter in a similar fashion.

    Science.gov (United States)

    Wu, Q; Coffey, L L; Reith, M E

    1997-09-01

    The present study addresses the possibility that there are different cocaine-related and mazindol-related binding domains on the dopamine transporter (DAT) that show differential sensitivity to cations. The effects of Zn2+, Mg2+, Hg2+, Li+, K+, and Na+ were assessed on the binding of [3H]mazindol and [3H]WIN 35,428 to the human (h) DAT expressed in C6 glioma cells under identical conditions for intact cell and membrane assays. The latter were performed at both 0 and 21 degrees C. Zn2+ (30-100 microM) stimulated binding of both radioligands to membranes, with a relatively smaller effect for [3H]mazindol; Mg2+ (0.1-100 microM) had no effect; Hg2+ at approximately 3 microM stimulated binding to membranes, with a relatively smaller effect for [3H]mazindol than [3H]WIN 35,428 at 0 degrees C, and at 30-100 microM inhibited both intact cell and membrane binding; Li+ and K+ substitution (30-100 mM) inhibited binding to membranes more severely than to intact cells; and Na+ substitution was strongly stimulatory. With only a few exceptions, the patterns of ion effects were remarkably similar for both radioligands at both 0 and 21 degrees C, suggesting the involvement of common binding domains on the hDAT impacted similarly by cations. Therefore, if there are different binding domains for WIN 35,428 and mazindol, these are not affected differentially by the cations studied in the present experiments, except for the stimulatory effect of Zn2+ at 0 and 21 degrees C and Hg2+ at 0 degrees C.

  5. Varenicline increases in vivo striatal dopamine D2/3 receptor binding: an ultra-high-resolution pinhole [123I]IBZM SPECT study in rats

    International Nuclear Information System (INIS)

    Crunelle, Cleo L.; Wit, Tim C. de; Bruin, Kora de; Ramakers, Ruud M.; Have, Frans van der; Beekman, Freek J.; Brink, Wim van den; Booij, Jan

    2012-01-01

    Introduction: Ex vivo storage phosphor imaging rat studies reported increased brain dopamine D 2/3 receptor (DRD 2/3 ) availability following treatment with varenicline, a nicotinergic drug. However, ex vivo studies can only be performed using cross-sectional designs. Small-animal imaging offers the opportunity to perform serial assessments. We evaluated whether high-resolution pinhole single photon emission computed tomography (SPECT) imaging in rats was able to reproduce previous ex vivo findings. Methods: Rats were imaged for baseline striatal DRD 2/3 availability using ultra-high-resolution pinhole SPECT (U-SPECT-II) and [ 123 I]IBZM as a radiotracer, and randomized to varenicline (n=7; 2 mg/kg) or saline (n=7). Following 2 weeks of treatment, a second scan was acquired. Results: Significantly increased striatal DRD 2/3 availability was found following varenicline treatment compared to saline (time⁎treatment effect): posttreatment difference in binding potential between groups corrected for initial baseline differences was 2.039 (P=.022), indicating a large effect size (d=1.48). Conclusions: Ultra-high-resolution pinhole SPECT can be used to assess varenicline-induced changes in DRD 2/3 availability in small laboratory animals over time. Future small-animal studies should include imaging techniques to enable repeated within-subjects measurements and reduce the amount of animals.

  6. A C-terminal PDZ domain-binding sequence is required for striatal distribution of the dopamine transporter

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Hansen, Freja Herborg; Sørensen, Gunnar

    2013-01-01

    transporter expression in the striatum, causing hyperlocomotion and attenuated response to amphetamine. In cultured dopaminergic neurons and striatal slices from dopamine transporter-AAA mice, we find markedly reduced dopamine transporter surface levels and evidence for enhanced constitutive internalization....... In dopamine transporter-AAA neurons, but not in wild-type neurons, surface levels are rescued in part by expression of a dominant-negative dynamin mutation (K44A). Our findings suggest that PDZ-domain interactions are critical for synaptic distribution of dopamine transporter in vivo and thereby for proper...

  7. COMT Val(158) met genotype and striatal D(2/3) receptor binding in adults with 22q11 deletion syndrome.

    LENUS (Irish Health Repository)

    Boot, Erik

    2011-09-01

    Although catechol-O-methyltransferase (COMT) activity evidently affects dopamine function in prefrontal cortex, the contribution is assumed less significant in striatum. We studied whether a functional polymorphism in the COMT gene (Val(158) Met) influences striatal D(2\\/3) R binding ratios (D(2\\/3) R BP(ND) ) in 15 adults with 22q11 deletion syndrome and hemizygous for this gene, using single photon emission computed tomography and the selective D(2\\/3) radioligand [(123) I]IBZM. Met hemizygotes had significantly lower mean D(2\\/3) R BPND than Val hemizygotes. These preliminary data suggest that low COMT activity may affect dopamine levels in striatum in humans and this may have implications for understanding the contribution of COMT activity to psychiatric disorders.

  8. Tyrosine hydroxylase immunoreactivity and [3H]WIN 35,428 binding to the dopamine transporter in a hamster model of idiopathic paroxysmal dystonia

    International Nuclear Information System (INIS)

    Nobrega, J.N.; Gernert, M.; Loescher, W.; Raymond, R.; Belej, T.; Richter, A.

    1999-01-01

    Recent pharmacological studies and receptor analyses have suggested that dopamine neurotransmission is enhanced in mutant dystonic hamsters (dt sz ), a model of idiopathic paroxysmal dystonia which displays attacks of generalized dystonia in response to mild stress. In order to further characterize the nature of dopamine alterations, the present study investigated possible changes in the number of dopaminergic neurons, as defined by tyrosine hydroxylase immunohistochemistry, as well as binding to the dopamine transporter labelled with [ 3 H]WIN 35,428 in dystonic hamsters. No differences in the number of tyrosine hydroxylase-immunoreactive neurons were found within the substantia nigra and ventral tegmental area of mutant hamsters compared to non-dystonic control hamsters. Similarly, under basal conditions, i.e. in the absence of a dystonic episode, no significant changes in [ 3 H]WIN 35,428 binding were detected in dystonic brains. However, in animals killed during the expression of severe dystonia, significant decreases in dopamine transporter binding became evident in the nucleus accumbens and ventral tegmental area in comparison to controls exposed to the same external stimulation. Since stimulation tended to increase [ 3 H]WIN 35,428 binding in control brains, the observed decrease in the ventral tegmental area appeared to be due primarily to the fact that binding was increased less in dystonic brains than in similarly stimulated control animals.This finding could reflect a diminished ability of the dopamine transporter to undergo adaptive changes in response to external stressful stimulation in mutant hamsters. The selective dopamine uptake inhibitor GBR 12909 (20 mg/kg) aggravated dystonia in mutant hamsters, further suggesting that acute alterations in dopamine transporter function during stimulation may be an important component of dystonia in this model. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  9. In vivo effects of olanzapine on striatal dopamine D[sub 2]/D[sub 3] receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Dresel, S.; Rossmueller, B.; Hahn, K.; Tatsch, K. (Department of Nuclear Medicine, University of Munich (Germany)); Mager, T.; Meisenzahl, E.; Moeller, H.J. (Department of Psychiatry, University of Munich (Germany))

    1999-08-01

    suggest an exponential relationship between the daily dose of olanzapine striatal and decreased D[sub 2]/D[sub 3] striatal binding availability. The results are consistent with the findings of in vitro experiments reporting a higher D[sub 2]/D[sub 3] receptor affinity and a similar 5HT[sub 2] receptor affinity of olanzapine as compared with clozapine. Thus, the decreased tendency to induce EPMS at therapeutic doses is not due to the limited occupancy of striatal D[sub 2]/D[sub 3] receptors in vivo. Patients are protected from EPMS by other intrinsic effects of the drug, i.e. the combination of both D[sub 2]/D[sub 3] and 5HT[sub 2] receptor antagonism. (orig.) With 4 figs., 3 tabs., 33 refs.

  10. In vivo effects of olanzapine on striatal dopamine D{sub 2}/D{sub 3} receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Dresel, S.; Rossmueller, B.; Hahn, K.; Tatsch, K. [Department of Nuclear Medicine, University of Munich (Germany); Mager, T.; Meisenzahl, E.; Moeller, H.J. [Department of Psychiatry, University of Munich (Germany)

    1999-08-01

    suggest an exponential relationship between the daily dose of olanzapine striatal and decreased D{sub 2}/D{sub 3} striatal binding availability. The results are consistent with the findings of in vitro experiments reporting a higher D{sub 2}/D{sub 3} receptor affinity and a similar 5HT{sub 2} receptor affinity of olanzapine as compared with clozapine. Thus, the decreased tendency to induce EPMS at therapeutic doses is not due to the limited occupancy of striatal D{sub 2}/D{sub 3} receptors in vivo. Patients are protected from EPMS by other intrinsic effects of the drug, i.e. the combination of both D{sub 2}/D{sub 3} and 5HT{sub 2} receptor antagonism. (orig.) With 4 figs., 3 tabs., 33 refs.

  11. The effects of surgical and chemical lesions on striatal [3H]threo-(+-)-methylphenidate binding: correlation with [3H]dopamine uptake

    International Nuclear Information System (INIS)

    Janowsky, A.; Berger, P.; Long, R.; Paul, S.M.; Schweri, M.M.; Skolnick, P.

    1985-01-01

    The specific binding of [ 3 H]threo-(+-)-methylphenidate to membranes prepared from rat striatum was significantly reduced following either surgical lesions of the medial forebrain bundle or intracerebroventricular administration of 6-hydroxydopamine. The decrease in the density of [ 3 H]threo-(+-)-methylphenidate binding sites in striatum following chemical or surgical denervation was highly correlated with the decrease in [ 3 H]dopamine uptake. In contrast, intracerebroventricular administration of 5,7-dihydroxytryptamine, AF64A, or chronic parenteral administration of reserpine did not alter either the number or apparent affinity of [ 3 H]threo-(+-)-methylphenidate binding sites. These data suggest that the specific binding sites for [ 3 H]threo-(+-)-methylphenidate in striatum are localized to dopaminergic nerve terminals, and may be associated with the dopamine transport complex. (orig.)

  12. Parsing Heterogeneous Striatal Activity

    Directory of Open Access Journals (Sweden)

    Kae Nakamura

    2017-05-01

    Full Text Available The striatum is an input channel of the basal ganglia and is well known to be involved in reward-based decision making and learning. At the macroscopic level, the striatum has been postulated to contain parallel functional modules, each of which includes neurons that perform similar computations to support selection of appropriate actions for different task contexts. At the single-neuron level, however, recent studies in monkeys and rodents have revealed heterogeneity in neuronal activity even within restricted modules of the striatum. Looking for generality in the complex striatal activity patterns, here we briefly survey several types of striatal activity, focusing on their usefulness for mediating behaviors. In particular, we focus on two types of behavioral tasks: reward-based tasks that use salient sensory cues and manipulate outcomes associated with the cues; and perceptual decision tasks that manipulate the quality of noisy sensory cues and associate all correct decisions with the same outcome. Guided by previous insights on the modular organization and general selection-related functions of the basal ganglia, we relate striatal activity patterns on these tasks to two types of computations: implementation of selection and evaluation. We suggest that a parsing with the selection/evaluation categories encourages a focus on the functional commonalities revealed by studies with different animal models and behavioral tasks, instead of a focus on aspects of striatal activity that may be specific to a particular task setting. We then highlight several questions in the selection-evaluation framework for future explorations.

  13. No significant effects of single intravenous, single oral and subchronic oral administration of acetylcholinesterase inhibitors on striatal [123I]FP-CIT binding in rats

    NARCIS (Netherlands)

    Knol, R. J. J.; de Bruin, K.; van Eck-Smit, B. L. F.; Booij, J.

    2008-01-01

    PURPOSE: [(123)I]FP-CIT SPECT is a valuable diagnostic tool to discriminate Lewy body dementia from Alzheimer's dementia. To date, however, it is uncertain whether the frequently used acetylcholinesterase inhibitors (AChEIs) by demented patients, have an effect on [(123)I]FP-CIT binding to dopamine

  14. Continuous improvement: A win... win process

    International Nuclear Information System (INIS)

    Lawrence, T.; Wichert, A.

    1993-01-01

    Implementing a continuous improvement (CI) process within PanCanadian's oil and gas production operations might have been a simple assignment if one were not also trying to capture the hearts and imaginations of the people in a changing work environment. Meeting the challenge is resulting in big payoffs to both the organization and its people. The plan used within the Company's Production Division to successfully introduce the CI process is discussed. A brief insight is provided on the process philosophy, with emphasis placed on planning, training and coaching used to launch the process. Also reviewed at length are the impediments to change and the challenges faced when changing an organization's culture. In a CI work environment, the supervisor's traditional role changes from one of monitoring and controlling to one of inspiring, motivating and leading people by communicating a clear vision. Employees at all levels in the work environment are organized into teams and armed with a good working knowledge of the problem solving tools which allow them to pursue and implement improvement initiatives. The outcome of the process is an ongoing 'win-win' situation for both the Company and its people. Employees are gaining more trust, eliminating job irritants and enjoying their work more in a team environment. The Company is winning through increased production, improved safety and reduced operating expenses, thanks to many innovative ideas which the employees have implemented. 4 refs

  15. Successful Undergraduate Research: Creating Win-Win-Win

    Science.gov (United States)

    Guswa, A. J.; Rhodes, A. L.

    2003-12-01

    Undergraduate involvement in research has the potential to advance science, enhance education, strengthen the research community, and raise general awareness of the importance and impact of scientific understanding. Rather than being competing objectives, these goals are synergistic. Effective research experiences are those that create win-win-win situations: benefits to the student, benefits to the project, and benefits to the scientific community. When structured appropriately, undergraduate research fits into a learner-centered paradigm that puts emphasis on student learning, rather than instructor teaching. Under such a paradigm the student and professor learn together, constructing knowledge by integrating information with critical-thinking and problem-solving skills, and use this knowledge to address issues in real-life contexts. Creating such a learning environment requires that the professor be vested in the outcome of the research, that the student take a meta-cognitive approach to the project and work at a level appropriate to her abilities, and that the student understand how her contribution fits into the project and the larger field. All of these factors lead to greater independence, confidence, and productivity on the part of the student. By providing undergraduates with these experiences, we introduce not only future scientists but also non-scientists to the excitement of discovery and the value of scientific research. Currently, we involve undergraduates in our research on the hydrology and geochemistry of a tropical montane cloud forest in Monteverde, Costa Rica. At the start of each student's involvement, we provide her with the big picture: our project goals, the relevant social issues, and the importance of watershed research. Each student then articulates her own educational and project objectives. Together, we choose tasks that match her skills and interests with our scholarly work. Specific activities range from literature review to

  16. Halogenated mazindol analogs as potential inhibitors of the cocaine binding site at the dopamine transporter.

    Science.gov (United States)

    Houlihan, W J; Boja, J W; Parrino, V A; Kopajtic, T A; Kuhar, M J

    1996-12-06

    A series of halogenated (F, Cl, Br, I), pyrimido and diazepino homologs of mazindol were prepared and evaluated for their ability to displace [3H]WIN 35,428 binding and to inhibit uptake of [3H]dopamine (DA) in rat striatal tissue. All of the compounds except for the 2'-chloro (6) and 2'-bromo (16) analogs of mazindol displaced [3H]WIN 35,428 binding and inhibited [3H]DA uptake more effectively than (R)-cocaine. Structure-activity studies indicated that best inhibition of [3H]WIN 35,428 binding occurred in the imidazo series with compounds containing one or two Cl or Br atoms in the 3'- or 4'-position of the free phenyl group. Replacement of the imidazo ring by a pyrimido or diazepino ring enhanced binding inhibition. The most potent inhibitors of [3H]WIN 35,428 binding and [3H]DA uptake were 6-(3'-chlorophenyl)-2,3,4,6-tetrahydropyrimido[2,1-alpha]isoind ol-6-ol (23; IC50 1.0 nM; 8 x mazindol) and 7-(3',4'-dichlorophenyl)-2,3,4,5-tetrahydro-7H-diazepino[2,1-alpha ]isoindol-7-ol (28; IC50 0.26 nM; 32 x mazindol), respectively. No significant differences was found between binding and uptake inhibition. Mazindol and the pyrimido and diazepino homologs 24 and 27 showed a selectivity for the DA uptake over the serotonin (5-HT) uptake site of 5-, 250-, and 465-fold, respectively, and displayed weak or no affinity for a variety of neurotransmitter receptor sites.

  17. Continuous improvement: A win-win process

    International Nuclear Information System (INIS)

    Lawrence, T.M.; Wichert, A.

    1992-01-01

    The strategies used within PanCanadian Petroleum Limited's production division to successfully introduce the continuous improvement (CI) process are discussed. Continuous improvement is an operating philosophy and management style which allows all employees to participate in and improve the way an organization performs its day-to-day business. In the CI work environment the supervisor's traditional role changes from one of monitoring and controlling, to one of inspiring, motivating and leading people by communicating a clear vision. Employees at all levels in the work environment are organized into teams and armed with a good working knowledge of the problem-solving tools which allow them to pursue and implement improvement initiatives. The outcome of the process is an ongoing win-win situation for both PanCanadian and its people. Employees are gaining more trust, eliminating job irritants, and enjoying their work in a team environment. The company is benefiting through increased production, improved safety and reduced operating expenses, thanks to the many innovative ideas introduced by employees. 4 refs

  18. The Importance of Teaching a Win-Win Philosophy.

    Science.gov (United States)

    Brainard, Alan J.

    Most people are raised in a traditional environment which teaches that someone-winning implies that someone-loses. However, psychology and the examples provided in the Watergate scandal demonstrate that such a philosophy is neither productive nor beneficial. A "win-win" philosophy of cooperation, not competition, is needed for…

  19. Award Winning Science Projects.

    Science.gov (United States)

    Showalter, Victor M.; Slesnick, Irwin L.

    This is a collection of reports of student award winning science projects that have appeared in "The Science Teacher." Grade levels 7-12 are represented with projects categorized as follows: biology, chemistry and physics, earth-space science, and miscellaneous. In each section the abstracts are arranged in order of increasing complexity…

  20. Huntington's Disease and Striatal Signaling

    Directory of Open Access Journals (Sweden)

    Emmanuel eRoze

    2011-08-01

    Full Text Available Huntington’s Disease (HD is the most frequent neurodegenerative disease caused by an expansion of polyglutamines (CAG. The main clinical manifestations of HD are chorea, cognitive impairment and psychiatric disorders. The transmission of HD is autosomal dominant with a complete penetrance. HD has a single genetic cause, a well-defined neuropathology, and informative pre-manifest genetic testing of the disease is available. Striatal atrophy begins as early as 15 years before disease onset and continues throughout the period of manifest illness. Therefore, patients could theoretically benefit from therapy at early stages of the disease. One important characteristic of HD is the striatal vulnerability to neurodegeneration, despite similar expression of the protein in other brain areas. Aggregation of the mutated Huntingtin (HTT, impaired axonal transport, excitotoxicity, transcriptional dysregulation as well as mitochondrial dysfunction and energy deficits, are all part of the cellular events that underlie neuronal dysfunction and striatal death. Among these non-exclusive mechanisms, an alteration of striatal signaling is thought to orchestrate the downstream events involved in the cascade of striatal dysfunction.

  1. Winning hearts and minds

    International Nuclear Information System (INIS)

    Drulia, M.R.

    1999-01-01

    'The greatest problem in communication is the illusion that it has been accomplished' (George Bernard Shaw). Over the past few decades we have seen major shifts in opinion as to what makes a business successful. The 1950's and 1960's saw a production focus whilst the 1970's and 1980's saw progressive change towards quality and 'customer is king' as key business drivers. A popular view now suggests that the next step change will be towards internal marketing, based on the concept that, in the future, winning employee support will be seen as the single biggest contributor to driving business performances. In summary, to win hearts and minds you must understand the needs of your audience, the intent of your communication activity, adopt a suitable style and match your deeds to your words

  2. 2014 WIN3 Workshop

    CERN Document Server

    Long, Ling; Pries, Rachel; Stange, Katherine

    2016-01-01

    Exploring the interplay between deep theory and intricate computation, this volume is a compilation of research and survey papers in number theory, written by members of the Women In Numbers (WIN) network, principally by the collaborative research groups formed at Women In Numbers 3, a conference at the Banff International Research Station in Banff, Alberta, on April 21-25, 2014. The papers span a wide range of research areas: arithmetic geometry; analytic number theory; algebraic number theory; and applications to coding and cryptography. The WIN conference series began in 2008, with the aim of strengthening the research careers of female number theorists. The series introduced a novel research-mentorship model: women at all career stages, from graduate students to senior members of the community, joined forces to work in focused research groups on cutting-edge projects designed and led by experienced researchers. The goals for Women In Numbers 3 were to establish ambitious new collaborations between women i...

  3. Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging.

  4. When winning is everything.

    Science.gov (United States)

    Malhotra, Deepak; Ku, Gillian; Murnighan, J Keith

    2008-05-01

    In the heat of competition, executives can easily become obsessed with beating their rivals. This adrenaline-fueled emotional state, which the authors call competitive arousal, often leads to bad decisions. Managers can minimize the potential for competitive arousal and the harm it can inflict by avoiding certain types of interaction and targeting the causes of a win-at-all-costs approach to decision making. Through an examination of companies such as Boston Scientific and Paramount, and through research on auctions, the authors identified three principal drivers of competitive arousal: intense rivalry, especially in the form of one-on-one competitions; time pressure, found in auctions and other bidding situations, for example; and being in the spotlight--that is, working in the presence of an audience. Individually, these factors can seriously impair managerial decision making; together, their consequences can be dire, as evidenced by many high-profile business disasters. It's not possible to avoid destructive competitions and bidding wars completely. But managers can help prevent competitive arousal by anticipating potentially harmful competitive dynamics and then restructuring the deal-making process. They can also stop irrational competitive behavior from escalating by addressing the causes of competitive arousal. When rivalry is intense, for instance, managers can limit the roles of those who feel it most. They can reduce time pressure by extending or eliminating arbitrary deadlines. And they can deflect the spotlight by spreading the responsibility for critical competitive decisions among team members. Decision makers will be most successful when they focus on winning contests in which they have a real advantage--and take a step back from those in which winning exacts too high a cost.

  5. Win-win Imageries in a Soap Bubble World

    DEFF Research Database (Denmark)

    Ekman, Susanne

    2015-01-01

    This article explores the imagery and notions of personhood underlying the willingness to undertake extreme work among creative knowledge workers. The core argument is that extreme work is informed by pervasive win-win fantasies which can be recognized in a number of current organizational trends...

  6. Imaging of striatal dopamine transporters in rat brain with single pinhole SPECT and co-aligned MRI is highly reproducible

    International Nuclear Information System (INIS)

    Booij, Jan; Bruin, Kora de; Win, Maartje M.L. de; Lavini, Cristina Mphil; Heeten, Gerard J. den; Habraken, Jan

    2003-01-01

    A recently developed pinhole high-resolution SPECT system was used to measure striatal to non-specific binding ratios in rats (n = 9), after injection of the dopamine transporter ligand 123 I-FP-CIT, and to assess its test/retest reproducibility. For co-alignment purposes, the rat brain was imaged on a 1.5 Tesla clinical MRI scanner using a specially developed surface coil. The SPECT images showed clear striatal uptake. On the MR images, cerebral and extra-cerebral structures could be easily delineated. The mean striatal to non-specific [ 123 I]FP-CIT binding ratios of the test/retest studies were 1.7 ± 0.2 and 1.6 ± 0.2, respectively. The test/retest variability was approximately 9%. We conclude that the assessment of striatal [ 123 I]FP-CIT binding ratios in rats is highly reproducible

  7. Wins, winning and winners: the commercial advertising of lottery gambling.

    Science.gov (United States)

    McMullan, John L; Miller, Delthia

    2009-09-01

    This study analyzed a sample of 920 lottery ads that were placed or played in Atlantic Canada from January 2005 to December 2006. A content analysis, involving quantitative and qualitative techniques, was conducted to examine the design features, exposure profiles and focal messages of these ads and to explore the connections between lottery advertising and consumer culture. We found that there was an "ethos of winning" in these commercials that provided the embedded words, signs, myths, and symbols surrounding lottery gambling and conveyed a powerful imagery of plentitude and certitude in a world of potential loss where there was little reference to the actual odds of winning. The tangible and emotional qualities in the ads were especially inviting to young people creating a positive orientation to wins, winning and winners, and lottery products that, in turn, reinforced this form of gambling as part of youthful consumption practices. We concluded that enticing people with the prospects of huge jackpots, attractive consumer goods and easy wins, showcasing top prize winners, and providing dubious depictions that winning is life-changing was narrow and misleading and exploited some of the factors associated with at-risk gambling.

  8. Striatal mechanisms underlying movement, reinforcement, and punishment.

    Science.gov (United States)

    Kravitz, Alexxai V; Kreitzer, Anatol C

    2012-06-01

    Direct and indirect pathway striatal neurons are known to exert opposing control over motor output. In this review, we discuss a hypothetical extension of this framework, in which direct pathway striatal neurons also mediate reinforcement and reward, and indirect pathway neurons mediate punishment and aversion.

  9. Striatal Mechanisms Underlying Movement, Reinforcement, and Punishment

    OpenAIRE

    Kravitz, Alexxai V.; Kreitzer, Anatol C.

    2012-01-01

    Direct and indirect pathway striatal neurons are known to exert opposing control over motor output. In this review, we discuss a hypothetical extension of this framework, in which direct pathway striatal neurons also mediate reinforcement and reward, and indirect pathway neurons mediate punishment and aversion.

  10. In the winning mood

    Directory of Open Access Journals (Sweden)

    Marieke de Vries

    2008-01-01

    Full Text Available The present research aimed to test the role of mood in the Iowa Gambling Task (IGT; Bechara et al., 1994. In the IGT, participants can win or lose money by picking cards from four different decks. They have to learn by experience that two decks are overall advantageous and two decks are overall disadvantageous. Previous studies have shown that at an early stage in this card-game, players begin to display a tendency towards the advantageous decks. Subsequent research suggested that at this stage, people base their decisions on conscious gut feelings (Wagar and Dixon, 2006. Based on empirical evidence for the relation between mood and cognitive processing-styles, we expected and consistently found that, compared to a negative mood state, reported and induced positive mood states increased this early tendency towards advantageous decks. Our results provide support for the idea that a positive mood causes stronger reliance on affective signals in decision-making than a negative mood.

  11. Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease

    NARCIS (Netherlands)

    van Oostrom, JCH; Maguire, RP; Verschuuren-Bemelmans, CC; van der Duin, LV; Pruim, J; Roos, RAC; Leenders, KL

    2005-01-01

    Among 27 preclinical carriers of the Huntington disease mutation (PMC), the authors found normal striatal values for MRI volumetry in 88% and for fluorodesoxyglucose PET metabolic index in 67%. Raclopride PET binding potential (RAC-BP) was decreased in 50% and correlated with increases in the

  12. Dopamine denervation does not alter in vivo 3H-spiperone binding in rat striatum: implications for external imaging of dopamine receptors in Parkinson's disease

    International Nuclear Information System (INIS)

    Bennett, J.P. Jr.; Wooten, G.F.

    1986-01-01

    Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased 3 H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic compounds. After intravenous 3 H-spiperone ( 3 H-SP) administration to rats with unilateral nigral lesions, we found no differences in accumulation of total or particulate-bound 3 H-SP in dopamine-denervated compared with intact striata. 3 H-SP in vivo binds to less than 10% of striatal sites labeled by 3 H-SP incubated with striatal particulate preparations in vitro. Quantitative autoradiography of 3 H-SP binding to striatal sections in vitro also failed to reveal any effects of dopamine denervation. 3 H-SP bound to striatal sites in vivo dissociates more slowly than that bound to striatal particulate preparations labeled in vitro. Striatal binding properties of 3 H-SP administered in vivo are quite different from the same kinetic binding parameters estimated in vitro using crude membrane preparations of striatum. In addition, striatal binding of in vivo-administered 3H-SP is not affected by prior lesion of the substantia nigra, which results in profound ipsilateral striatal dopamine depletion. Thus, behavioral supersensitivity to dopaminergic compounds may not be associated with altered striatal binding properties for dopamine receptor ligands in vivo

  13. Eastern countries - WIN activity review

    International Nuclear Information System (INIS)

    Stiopol, Mihaela

    1998-01-01

    Women can play this important role in informing people about nuclear energy. WIN is a world-wide association of women working professionally in the fields of nuclear energy and radiation application who want to devote their time to public information. The main goal of the WIN is to establish an objective and effective communication with the public through educational programmes, information exchange and arranging study visits. The membership includes women working in medicine and health care, in regulatory authorities, in industry and as independent researches at Universities. They want to contribute to objectively informing the public by making presentation, discussing and giving information materials on subjects such as; radiation, radioactivity and health effects medical applications nuclear energy nuclear power plants and their safety nuclear and environment uranium mining radiation protection energy sustainable development WIN is also open to men, supporting the goals of WIN. The intention of this paper was to underline the main aspects which reflect WIN activity in some Eastern and Central countries. There are common features and also specific elements for each country. But the goal is the same: to assure an effective and a real information of the public related to the nuclear field

  14. Win at Work! The Everybody Wins Approach to Conflict Resolution

    CERN Document Server

    Katz, Diane

    2010-01-01

    Proven techniques for resolving workplace conflicts. After years of seeing clients struggling and their businesses suffering with destructive conflicts, Diane Katz developed The Working Circle, a step-by-step process that helps everyone in business resolve conflict in a non-confrontational, creative, collaborative way. Win at Work! provides you with a no-nonsense guide based on real-life examples of people at pivotal points in their careers. Filled with practical wisdom, it reveals how you can move around the roadblocks that, if left unattanded, can stop you in your tracks. Win at Work! also h

  15. Frances Allen Wins Turing Award

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 12; Issue 8. Frances Allen Wins Turing Award. Priti Shankar. Article-in-a-Box Volume 12 Issue 8 August 2007 pp 5-5. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/012/08/0005-0005. Author Affiliations.

  16. Frances Allen Wins Turing Award

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 12; Issue 8. Frances Allen Wins Turing Award. Priti Shankar. Article-in-a-Box Volume 12 Issue 8 August 2007 pp ... Author Affiliations. Priti Shankar1. Department of Computer Science and Automation, Indian Institute of Science, Bangalore 560 012, India ...

  17. Just watching the game ain’t enough: Striatal fMRI reward responses to successes and failures in a video game during active and vicarious playing

    Directory of Open Access Journals (Sweden)

    Jari eKätsyri

    2013-06-01

    Full Text Available Although the multimodal stimulation provided by modern audiovisual video games is pleasing by itself, the rewarding nature of video game playing depends critically also on the players’ active engagement in the gameplay. The extent to which active engagement influences dopaminergic brain reward circuit responses remains unsettled. Here we show that striatal reward circuit responses elicited by successes (wins and failures (losses in a video game are stronger during active than vicarious gameplay. Eleven healthy males both played a competitive first-person tank shooter game (active playing and watched a pre-recorded gameplay video (vicarious playing while their hemodynamic brain activation was measured with 3-tesla functional magnetic resonance imaging (fMRI. Wins and losses were paired with symmetrical monetary rewards and punishments during active and vicarious playing so that the external reward context remained identical during both conditions. Brain activation was stronger in the orbitomedial prefrontal cortex (omPFC during winning than losing, both during active and vicarious playing conditions. In contrast, both wins and losses suppressed activations in the midbrain and striatum during active playing; however, the striatal suppression, particularly in the anterior putamen, was more pronounced during loss than win events. Sensorimotor confounds related to joystick movements did not account for the results. Self-ratings indicated losing to be more unpleasant during active than vicarious playing. Our findings demonstrate striatum to be selectively sensitive to self-acquired rewards, in contrast to frontal components of the reward circuit that process both self-acquired and passively received rewards. We propose that the striatal responses to repeated acquisition of rewards that are contingent on game related successes contribute to the motivational pull of video-game playing.

  18. Just watching the game ain't enough: striatal fMRI reward responses to successes and failures in a video game during active and vicarious playing.

    Science.gov (United States)

    Kätsyri, Jari; Hari, Riitta; Ravaja, Niklas; Nummenmaa, Lauri

    2013-01-01

    Although the multimodal stimulation provided by modern audiovisual video games is pleasing by itself, the rewarding nature of video game playing depends critically also on the players' active engagement in the gameplay. The extent to which active engagement influences dopaminergic brain reward circuit responses remains unsettled. Here we show that striatal reward circuit responses elicited by successes (wins) and failures (losses) in a video game are stronger during active than vicarious gameplay. Eleven healthy males both played a competitive first-person tank shooter game (active playing) and watched a pre-recorded gameplay video (vicarious playing) while their hemodynamic brain activation was measured with 3-tesla functional magnetic resonance imaging (fMRI). Wins and losses were paired with symmetrical monetary rewards and punishments during active and vicarious playing so that the external reward context remained identical during both conditions. Brain activation was stronger in the orbitomedial prefrontal cortex (omPFC) during winning than losing, both during active and vicarious playing. In contrast, both wins and losses suppressed activations in the midbrain and striatum during active playing; however, the striatal suppression, particularly in the anterior putamen, was more pronounced during loss than win events. Sensorimotor confounds related to joystick movements did not account for the results. Self-ratings indicated losing to be more unpleasant during active than vicarious playing. Our findings demonstrate striatum to be selectively sensitive to self-acquired rewards, in contrast to frontal components of the reward circuit that process both self-acquired and passively received rewards. We propose that the striatal responses to repeated acquisition of rewards that are contingent on game related successes contribute to the motivational pull of video-game playing.

  19. Repeated cocaine administration results in supersensitivity of striatal D-2 dopamine autoreceptors to pergolide

    International Nuclear Information System (INIS)

    Dwoskin, L.P.; Peris, J.; Yasuda, R.P.; Philpott, K.; Zahniser, N.R.

    1988-01-01

    Groups of rats administered cocaine-HCl (10 mg/kg, i.p.) or saline either acutely or once daily for 8 or 14 days were killed 24 hrs after the last dose. In striatal slices prelabelled with [ 3 H]DA, modulation of [ 3 H]-overflow by pergolide was used to measure D-2 autoreceptor activity. Compared to the contemporaneous control group pergolide produced a greater inhibition only in striatal slices from rats treated repeatedly with cocaine. In radioligand binding studies using striatal membranes from control rats, pergolide had a 500-fold greater affinity for the D-2, as opposed to the D-1, dopamine (DA) receptor subtype. These results indicate that repeated treatment with cocaine produces supersensitive striatal D-2 release-modulating autoreceptors consistent with a compensatory change to diminish the effect of elevated synaptic concentrations of DA produced by cocaine. In contrast, supersensitivity of D-2 receptors was not detected in [ 3 H]spiperone binding assays. 31 references, 2 figures, 1 table

  20. Quantitation of specific binding ratio in 123I-FP-CIT SPECT: accurate processing strategy for cerebral ventricular enlargement with use of 3D-striatal digital brain phantom.

    Science.gov (United States)

    Furuta, Akihiro; Onishi, Hideo; Amijima, Hizuru

    2018-04-26

    This study aimed to evaluate the effect of ventricular enlargement on the specific binding ratio (SBR) and to validate the cerebrospinal fluid (CSF)-Mask algorithm for quantitative SBR assessment of 123 I-FP-CIT single-photon emission computed tomography (SPECT) images with the use of a 3D-striatum digital brain (SDB) phantom. Ventricular enlargement was simulated by three-dimensional extensions in a 3D-SDB phantom comprising segments representing the striatum, ventricle, brain parenchyma, and skull bone. The Evans Index (EI) was measured in 3D-SDB phantom images of an enlarged ventricle. Projection data sets were generated from the 3D-SDB phantoms with blurring, scatter, and attenuation. Images were reconstructed using the ordered subset expectation maximization (OSEM) algorithm and corrected for attenuation, scatter, and resolution recovery. We bundled DaTView (Southampton method) with the CSF-Mask processing software for SBR. We assessed SBR with the use of various coefficients (f factor) of the CSF-Mask. Specific binding ratios of 1, 2, 3, 4, and 5 corresponded to SDB phantom simulations with true values. Measured SBRs > 50% that were underestimated with EI increased compared with the true SBR and this trend was outstanding at low SBR. The CSF-Mask improved 20% underestimates and brought the measured SBR closer to the true values at an f factor of 1.0 despite an increase in EI. We connected the linear regression function (y = - 3.53x + 1.95; r = 0.95) with the EI and f factor using root-mean-square error. Processing with CSF-Mask generates accurate quantitative SBR from dopamine transporter SPECT images of patients with ventricular enlargement.

  1. Striatal cholinergic interneuron regulation and circuit effects

    Directory of Open Access Journals (Sweden)

    Sean Austin Lim

    2014-10-01

    Full Text Available The striatum plays a central role in motor control and motor learning. Appropriate responses to environmental stimuli, including pursuit of reward or avoidance of aversive experience all require functional striatal circuits. These pathways integrate synaptic inputs from limbic and cortical regions including sensory, motor and motivational information to ultimately connect intention to action. Although many neurotransmitters participate in striatal circuitry, one critically important player is acetylcholine (ACh. Relative to other brain areas, the striatum contains exceptionally high levels of ACh, the enzymes that catalyze its synthesis and breakdown, as well as both nicotinic and muscarinic receptor types that mediate its postsynaptic effects. The principal source of striatal ACh is the cholinergic interneuron (ChI, which comprises only about 1-2% of all striatal cells yet sends dense arbors of projections throughout the striatum. This review summarizes recent advances in our understanding of the factors affecting the excitability of these neurons through acute effects and long term changes in their synaptic inputs. In addition, we discuss the physiological effects of ACh in the striatum, and how changes in ACh levels may contribute to disease states during striatal dysfunction.

  2. Huntington’s Disease and Striatal Signaling

    Science.gov (United States)

    Roze, Emmanuel; Cahill, Emma; Martin, Elodie; Bonnet, Cecilia; Vanhoutte, Peter; Betuing, Sandrine; Caboche, Jocelyne

    2011-01-01

    Huntington’s Disease (HD) is the most frequent neurodegenerative disease caused by an expansion of polyglutamines (CAG). The main clinical manifestations of HD are chorea, cognitive impairment, and psychiatric disorders. The transmission of HD is autosomal dominant with a complete penetrance. HD has a single genetic cause, a well-defined neuropathology, and informative pre-manifest genetic testing of the disease is available. Striatal atrophy begins as early as 15 years before disease onset and continues throughout the period of manifest illness. Therefore, patients could theoretically benefit from therapy at early stages of the disease. One important characteristic of HD is the striatal vulnerability to neurodegeneration, despite similar expression of the protein in other brain areas. Aggregation of the mutated Huntingtin (HTT), impaired axonal transport, excitotoxicity, transcriptional dysregulation as well as mitochondrial dysfunction, and energy deficits, are all part of the cellular events that underlie neuronal dysfunction and striatal death. Among these non-exclusive mechanisms, an alteration of striatal signaling is thought to orchestrate the downstream events involved in the cascade of striatal dysfunction. PMID:22007160

  3. Construction of the subtracted cDNA library of striatal neurons treated with long-term morphine.

    Science.gov (United States)

    Bai, Bo; Liu, Hai-qing; Chen, Jing; Li, Ya-lin; Du, Hui; Lu, Hai; Yu, Peng-li

    2011-03-01

    To construct a morphine tolerance model in primarily cultured striatal neurons, and screen the differentially expressed genes in this model using suppression subtractive hybridization (SSH). Sbtracted cDNA libraries were constructed using SSH from normal primarily cultured striatal neurons and long-term morphine treated striatal neurons (10-5 mol/L for 72 hours). To check reliability of the cell culture model, RT-PCR was performed to detect the cAMP-responsive element-binding protein (CREB) mRNA expression. The subtracted clones were prescreened by PCR. The clones containing inserted fragments from forward libraries were sequenced and submitted to GenBank for homology analysis. And the expression levels of genes of interest were confirmed by RT-PCR. Results CREB mRNA expression showed a significant increase in morphine treated striatal neurons (62.85 ± 1.98) compared with normal striatal neurons (28.43 ± 1.46, P library of striatal neurons treated with long-term morphine is constructed. Mtch1 and Akt1 might be the candidate genes for the development of morphine tolerance.

  4. Adenosine Receptor Heteromers and their Integrative Role in Striatal Function

    Directory of Open Access Journals (Sweden)

    Sergi Ferré

    2007-01-01

    Full Text Available By analyzing the functional role of adenosine receptor heteromers, we review a series of new concepts that should modify our classical views of neurotransmission in the central nervous system (CNS. Neurotransmitter receptors cannot be considered as single functional units anymore. Heteromerization of neurotransmitter receptors confers functional entities that possess different biochemical characteristics with respect to the individual components of the heteromer. Some of these characteristics can be used as a “biochemical fingerprint” to identify neurotransmitter receptor heteromers in the CNS. This is exemplified by changes in binding characteristics that are dependent on coactivation of the receptor units of different adenosine receptor heteromers. Neurotransmitter receptor heteromers can act as “processors” of computations that modulate cell signaling, sometimes critically involved in the control of pre- and postsynaptic neurotransmission. For instance, the adenosine A1-A2A receptor heteromer acts as a concentration-dependent switch that controls striatal glutamatergic neurotransmission. Neurotransmitter receptor heteromers play a particularly important integrative role in the “local module” (the minimal portion of one or more neurons and/or one or more glial cells that operates as an independent integrative unit, where they act as processors mediating computations that convey information from diverse volume-transmitted signals. For instance, the adenosine A2A-dopamine D2 receptor heteromers work as integrators of two different neurotransmitters in the striatal spine module.

  5. Striatal μ-opioid receptor availability predicts cold pressor pain threshold in healthy human subjects

    DEFF Research Database (Denmark)

    Hagelberg, Nora; Aalto, Sargo; Tuominen, Lauri

    2012-01-01

    the potential associations between μ-opioid receptor BP(ND) and psychophysical measures. The results show that striatal μ-opioid receptor BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance or tactile sensitivity. This finding suggests that striatal μ-opioid receptor density......Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding...... at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects...

  6. Environmental enrichment enhances synaptic plasticity by internalization of striatal dopamine transporters

    Science.gov (United States)

    Kim, Myung-Sun; Yu, Ji Hea; Kim, Chul Hoon; Choi, Jae Yong; Seo, Jung Hwa; Lee, Min-Young; Yi, Chi Hoon; Choi, Tae Hyun; Ryu, Young Hoon; Lee, Jong Eun; Lee, Bae Hwan; Kim, Hyongbum

    2015-01-01

    Environmental enrichment (EE) with a complex combination of physical, cognitive and social stimulations enhances synaptic plasticity and behavioral function. However, the mechanism remains to be elucidated in detail. We aimed to investigate dopamine-related synaptic plasticity underlying functional improvement after EE. For this, six-week-old CD-1 mice were randomly allocated to EE or standard conditions for two months. EE significantly enhanced behavioral functions such as rotarod and ladder walking tests. In a [18F]FPCIT positron emission tomography scan, binding values of striatal DAT were significantly decreased approximately 18% in the EE mice relative to the control mice. DAT inhibitor administrated to establish the relationship of the DAT down-regulation to the treatment effects also improved rotarod performances, suggesting that DAT inhibition recapitulated EE-mediated treatment benefits. Next, EE-induced internalization of DAT was confirmed using a surface biotinylation assay. In situ proximity ligation assay and immunoprecipitation demonstrated that EE significantly increased the phosphorylation of striatal DAT as well as the levels of DAT bound with protein kinase C (PKC). In conclusion, we suggest that EE enables phosphorylation of striatal DAT via a PKC-mediated pathway and causes DAT internalization. This is the first report to suggest an EE-mediated mechanism of synaptic plasticity by internalization of striatal DAT. PMID:26661218

  7. Reduced striatal dopamine D2/3 receptor availability in Body Dysmorphic Disorder.

    Science.gov (United States)

    Vulink, Nienke C; Planting, Robin S; Figee, Martijn; Booij, Jan; Denys, Damiaan

    2016-02-01

    Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive Compulsive Disorder (OCD), we hypothesized that the dopamine D2/3 receptor availability in the striatum will be lower in patients with BDD in comparison to healthy subjects. Striatal dopamine D2/3 receptor Binding Potential (BPND) was examined in 12 drug-free BDD patients and 12 control subjects pairwise matched by age, sex, and handedness using [(123)I]iodobenzamide Single Photon Emission Computed Tomography (SPECT; bolus/constant infusion technique). Regions of interest were the caudate nucleus and the putamen. BPND was calculated as the ratio of specific striatal to binding in the occipital cortex (representing nonspecific binding). Compared to controls, dopamine D2/3 receptor BPND was significantly lower in BDD, both in the putamen (p=0.017) and caudate nucleus (p=0.022). This study provides the first evidence of a disturbed dopaminergic system in BDD patients. Although previously BDD was classified as a separate disorder (somatoform disorder), our findings give pathophysiological support for the recent reclassification of BDD to the OCRD in DSM-5. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  8. WIN Chapters: Milestones and Future Plans

    Energy Technology Data Exchange (ETDEWEB)

    Castro, P.; Pelegrí, M.

    2015-07-01

    In this paper the WIN Chapters: milestones and future plans are presented. WIN-IAEA has rewarded-in the three last years - to Australia-2014, South-Africa-2013 and Sweden-2012. WIN-Global -specially WiN IAEA- can collaborate a lot with the CTBTO presenting the content of the Treaty on the Non-Proliferation of Nuclear Weapons actually increasing the signatory members in 2015. Historical decisions on NTP are already affecting WiN IAEA. The research reactors or high flux reactors are important in the field of medical applications and other future applications. In Australia women-scientist of OPAL, can become WiN. Between the OPAL applications there is a production of silicon plates to be used in laptops/mobiles. WIN-Europe activities related with the climatic change and with the academic promotion. 2015 is also a very important year due the celebration of 20th Anniversary of WIN-Spain; plans of this Chapter and Conferences of WIN-Global are presented. In addition there are women working in ITER, in some activities in the EU, China, India, Japan, South Korea, USA and Russia both in the academic (R+D) field and into the Industry. (Author)

  9. Opportunistic Cognitive Relaying: A Win-Win Spectrum Sharing Scheme

    Directory of Open Access Journals (Sweden)

    Luo Haiyan

    2010-01-01

    Full Text Available A cost-effective spectrum sharing architecture is proposed to enable the legacy noncognitive secondary system to coexist with the primary system. Specifically, we suggest to install a few intermediate nodes, namely, the cognitive relays, to conduct the spectrum sensing and coordinate the spectrum access. To achieve the goal of win-win between primary and secondary systems, the cognitive relay may act as a cooperator for both of them, and an Opportunistic Cognitive Relaying (OCR scheme is specially devised. In this scheme, the cognitive relay opportunistically switches among three different working modes, that is, Relay for Primary Link (RPL, Relay for Secondary Link (RSL, or Relay for Neither of the Links (RNL, respectively, based on the channel-dependent observation of both systems. In addition, the transmit power for cognitive relay and secondary transmitter in each mode are optimally determined by maximizing the transmission rate of secondary system while keeping or even reducing the outage probability of primary system. Simulation results validate the efficiency of the proposed spectrum sharing scheme.

  10. Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

    Science.gov (United States)

    Bossong, Matthijs G; Mehta, Mitul A; van Berckel, Bart N M; Howes, Oliver D; Kahn, René S; Stokes, Paul R A

    2015-08-01

    Elevated dopamine function is thought to play a key role in both the rewarding effects of addictive drugs and the pathophysiology of schizophrenia. Accumulating epidemiological evidence indicates that cannabis use is a risk factor for the development of schizophrenia. However, human neurochemical imaging studies that examined the impact of ∆9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, on striatal dopamine release have provided inconsistent results. The objective of this study is to assess the effect of a THC challenge on human striatal dopamine release in a large sample of healthy participants. We combined human neurochemical imaging data from two previous studies that used [(11)C]raclopride positron emission tomography (PET) (n = 7 and n = 13, respectively) to examine the effect of THC on striatal dopamine neurotransmission in humans. PET images were re-analysed to overcome differences in PET data analysis. THC administration induced a significant reduction in [(11)C]raclopride binding in the limbic striatum (-3.65 %, from 2.39 ± 0.26 to 2.30 ± 0.23, p = 0.023). This is consistent with increased dopamine levels in this region. No significant differences between THC and placebo were found in other striatal subdivisions. In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse. This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.

  11. Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment.

    Science.gov (United States)

    Robertson, Chelsea L; Ishibashi, Kenji; Chudzynski, Joy; Mooney, Larissa J; Rawson, Richard A; Dolezal, Brett A; Cooper, Christopher B; Brown, Amira K; Mandelkern, Mark A; London, Edythe D

    2016-05-01

    Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BPND)) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n=10) or one that received equal-time health education training (n=9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [(18)F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BPND. At baseline, striatal D2/D3 BPND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BPND, whereas those in the education group did not. There were no changes in D2/D3 BPND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.

  12. The basal ganglia matching tools package for striatal uptake semi-quantification: description and validation

    International Nuclear Information System (INIS)

    Calvini, Piero; Rodriguez, Guido; Nobili, Flavio; Inguglia, Fabrizio; Mignone, Alessandro; Guerra, Ugo P.

    2007-01-01

    To design a novel algorithm (BasGan) for automatic segmentation of striatal 123 I-FP-CIT SPECT. The BasGan algorithm is based on a high-definition, three-dimensional (3D) striatal template, derived from Talairach's atlas. A blurred template, obtained by convolving the former with a 3D Gaussian kernel (FWHM = 10 mm), approximates striatal activity distribution. The algorithm performs translations and scale transformation on the bicommissural aligned image to set the striatal templates with standard size in an appropriate initial position. An optimization protocol automatically performs fine adjustments in the positioning of blurred templates to best match the radioactive counts, and locates an occipital ROI for background evaluation. Partial volume effect correction is included in the process of uptake computation of caudate, putamen and background. Experimental validation was carried out by means of six acquisitions of an anthropomorphic striatal phantom. The BasGan software was applied to a first set of patients with Parkinson's disease (PD) versus patients affected by essential tremor. A highly significant correlation was achieved between true binding potential and measured 123 I activity from the phantom. 123 I-FP-CIT uptake was significantly lower in all basal ganglia in the PD group versus controls with both BasGan and a conventional ROI method used for comparison, but particularly with the former. Correlations with the motor UPDRS score were far more significant with the BasGan. The novel BasGan algorithm automatically performs the 3D segmentation of striata. Because co-registered MRI is not needed, it can be used by all nuclear medicine departments, since it is freely available on the Web. (orig.)

  13. Benzo- and cyclohexanomazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter.

    Science.gov (United States)

    Houlihan, William J; Ahmad, Umer F; Koletar, Judith; Kelly, Lawrence; Brand, Leonard; Kopajtic, Theresa A

    2002-09-12

    A series of mazindol (1), homomazindol (2), and bishomomazindol (3) derivatives with a benzo or cyclohexano ring fused at various sites were prepared as part of an SAR study to determine the effect of increased aliphatic and aromatic lipophilicity on selected in vitro assays used to identify potential cocaine-like and cocaine antagonism activity. Very good (IC(50) = 2-3 nM) inhibition of [(3)H] WIN 35,428 and [(125)I] RTI-55 binding on rat or guinea pig striatal membranes and HEK cells expressing cDNA for the human dopamine transporter (HEK-hDAT) was shown by the 8,9-benzomazindol 25 and 9,10-benzohomomazindol 28. All new compounds were weaker inhibitors of [(3)H] DA uptake in HEK-hDAT cells than 1 and 2. No improvement in the binding selectivity ratio (SERT/DAT and NET/DAT) was found when compared to 2. Compounds 25and 28 showed a considerable increase versus 1 in uptake/binding discrimination ratios at the DAT (311.0 and 182.1 vs 0.9), SERT (33.6 and 127.3 vs 1.9), and NET (7.3 and 10.0 vs 0.3).

  14. Bayesian modeling using WinBUGS

    CERN Document Server

    Ntzoufras, Ioannis

    2009-01-01

    A hands-on introduction to the principles of Bayesian modeling using WinBUGS Bayesian Modeling Using WinBUGS provides an easily accessible introduction to the use of WinBUGS programming techniques in a variety of Bayesian modeling settings. The author provides an accessible treatment of the topic, offering readers a smooth introduction to the principles of Bayesian modeling with detailed guidance on the practical implementation of key principles. The book begins with a basic introduction to Bayesian inference and the WinBUGS software and goes on to cover key topics, including: Markov Chain Monte Carlo algorithms in Bayesian inference Generalized linear models Bayesian hierarchical models Predictive distribution and model checking Bayesian model and variable evaluation Computational notes and screen captures illustrate the use of both WinBUGS as well as R software to apply the discussed techniques. Exercises at the end of each chapter allow readers to test their understanding of the presented concepts and all ...

  15. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    International Nuclear Information System (INIS)

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17β-estradiol (E 2 ) at both low (0.1 μg/kg) and high (20 μg/kg) doses confirmed its ability to increase the number of striatal 3 H-Spiperone ( 3 H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E 2 , to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity

  16. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17..beta..-estradiol (E/sub 2/) at both low (0.1 ..mu..g/kg) and high (20 ..mu..g/kg) doses confirmed its ability to increase the number of striatal /sup 3/H-Spiperone (/sup 3/H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E/sub 2/, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity.

  17. Striatal dopamine D2/3 receptor availability in treatment resistant depression.

    Directory of Open Access Journals (Sweden)

    Bart P de Kwaasteniet

    Full Text Available Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D(2/3 receptor (D2/3R binding has not been investigated in TRD subjects. We used [(123I]IBZM single photon emission computed tomography (SPECT to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group and 15 matched healthy controls. Results showed no significant difference (p = 0.75 in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics relative to TRD patients and healthy controls (p<0.001 but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs.

  18. Molecular Regulation of Striatal Development: A Review

    Directory of Open Access Journals (Sweden)

    A. E. Evans

    2012-01-01

    Full Text Available The central nervous system is composed of the brain and the spinal cord. The brain is a complex organ that processes and coordinates activities of the body in bilaterian, higher-order animals. The development of the brain mirrors its complex function as it requires intricate genetic signalling at specific times, and deviations from this can lead to brain malformations such as anencephaly. Research into how the CNS is specified and patterned has been studied extensively in chick, fish, frog, and mice, but findings from the latter will be emphasised here as higher-order mammals show most similarity to the human brain. Specifically, we will focus on the embryonic development of an important forebrain structure, the striatum (also known as the dorsal striatum or neostriatum. Over the past decade, research on striatal development in mice has led to an influx of new information about the genes involved, but the precise orchestration between the genes, signalling molecules, and transcription factors remains unanswered. We aim to summarise what is known to date about the tightly controlled network of interacting genes that control striatal development. This paper will discuss early telencephalon patterning and dorsal ventral patterning with specific reference to the genes involved in striatal development.

  19. Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kaasinen, Valtteri; Kinos, Maija; Joutsa, Juho [University of Turku and Turku University Hospital, Division of Clinical Neurosciences, Turku (Finland); University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Seppaenen, Marko [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); University of Turku and Turku University Hospital, Department of Clinical Physiology and Nuclear Medicine, Turku (Finland); Noponen, Tommi [University of Turku and Turku University Hospital, Department of Clinical Physiology and Nuclear Medicine, Turku (Finland)

    2014-10-15

    Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor. [{sup 123}I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates. Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p < 0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen. The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor. (orig.)

  20. Winning a competition predicts dishonest behavior.

    Science.gov (United States)

    Schurr, Amos; Ritov, Ilana

    2016-02-16

    Winning a competition engenders subsequent unrelated unethical behavior. Five studies reveal that after a competition has taken place winners behave more dishonestly than competition losers. Studies 1 and 2 demonstrate that winning a competition increases the likelihood of winners to steal money from their counterparts in a subsequent unrelated task. Studies 3a and 3b demonstrate that the effect holds only when winning means performing better than others (i.e., determined in reference to others) but not when success is determined by chance or in reference to a personal goal. Finally, study 4 demonstrates that a possible mechanism underlying the effect is an enhanced sense of entitlement among competition winners.

  1. De Novo Mutations in PDE10A Cause Childhood-Onset Chorea with Bilateral Striatal Lesions.

    Science.gov (United States)

    Mencacci, Niccolò E; Kamsteeg, Erik-Jan; Nakashima, Kosuke; R'Bibo, Lea; Lynch, David S; Balint, Bettina; Willemsen, Michèl A A P; Adams, Matthew E; Wiethoff, Sarah; Suzuki, Kazunori; Davies, Ceri H; Ng, Joanne; Meyer, Esther; Veneziano, Liana; Giunti, Paola; Hughes, Deborah; Raymond, F Lucy; Carecchio, Miryam; Zorzi, Giovanna; Nardocci, Nardo; Barzaghi, Chiara; Garavaglia, Barbara; Salpietro, Vincenzo; Hardy, John; Pittman, Alan M; Houlden, Henry; Kurian, Manju A; Kimura, Haruhide; Vissers, Lisenka E L M; Wood, Nicholas W; Bhatia, Kailash P

    2016-04-07

    Chorea is a hyperkinetic movement disorder resulting from dysfunction of striatal medium spiny neurons (MSNs), which form the main output projections from the basal ganglia. Here, we used whole-exome sequencing to unravel the underlying genetic cause in three unrelated individuals with a very similar and unique clinical presentation of childhood-onset chorea and characteristic brain MRI showing symmetrical bilateral striatal lesions. All individuals were identified to carry a de novo heterozygous mutation in PDE10A (c.898T>C [p.Phe300Leu] in two individuals and c.1000T>C [p.Phe334Leu] in one individual), encoding a phosphodiesterase highly and selectively present in MSNs. PDE10A contributes to the regulation of the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Both substitutions affect highly conserved amino acids located in the regulatory GAF-B domain, which, by binding to cAMP, stimulates the activity of the PDE10A catalytic domain. In silico modeling showed that the altered residues are located deep in the binding pocket, where they are likely to alter cAMP binding properties. In vitro functional studies showed that neither substitution affects the basal PDE10A activity, but they severely disrupt the stimulatory effect mediated by cAMP binding to the GAF-B domain. The identification of PDE10A mutations as a cause of chorea further motivates the study of cAMP signaling in MSNs and highlights the crucial role of striatal cAMP signaling in the regulation of basal ganglia circuitry. Pharmacological modulation of this pathway could offer promising etiologically targeted treatments for chorea and other hyperkinetic movement disorders. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. A Win-Win-Win Proposition -- Academia and Industry Working Together for Students

    Science.gov (United States)

    Cogswell, J.

    2011-12-01

    geoscience, to include having applied real problem solving via a robust field camp experience. In addition, we look for the maturity and ability to conduct independent research, to integrate broad suites of data, and to work as a team. We look for the ability to communicate results. We do not look for a focus on petroleum. We have many decades of experience in how to best develop that particular discipline quickly, to meet current and future business conditions. There are recurring themes that facilitate successful transition from Academia to a practicing industry geoscientist. These themes include giving students a good grounding in STEM, not just geology; one-on-one mentoring; sharing our passion for the science by sharing our research; and sharing the entire breadth of career opportunities. Similar best practices have been identified to encourage under-represented minority students and women to study STEM. Perhaps this is a suite of habits we should be practicing more broadly. This suite of habits takes extra time, extra effort, and extra money. But if geoscience mentors in Academia, Industry, and professional societies work together, we will be able to create a win for Academia, a win for Industry, and a win for students. (1) Gonzales and Keane, 2011, "Status of the Geoscience Workforce -- 2011," AGI, p. 123.

  3. Rapid eye movement sleep behaviour disorder and striatal dopamine depletion in patients with Parkinson's disease.

    Science.gov (United States)

    Chung, S J; Lee, Y; Lee, J J; Lee, P H; Sohn, Y H

    2017-10-01

    Rapid eye movement sleep behaviour disorder (RBD) is related to striatal dopamine depletion. This study was performed to confirm whether clinically probable RBD (cpRBD) in patients with Parkinson's disease (PD) is associated with a specific pattern of striatal dopamine depletion. A prospective survey was conducted using the RBD Screening Questionnaire (RBDSQ) in 122 patients with PD who had undergone dopamine transporter (DAT) positron emission tomography scan. Patients with cpRBD (RBDSQ ≥ 7) exhibited greater motor deficits, predominantly in the less-affected side and axial symptoms, and were prescribed higher levodopa-equivalent doses at follow-up than those without cpRBD (RBDSQ ≤ 4), despite their similar disease and treatment durations. Compared to patients without cpRBD, those with cpRBD showed lower DAT activities in the putamen, particularly in the less-affected side in all putaminal subregions, and a tendency to be lower in the ventral striatum. In addition, greater motor deficits in patients with cpRBD than in those without cpRBD remained significant after controlling for DAT binding in the putamen and other confounding variables. These results demonstrated that the presence of RBD in patients with PD is associated with different patterns of both motor deficit distribution and striatal DAT depletion, suggesting that the presence of RBD represents a distinct PD subtype with a malignant motor parkinsonism. © 2017 EAN.

  4. Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients

    Directory of Open Access Journals (Sweden)

    Marios Politis

    2017-01-01

    Full Text Available We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D2R availability in Parkinson's disease (PD patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [11C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [11C]raclopride non-displaceable binding potential were generated from the dynamic [11C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate D2R and a mean 3.5% increase in putaminal D2R availability compared to healthy controls. Lower caudate [11C]raclopride BPND correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced D2R availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced D2Rs availability in both caudate and putamen. No associations between striatal D2R availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen D2R availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal D2R availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.

  5. A direct ROI quantification method for inherent PVE correction: accuracy assessment in striatal SPECT measurements

    Energy Technology Data Exchange (ETDEWEB)

    Vanzi, Eleonora; De Cristofaro, Maria T.; Sotgia, Barbara; Mascalchi, Mario; Formiconi, Andreas R. [University of Florence, Clinical Pathophysiology, Florence (Italy); Ramat, Silvia [University of Florence, Neurological and Psychiatric Sciences, Florence (Italy)

    2007-09-15

    The clinical potential of striatal imaging with dopamine transporter (DAT) SPECT tracers is hampered by the limited capability to recover activity concentration ratios due to partial volume effects (PVE). We evaluated the accuracy of a least squares method that allows retrieval of activity in regions of interest directly from projections (LS-ROI). An Alderson striatal phantom was filled with striatal to background ratios of 6:1, 9:1 and 28:1; the striatal and background ROIs were drawn on a coregistered X-ray CT of the phantom. The activity ratios of these ROIs were derived both with the LS-ROI method and with conventional SPECT EM reconstruction (EM-SPECT). Moreover, the two methods were compared in seven patients with motor symptoms who were examined with N-3-fluoropropyl-2-{beta}-carboxymethoxy-3-{beta}-(4-iodophenyl) (FP-CIT) SPECT, calculating the binding potential (BP). In the phantom study, the activity ratios obtained with EM-SPECT were 3.5, 5.3 and 17.0, respectively, whereas the LS-ROI method resulted in ratios of 6.2, 9.0 and 27.3, respectively. With the LS-ROI method, the BP in the seven patients was approximately 60% higher than with EM-SPECT; a linear correlation between the LS-ROI and the EM estimates was found (r = 0.98, p = 0.03). The LS-ROI PVE correction capability is mainly due to the fact that the ill-conditioning of the LS-ROI approach is lower than that of the EM-SPECT one. The LS-ROI seems to be feasible and accurate in the examination of the dopaminergic system. This approach can be fruitful in monitoring of disease progression and in clinical trials of dopaminergic drugs. (orig.)

  6. Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks

    Directory of Open Access Journals (Sweden)

    Kjell eFuxe

    2012-06-01

    Full Text Available Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT and histamine striatal afferents, the cholinergic interneurons and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal

  7. Teaching Win-Win Better Prepares Students for Subsequent Experiences in Life.

    Science.gov (United States)

    Brainard, Alan J.

    The psychology of competition and winning, especially in relation to learning and motivation, is discussed. The Personalized System of Instruction (PSI) approach to coursework is proposed as a means of using the winning philosophy in education. Also suggested is the inclusion into coursework design of a form of rhetoric developed by Carl Rogers…

  8. The Winning Alternative: Solving the Dilemma of the Win/Lose Syndrome.

    Science.gov (United States)

    Moore, Dorothy L.

    1986-01-01

    Suggests alternatives in solving the dilemma of the win/lose syndrome for young children participating in sports, games, and other competitive educational activities. Rather than reinforcing the "negative" aspects of competition ("winning is all," lack of participation, elimination), teachers should provide environments that help children to…

  9. Long-term changes of striatal dopamine D-2 receptors in patients with Parkinson's disease : A study with positron emission tomography and [C-11]Raclopride

    NARCIS (Netherlands)

    Antonini, A; Schwarz, J; Oertel, WH; Pogarell, O; Leenders, KL

    We used [C-11]raclopride (RACLO) and positron emission tomography (PET) to study longitudinally striatal dopamine D-2 receptor binding in nine patients with Parkinson's disease (PD) at an early drug-naive stage and 3-5 years later, when motor fluctuations had appeared in seven of them. Patients were

  10. Video lottery: winning expectancies and arousal.

    Science.gov (United States)

    Ladouceur, Robert; Sévigny, Serge; Blaszczynski, Alexander; O'Connor, Kieron; Lavoie, Marc E

    2003-06-01

    This study investigates the effects of video lottery players' expectancies of winning on physiological and subjective arousal. Participants were assigned randomly to one of two experimental conditions: high and low winning expectancies. Participants played 100 video lottery games in a laboratory setting while physiological measures were recorded. Level of risk-taking was controlled. Participants were 34 occasional or regular video lottery players. They were assigned randomly into two groups of 17, with nine men and eight women in each group. The low-expectancy group played for fun, therefore expecting to win worthless credits, while the high-expectancy group played for real money. Players' experience, demographic variables and subjective arousal were assessed. Severity of problem gambling was measured with the South Oaks Gambling Screen. In order to measure arousal, the average heart rate was recorded across eight periods. Participants exposed to high as compared to low expectations experienced faster heart rate prior to and during the gambling session. According to self-reports, it is the expectancy of winning money that is exciting, not playing the game. Regardless of the level of risk-taking, expectancy of winning is a cognitive factor influencing levels of arousal. When playing for fun, gambling becomes significantly less stimulating than when playing for money.

  11. America's war on drugs: who's winning

    OpenAIRE

    Diaz, Mary Lu Anna.

    1995-01-01

    Recently, Congress, the literary community, and the public at large have come to reconsider the war on drugs. There are many opinions regarding alternatives to this pseudo war or new measures to be taken in the war effort, but the ongoing effort itself has escaped evaluation (to determine if the United States is winning this campaign). The intent of this thesis, then, is to explore the objectives of the war on drugs, and to determine if America is winning. This work concludes that the current...

  12. How to win friends and influence people

    CERN Document Server

    Carnegie, Dale

    2010-01-01

    For more than sixty years the rock-solid, time-tested advice in this book has carried thousands of now famous people up the ladder of success in their business and personal lives. With more than fifteen million copies sold, How to Win Friends and Influence People is one of the best known motivational books in history, with proven advice for achieving success in life. You’ll learn: three fundamental techniques in handling people; six ways to make people like you; twelve ways to win people to you way of thinking; nine ways to change people without arousing resentment; and much, much more!

  13. BMC Ecology image competition: the winning images

    Science.gov (United States)

    2013-01-01

    BMC Ecology announces the winning entries in its inaugural Ecology Image Competition, open to anyone affiliated with a research institute. The competition, which received more than 200 entries from international researchers at all career levels and a wide variety of scientific disciplines, was looking for striking visual interpretations of ecological processes. In this Editorial, our academic Section Editors and guest judge Dr Yan Wong explain what they found most appealing about their chosen winning entries, and highlight a few of the outstanding images that didn’t quite make it to the top prize. PMID:23517630

  14. SigWinR; the SigWin-detector updated and ported to R.

    Science.gov (United States)

    de Leeuw, Wim C; Rauwerda, Han; Inda, Márcia A; Bruning, Oskar; Breit, Timo M

    2009-10-06

    Our SigWin-detector discovers significantly enriched windows of (genomic) elements in any sequence of values (genes or other genomic elements in a DNA sequence) in a fast and reproducible way. However, since it is grid based, only (life) scientists with access to the grid can use this tool. Therefore and on request, we have developed the SigWinR package which makes the SigWin-detector available to a much wider audience. At the same time, we have introduced several improvements to its algorithm as well as its functionality, based on the feedback of SigWin-detector end users. To allow usage of the SigWin-detector on a desktop computer, we have rewritten it as a package for R: SigWinR. R is a free and widely used multi platform software environment for statistical computing and graphics. The package can be installed and used on all platforms for which R is available. The improvements involve: a visualization of the input-sequence values supporting the interpretation of Ridgeograms; a visualization allowing for an easy interpretation of enriched or depleted regions in the sequence using windows of pre-defined size; an option that allows the analysis of circular sequences, which results in rectangular Ridgeograms; an application to identify regions of co-altered gene expression (ROCAGEs) with a real-life biological use-case; adaptation of the algorithm to allow analysis of non-regularly sampled data using a constant window size in physical space without resampling the data. To achieve this, support for analysis of windows with an even number of elements was added. By porting the SigWin-detector as an R package, SigWinR, improving its algorithm and functionality combined with adequate performance, we have made SigWin-detector more useful as well as more easily accessible to scientists without a grid infrastructure.

  15. SigWinR; the SigWin-detector updated and ported to R

    Directory of Open Access Journals (Sweden)

    Breit Timo M

    2009-10-01

    Full Text Available Abstract Background Our SigWin-detector discovers significantly enriched windows of (genomic elements in any sequence of values (genes or other genomic elements in a DNA sequence in a fast and reproducible way. However, since it is grid based, only (life scientists with access to the grid can use this tool. Therefore and on request, we have developed the SigWinR package which makes the SigWin-detector available to a much wider audience. At the same time, we have introduced several improvements to its algorithm as well as its functionality, based on the feedback of SigWin-detector end users. Findings To allow usage of the SigWin-detector on a desktop computer, we have rewritten it as a package for R: SigWinR. R is a free and widely used multi platform software environment for statistical computing and graphics. The package can be installed and used on all platforms for which R is available. The improvements involve: a visualization of the input-sequence values supporting the interpretation of Ridgeograms; a visualization allowing for an easy interpretation of enriched or depleted regions in the sequence using windows of pre-defined size; an option that allows the analysis of circular sequences, which results in rectangular Ridgeograms; an application to identify regions of co-altered gene expression (ROCAGEs with a real-life biological use-case; adaptation of the algorithm to allow analysis of non-regularly sampled data using a constant window size in physical space without resampling the data. To achieve this, support for analysis of windows with an even number of elements was added. Conclusion By porting the SigWin-detector as an R package, SigWinR, improving its algorithm and functionality combined with adequate performance, we have made SigWin-detector more useful as well as more easily accessible to scientists without a grid infrastructure.

  16. Winning the sustainable development debate

    International Nuclear Information System (INIS)

    Ritch, John; Cornish, Emma

    2002-01-01

    on a vast scale Access to energy - and in particular, electricity - will be critical if the world is to achieve these human goals. Access to clean electricity - and on a vast scale - will be necessary if the world is to meet the twin challenges of human need and environmental security. Anti-nuclear forces, which have held sway in the Kyoto process thus far, argue that nuclear energy is a dying technology and assert passionately that it has no place in tomorrow's sustainable development agenda. These ideologically driven arguments ignore underlying realities both as to what is feasible and what is actually occurring. Today, nuclear power plants are operational in countries comprising 64% of the world's population, and new power reactors are in the planning or construction stage in countries representing no less than 50% of the world's population. Among the latter are the world's two largest developing countries, China and India, which alone represent 40% of humankind and about half the developing world. With active nuclear reactor construction under way as we speak, these leading nations have already made nuclear power a part of their sustainable development strategies for the 21st century. Winning the sustainable development debate - This presentation will share information materials about sustainable development. It will describe the work of the World Nuclear Association Sustainable Development Strategy Group, its preparations for the World Summit on Sustainable Development, and how participants to PIME can get involved. (author)

  17. Is there a relation between novelty seeking, striatal dopamine release and frontal cortical thickness?

    Directory of Open Access Journals (Sweden)

    Natalia Jaworska

    Full Text Available Novelty-seeking (NS and impulsive personality traits have been proposed to reflect an interplay between fronto-cortical and limbic systems, including the limbic striatum (LS. Although neuroimaging studies have provided some evidence for this, most are comprised of small samples and many report surprisingly large effects given the challenges of trying to relate a snapshot of brain function or structure to an entity as complex as personality. The current work tested a priori hypotheses about associations between striatal dopamine (DA release, cortical thickness (CT, and NS in a large sample of healthy adults.Fifty-two healthy adults (45M/7F; age: 23.8±4.93 underwent two positron emission tomography scans with [11C]raclopride (specific for striatal DA D2/3 receptors with or without amphetamine (0.3 mg/kg, p.o.. Structural magnetic resonance image scans were acquired, as were Tridimensional Personality Questionnaire data. Amphetamine-induced changes in [11C]raclopride binding potential values (ΔBPND were examined in the limbic, sensorimotor (SMS and associative (AST striatum. CT measures, adjusted for whole brain volume, were extracted from the dorsolateral sensorimotor and ventromedial/limbic cortices.BPND values were lower in the amphetamine vs. no-drug sessions, with the largest effect in the LS. When comparing low vs. high LS ΔBPND groups (median split, higher NS2 (impulsiveness scores were found in the high ΔBPND group. Partial correlations (age and gender as covariates yielded a negative relation between ASTS ΔBPND and sensorimotor CT; trends for inverse associations existed between ΔBPND values in other striatal regions and frontal CT. In other words, the greater the amphetamine-induced striatal DA response, the thinner the frontal cortex.These data expand upon previously reported associations between striatal DA release in the LS and both NS related impulsiveness and CT in the largest sample reported to date. The findings add to the

  18. An Application to WIN/ISIS Database on Local Network

    OpenAIRE

    Robert Lechien; Mohamed Salem Ghonem - Translator

    2005-01-01

    A Translated Article containing an application to how WIN/ISIS database work on local network. It starts with main definitions, and how to install WIN/ISIS on PC, and how to install it on the local network server.

  19. Assessment of striatal & postural deformities in patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2016-01-01

    Interpretation & conclusions: Our results showed that striatal and postural deformities were common and present in about half of the patients with PD. These deformities we more common in patients with advanced stage of PD.

  20. Prefrontal cortex and striatal activation by feedback in Parkinson's disease

    NARCIS (Netherlands)

    Keitz, Martijn; Koerts, Janneke; Kortekaas, Rudie; Renken, Remco; de Jong, Bauke M.; Leenders, Klaus L.

    2008-01-01

    Positive feedbacks reinforce goal-directed behavior and evoke pleasure. in Parkinson's disease (PD) the striatal dysfunction impairs motor performance, but also may lead to decreased positive feedback (reward) processing. This study investigates two types of positive feedback processing (monetary

  1. Striatal dysfunction in attention deficit and hyperkinetic disorder

    Energy Technology Data Exchange (ETDEWEB)

    Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

    1989-01-01

    We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD.

  2. Striatal dysfunction in attention deficit and hyperkinetic disorder

    International Nuclear Information System (INIS)

    Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

    1989-01-01

    We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD

  3. Defeating ISIS by Winning the War of Ideas

    Science.gov (United States)

    2017-03-17

    United States tell if it is winning the war of ideas? Robert Reilly, author of Assessing the War of Ideas during War, explains that the winning the war...AU/ACSC/2017 AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY DEFEATING ISIS BY WINNING THE WAR OF IDEAS by Lt Col Lyson Siame...Approved for public release: distribution unlimited. Defeating ISIS by Winning the War of Ideas 2 Disclaimer The views expressed in this academic

  4. The Feasibility of Using CT-Guided ROI for Semiquantifying Striatal Dopamine Transporter Availability in a Hybrid SPECT/CT System

    Directory of Open Access Journals (Sweden)

    Chien-Chin Hsu

    2014-01-01

    Full Text Available A hybrid SPECT/CT system provides accurate coregistration of functional and morphological images. CT-guided region of interest (ROI for semiquantifying striatal dopamine transporter (DAT availability may be a feasible method. We therefore assessed the intra- and interobserver reproducibility of manual SPECT and CT-guided ROI methods and compared their semiquantitative data with data from MRI-guided ROIs. We enrolled twenty-eight patients who underwent Tc-99m TRODAT-1 brain SPECT/CT and brain MRI. ROIs of the striatal, caudate, putamen, and occipital cortex were manually delineated on the SPECT, CT, and MRI. ROIs from CT and MRI were transferred to the coregistered SPECT for semiquantification. The striatal, caudate, and putamen nondisplaceable binding potential (BPND were calculated. Using CT-guided ROIs had higher intra- and interobserver concordance correlation coefficients, closer Bland-Altman biases to zero, and narrower limits of agreement than using manual SPECT ROIs. The correlation coefficients of striatal, caudate, and putamen BPND were good between manual SPECT and MRI-guided ROI methods and even better between CT-guided and MRI-guided ROI methods. Conclusively, CT-guided ROI delineation for semiquantifying striatal DAT availability in a hybrid SPECT/CT system is highly reproducible, and the semiquantitative data correlate well with data from MRI-guided ROIs.

  5. Striatal grafts in a rat model of Huntington's disease

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O

    1999-01-01

    Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...... eminences grown as free-floating roller-tube cultures can be successfully grafted in a rat Huntington model and that a clinical MR scanner offers a useful noninvasive tool for studying striatal graft development....

  6. Striatal direct and indirect pathways control decision-making behavior

    OpenAIRE

    Macpherson, Tom; Morita, Makiko; Hikida, Takatoshi

    2014-01-01

    Despite our ever-changing environment, animals are remarkably adept at selecting courses of action that are predictive of optimal outcomes. While requiring the contribution of a number of brain regions, a vast body of evidence implicates striatal mechanisms of associative learning and action selection to be critical to this ability. While numerous models of striatal-based decision-making have been developed, it is only recently that we have begun to understand the precise contributions of spe...

  7. Effects of isomers of apomorphines on dopamine receptors in striatal and limbic tissue of rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Kula, N.S.; Baldessarini, R.J.; Bromley, S.; Neumeyer, J.L.

    1985-09-16

    The optical isomers of apomorphine (APO) and N-propylnorapomorphine (NPA) were interacted with three biochemical indices of dopamine (Da) receptors in extrapyramidal and limbic preparations of rat brain tissues. There were consistent isomeric preferences for the R(-) configuration of both DA analogs in stimulation adenylate cyclase (D-1 sites) and in competing for high affinity binding of /sup 3/H-spiroperidol (D-2 sites) and of /sup 3/H-ADTN (DA agonist binding sites) in striatal tissue, with lesser isomeric differences in the limbic tissue. The S(+) apomorphines did not inhibit stimulation of adenylate cyclase by DA. The tendency for greater activity of higher apparent affinity of R(-) apomorphines in striatum may reflect the evidently greater abundance of receptor sites in that region. There were only small regional differences in interactions of the apomorphine isomers with all three receptor sites, except for a strong preference of (-)NPA for striatal D-2 sites. These results do not parallel our recent observations indicating potent and selective antidopaminergic actions of S(+) apomorphines in the rat limbic system. They suggest caution in assuming close parallels between current biochemical functional, especially behavioral, methods of evaluating dopamine receptors of mammalian brain.

  8. A win-win strategy for ecological restoration and biodiversity conservation in Southern China

    Science.gov (United States)

    Cao, Shixiong; Shang, Di; Yue, Hui; Ma, Hua

    2017-04-01

    Environmental degradation and poverty are linked, and must be tackled together. Doing so requires a win-win strategy that both restores the environment and ensures a sustainable livelihood for those who are affected by the restoration project. To understand the importance of combining ecological restoration and biodiversity conservation objectives with a consideration of the livelihoods of residents, we examined a successful project in ecologically fragile Changting County, Fujian Province, China. We attribute the project’s success to the development of a win-win strategy that sustainably improved resident livelihoods, in contrast with traditional strategies that focus exclusively on establishing forests and grassland. To develop this win-win strategy, we performed long-term monitoring (since 1984) under a program designed to permit ecological restoration and biodiversity conservation in the county. For our analysis, we chose a range of natural and socioeconomic indicators that could affect the ecological restoration; we then used a contribution model to identify the relative influence of each social, economic, or environmental factor on the dependent variables (vegetation cover, soil erosion, number of plant species). The results showed that by improving livelihoods and mitigating poverty in the long term, the project also reduced damage to the environment by local residents. Our calculations suggest that accounting for socioeconomic factors played a key role in the successful ecological conservation. This win-win path to escaping the poverty trap during ecological restoration provides an example that can be followed by restoration projects elsewhere in the world with suitable modifications to account for unique local conditions.

  9. Win-win strategies in directing low-carbon resilient development path

    International Nuclear Information System (INIS)

    Masui, Toshihiko; Kainuma, Mikiko

    2015-01-01

    This section explores big win-win strategies in directing low carbon resilient development path. There are lots of “leapfrog” development possibilities in developing countries, which go directly from a status of under-development through to efficient and environmentally benign lifestyle. To achieve low carbon resilient paths, not only technology development but also institutional and behavioral changes are required. Science-policy nexus is also discussed.

  10. Studies of the biogenic amine transporters. 1. Dopamine reuptake blockers inhibit [3H]mazindol binding to the dopamine transporter by a competitive mechanism: preliminary evidence for different binding domains.

    Science.gov (United States)

    Dersch, C M; Akunne, H C; Partilla, J S; Char, G U; de Costa, B R; Rice, K C; Carroll, F I; Rothman, R B

    1994-02-01

    The present study addressed the hypothesis that the DA transporter ligand, [3H]mazindol, labels multiple sites/states associated with the dopamine (DA) transporter in striatal membranes. Incubations with [3H]mazindol proceeded for 18-24 hr at 4 degrees C in 55.2 mM sodium phosphate buffer, pH 7.4, with a protease inhibitor cocktail. In order to obtain data suitable for quantitative curve fitting, it was necessary to repurify the [3H]mazindol by HPLC before a series of experiments. Under these conditions, we observed greater than 80% specific binding. The method of binding surface analysis was used to characterize the interaction of GBR12935, BTCP, mazindol, and CFT with binding site/sites labeled by [3H]mazindol. A one site model fit the data as well as the two site model: Bmax = 16911 fmol/mg protein, Kd of [3H]mazindol = 75 nM, Ki of GBR12935 = 8.1 nM, Ki of CFT = 50 nM and Ki of BTCP = 44 nM. The inhibitory mechanism (competitive or noncompetitive) of several drugs (GBR12935, CFT, BTCP, cocaine, cis-flupentixol, nomifensine, WIN35,065-2, bupropion, PCP, and benztropine) was determined. All drugs inhibited [3H]mazindol binding by a competitive mechanism. Although the ligand-selectivity of the [3H]mazindol binding site indicates that it is the uptake inhibitor recognition site of the classic DA transporter, the quantitative differences among the ligand-selectivities of different radioligands for the same site suggest that each radioligand labels different overlapping domains of the DA uptake inhibitor recognition site. It is likely that development of domain-selective drugs may further our understanding of the DA transporter.

  11. Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice

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    Miñarro José

    2010-03-01

    Full Text Available Abstract Background Numerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice. Methods In the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, reinstatement of the preference was induced by 0.5 or 0.1 mg/kg of WIN. Results A low dose of WIN 55212-2 (0.1 mg/kg increased the rewarding effects of low doses of MDMA (1.25 mg/kg, although a decrease in the preference induced by MDMA (5 and 2.5 mg/kg was observed when the dose of WIN 55212-2 was raised (0.5 mg/kg. The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose and did not block the effects of WIN. Animals treated with the highest WIN dose plus a non-neurotoxic dose of MDMA exhibited decreases of striatal DA and serotonin in the cortex. On the other hand, WIN 55212-2-induced CPP was reinstated by priming injections of MDMA, although WIN did not reinstate the MDMA-induced CPP. Conclusions These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA.

  12. Win-Win-Win: Reflections from a Work-Integrated Learning Project in a Non-Profit Organization

    Directory of Open Access Journals (Sweden)

    Dale C MacKrell

    2016-05-01

    Full Text Available This paper reports on the educational aspects of an information systems work-integrated learning (WIL capstone project for an organization which operates to alleviate homelessness in the Australian non-profit sector. The methodology adopted for the study is Action Design Research (ADR which draws on action research and design research as a means for framing a project's progress. Reflective insights by the project stakeholders, namely, students, academics, and the non-profit client, reveal a curriculum at work through internal features of the organization; personal features of the participants and features of the external environment. Preliminary findings suggest that students in a WIL project for a non-profit are highly engaged, especially when they become aware of the project’s social value. As well, the improvement of professional skills and emotional intelligence by students is more likely in real-life practice settings than in other less authentic WIL activities, equipping graduates for the workforce with both strong disciplinary and generic skills. Win-win-win synergies through project collaboration represent worthwhile outcomes to education, industry and research.

  13. Striatal dysfunction in X-linked dystonia-parkinsonism is associated with disease progression.

    Science.gov (United States)

    Brüggemann, N; Rosales, R L; Waugh, J L; Blood, A J; Domingo, A; Heldmann, M; Jamora, R D; Münchau, A; Münte, T F; Lee, L V; Buchmann, I; Klein, C

    2017-05-01

    X-linked dystonia-parkinsonism (XDP) is an inherited neurodegenerative adult-onset movement disorder associated with striatal atrophy. As the dopaminergic system has not yet been systemically studied in this basal ganglia model disease, it is unclear whether nigrostriatal dysfunction contributes to parkinsonism in XDP. Pre- and post-synaptic dopaminergic function was assessed in XDP. A total of 10 123 jod-benzamide (IBZM) single-photon emission computed tomography (SPECT) images were obtained for nine patients aged 42.3 ± 9.5 years (SD; range 30-52) and one asymptomatic mutation carrier (38 years), and four ioflupane (FP-CIT) SPECT images were obtained for four patients, aged 41.5 ± 11.6 years (range 30-52 years). Structural magnetic resonance imaging was also performed for all mutation carriers and 10 matched healthy controls. All patients were men who suffered from severe, disabling segmental or generalized dystonia and had varying degrees of parkinsonism. IBZM SPECT images were pathological in 8/9 symptomatic patients with distinct reduced post-synaptic tracer uptake in the caudate nucleus and putamen, and unremarkable in the asymptomatic mutation carrier. Longer disease duration was correlated with lower IBZM binding ratios. All subjects exhibited slightly reduced FP-CIT uptake values compared to controls for each analyzed region (-37% to -41%) which may be linked to basal ganglia volume loss. Visual inspection revealed physiological FP-CIT uptake in 1/4 patients. This nuclear imaging study provides evidence that the functional decline of post-synaptic dopaminergic neurotransmission is related to disease duration and ongoing neurodegeneration. Given the severe striatal cell loss which could be verified with post-synaptic nuclear imaging, both parkinsonism and dystonia in XDP are probably mainly due to striatal dysfunction. © 2017 EAN.

  14. TRPC1 Deletion Causes Striatal Neuronal Cell Apoptosis and Proteomic Alterations in Mice

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    Dian Wang

    2018-03-01

    Full Text Available Transient receptor potential channel 1 (TRPC1 is widely expressed throughout the nervous system, while its biological role remains unclear. In this study, we showed that TRPC1 deletion caused striatal neuronal loss and significantly increased TUNEL-positive and 8-hydroxy-2′-deoxyguanosine (8-OHdG staining in the striatum. Proteomic analysis by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE coupled with mass spectrometry (MS revealed a total of 51 differentially expressed proteins (26 increased and 25 decreased in the stratum of TRPC1 knockout (TRPC1−/− mice compared to that of wild type (WT mice. Bioinformatics analysis showed these dysregulated proteins included: oxidative stress-related proteins, synaptic proteins, endoplasmic reticulum (ER stress-related proteins and apoptosis-related proteins. STRING analysis showed these differential proteins have a well-established interaction network. Based on the proteomic data, we revealed by Western-blot analysis that TRPC1 deletion caused ER stress as evidenced by the dysregulation of GRP78 and PERK activation-related signaling pathway, and elevated oxidative stress as suggested by increased 8-OHdG staining, increased NADH dehydrogenase (ubiquinone flavoprotein 2 (NDUV2 and decreased protein deglycase (DJ-1, two oxidative stress-related proteins. In addition, we also demonstrated that TRPC1 deletion led to significantly increased apoptosis in striatum with concurrent decrease in both 14–3–3Z and dynamin-1 (D2 dopamine (DA receptor binding, two apoptosis-related proteins. Taken together, we concluded that TRPC1 deletion might cause striatal neuronal apoptosis by disturbing multiple biological processes (i.e., ER stress, oxidative stress and apoptosis-related signaling. These data suggest that TRPC1 may be a key player in the regulation of striatal cellular survival and death.

  15. Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia.

    Science.gov (United States)

    Simonyan, Kristina; Berman, Brian D; Herscovitch, Peter; Hallett, Mark

    2013-09-11

    Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia-thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [(11)C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ΔBP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ΔBP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ΔBP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ΔBP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder.

  16. Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity

    Directory of Open Access Journals (Sweden)

    Mathieu Baudonnat

    2017-05-01

    Full Text Available Different parallel neural circuits interact and may even compete to process and store information: whereas stimulus–response (S–R learning critically depends on the dorsal striatum (DS, spatial memory relies on the hippocampus (HPC. Strikingly, despite its potential importance for our understanding of addictive behaviors, the impact of drug rewards on memory systems dynamics has not been extensively studied. Here, we assessed long-term effects of drug- vs food reinforcement on the subsequent use of S–R vs spatial learning strategies and their neural substrates. Mice were trained in a Y-maze cue-guided task, during which either food or morphine injections into the ventral tegmental area (VTA were used as rewards. Although drug- and food-reinforced mice learned the Y-maze task equally well, drug-reinforced mice exhibited a preferential use of an S–R learning strategy when tested in a water-maze competition task designed to dissociate cue-based and spatial learning. This cognitive bias was associated with a persistent increase in the phosphorylated form of cAMP response element-binding protein phosphorylation (pCREB within the DS, and a decrease of pCREB expression in the HPC. Pharmacological inhibition of striatal PKA pathway in drug-rewarded mice limited the morphine-induced increase in levels of pCREB in DS and restored a balanced use of spatial vs cue-based learning. Our findings suggest that drug (opiate reward biases the engagement of separate memory systems toward a predominant use of the cue-dependent system via an increase in learning-related striatal pCREB activity. Persistent functional imbalance between striatal and hippocampal activity could contribute to the persistence of addictive behaviors, or counteract the efficiency of pharmacological or psychotherapeutic treatments.

  17. Chemical anatomy of striatal interneurons in normal individuals and in patients with Huntington's disease.

    Science.gov (United States)

    Cicchetti, F; Prensa, L; Wu, Y; Parent, A

    2000-11-01

    This paper reviews the major anatomical and chemical features of the various types of interneurons in the human striatum, as detected by immunostaining procedures applied to postmortem tissue from normal individuals and patients with Huntington's disease (HD). The human striatum harbors a highly pleomorphic population of aspiny interneurons that stain for either a calcium-binding protein (calretinin, parvalbumin or calbindin D-28k), choline acetyltransferase (ChAT) or NADPH-diaphorase, or various combinations thereof. Neurons that express calretinin (CR), including multitudinous medium and a smaller number of large neurons, are by far the most abundant interneurons in the human striatum. The medium CR+ neurons do not colocalize with any of the known chemical markers of striatal neurons, except perhaps GABA, and are selectively spared in HD. Most large CR+ interneurons display ChAT immunoreactivity and also express substance P receptors. The medium and large CR+ neurons are enriched with glutamate receptor subunit GluR2 and GluR4, respectively. This difference in AMPA GluR subunit expression may account for the relative resistance of medium CR+ neurons to glutamate-mediated excitotoxicity that may be involved in HD. The various striatal chemical markers display a highly heterogeneous distribution pattern in human. In addition to the classic striosomes/matrix compartmentalization, the striosomal compartment itself is composed of a core and a peripheral region, each subdivided by distinct subsets of striatal interneurons. A proper knowledge of all these features that appear unique to humans should greatly help our understanding of the organization of the human striatum in both health and disease states.

  18. Dysfunction and dysconnection in cortical-striatal networks during sustained attention: Genetic risk for schizophrenia or bipolar disorder and its impact on brain network function

    Directory of Open Access Journals (Sweden)

    Vaibhav A. Diwadkar

    2014-05-01

    Full Text Available Abnormalities in the brain’s attention network may represent early identifiable neurobiological impairments in individuals at increased risk for schizophrenia or bipolar disorder. Here we provide evidence of dysfunctional regional and network function in adolescents at higher genetic risk for schizophrenia or bipolar disorder (henceforth HGR. During fMRI, participants engaged in a sustained attention task with variable demands. The task alternated between attention (120 s, visual control (passive viewing; 120 s and rest (20 s epochs. Low and high demand attention conditions were created using the rapid presentation of 2- or 3-digit numbers. Subjects were required to detect repeated presentation of numbers. We demonstrate that the recruitment of cortical and striatal regions are disordered in HGR: Relative to typical controls (TC, HGR showed lower recruitment of the dorsal prefrontal cortex, but higher recruitment of the superior parietal cortex. This imbalance was more dramatic in the basal ganglia. There, a group by task demand interaction was observed, such that increased attention demand led to increased engagement in TC, but disengagement in HGR. These activation studies were complemented by network analyses using Dynamic Causal Modeling. Competing model architectures were assessed across a network of cortical-striatal regions, distinguished at a second level using random effects Bayesian model selection. In the winning architecture, HGR were characterized by significant reductions in coupling across both frontal-striatal and frontal-parietal pathways. The effective connectivity analyses indicate emergent network dysconnection, consistent with findings in patients with schizophrenia. Emergent patterns of regional dysfunction and disconnection in cortical-striatal pathways may provide functional biological signatures in the adolescent risk state for psychiatric illness.

  19. Winning public and political support for nuclear

    International Nuclear Information System (INIS)

    McFadden, D.J.

    2006-01-01

    The nuclear industry is entering an historic battle for the hearts and minds of Canadians as government decides on nuclear new build. Recent polls indicate that public support is rising for nuclear power. However, the support could be eroded by negative events or intense lobbying by anti-nuclear groups. The nuclear industry must deal with concerns raised about nuclear power, such as cost, safety, reliability and waste. The nuclear industry should build upon the positive movement in public support. The industry must go to Canadians with a credible message which responds effectively to public concerns. It must be remembered that winning public support will be essential to winning and maintaining political support. (author)

  20. From chaos to control: winning the war.

    Science.gov (United States)

    Wojciak, P J

    1994-08-01

    This article illustrates how a small manufacturing facility in the Midwest undertook the process of an MRP II implementation and ultimately gained class A status at a true make-or-break time in its history. The control that was gained throughout the entire process has helped create a winning environment and will continue to strengthen our position as we move toward world-class excellence.

  1. How winning changes motivation in multiphase competitions.

    Science.gov (United States)

    Huang, Szu-Chi; Etkin, Jordan; Jin, Liyin

    2017-06-01

    What drives motivation in multiphase competitions? Adopting a dynamic approach, this research examines how temporary standing-being ahead of (vs. behind) one's opponent-in a multiphase competition shapes subsequent motivation. Six competitions conducted in the lab and in the field demonstrate that the impact of being ahead on contestants' motivation depends on when (i.e., in which phase of the competition) contestants learn they are in the lead. In the early phase, contestants are concerned about whether they can win; being ahead increases motivation by making winning seem more attainable. In the later phase, however, contestants are instead driven by how much additional effort they believe they need to invest; being ahead decreases motivation by reducing contestants' estimate of the remaining effort needed to win. Temporary standing thus has divergent effects on motivation in multiphase competitions, driven by a shift in contestants' main concern from the early to the later phase and thus the meaning they derive from being ahead of their opponent. By leveraging insights gained from approaching individuals' self-regulation as a dynamic process, this research advances understanding of how motivation evolves in a unique interdependent self-regulatory context. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  2. Does human presynaptic striatal dopamine function predict social conformity?

    Science.gov (United States)

    Stokes, Paul R A; Benecke, Aaf; Puraite, Julita; Bloomfield, Michael A P; Shotbolt, Paul; Reeves, Suzanne J; Lingford-Hughes, Anne R; Howes, Oliver; Egerton, Alice

    2014-03-01

    Socially desirable responding (SDR) is a personality trait which reflects either a tendency to present oneself in an overly positive manner to others, consistent with social conformity (impression management (IM)), or the tendency to view one's own behaviour in an overly positive light (self-deceptive enhancement (SDE)). Neurochemical imaging studies report an inverse relationship between SDR and dorsal striatal dopamine D₂/₃ receptor availability. This may reflect an association between SDR and D₂/₃ receptor expression, synaptic dopamine levels or a combination of the two. In this study, we used a [¹⁸F]-DOPA positron emission tomography (PET) image database to investigate whether SDR is associated with presynaptic dopamine function. Striatal [¹⁸F]-DOPA uptake, (k(i)(cer), min⁻¹), was determined in two independent healthy participant cohorts (n=27 and 19), by Patlak analysis using a cerebellar reference region. SDR was assessed using the revised Eysenck Personality Questionnaire (EPQ-R) Lie scale, and IM and SDE were measured using the Paulhus Deception Scales. No significant associations were detected between Lie, SDE or IM scores and striatal [¹⁸F]-DOPA k(i)(cer). These results indicate that presynaptic striatal dopamine function is not associated with social conformity and suggests that social conformity may be associated with striatal D₂/₃ receptor expression rather than with synaptic dopamine levels.

  3. Temporal changes of striatal dopamine release during and after a video game with a monetary reward: a PET study with [11C]raclopride continuous infusion

    International Nuclear Information System (INIS)

    Kim, S. E.; Cho, S. S.; Choe, Y. S.; Lee, S. Y.; Kang, E.; Kim, B. T.

    2002-01-01

    In an attempt to understand the neurochemical changes associated with rewarded motor learning in human brain, we investigated the temporal changes of striatal dopamine (DA) release during and after a goal-directed psychomotor task (a video game) with a monetary incentive using [ 11 C]raclopride PET. Seven healthy, right-handed, nonsmokers were studied with PET for 120 min (50 min resting followed by 40 min video game and another 30 min resting) while receiving a bolus plus constant infusion of the DA D2 receptor radioligand [ 11 C]raclopride. During the video game (from 50 to 90 min postinjection), subjects played Tetris, which involved learning of joystick movement to fit falling jigsaw blocks, and periodically rewarded with unpredictable amount monetary incentives for improved performance. Striatal V3', calculated as striatal-cerebellar/cerebellar activity ratio, was measured under equilibrium condition, at baseline and during and after the video game. Striatal V3' was significantly reduced during the video game compared with baseline levels, indicating increased DA release in this region (caudate, -15±6%; putamen, -30±10%). During the 30 min after the game ended, striatal [ 11 C]raclopride binding was gradually increased and the V3' approached baseline levels. There was a significant correlation between the reduction in striatal V3' and the task performance during the video game. These results demonstrate DA release in the human striatum during a psychomotor task with a monetary reward and to our knowledge for the first time a gradual DA restoration to baseline levels following the offset of stimulation. They also illustrate that acute fluctuations of synaptic DA can be measured in vivo using [ 11 C]raclopride PET

  4. Temporal changes of striatal dopamine release during and after a video game with a monetary reward: a PET study with [11C] raclopride continuous infusion

    International Nuclear Information System (INIS)

    Sang Eun Kim; Yearn Seong Choe; Eunjoo Kang; Dong Soo Lee; June-Key Chung; Myung-Chul Lee; Sang Soo Cho

    2004-01-01

    Purpose: In an attempt to understand the neurochemical changes associated with rewarded motor learning in human brain, we investigated the temporal changes of striatal dopamine (DA) release during and after a goal-directed psychomotor task (a video game) with a monetary incentive using [ 11 C] raclopride PET. Methods: Seven healthy, right-handed, nonsmokers were studied with PET for 120 min (50 min resting followed by 40 min video game and another 30 min resting) while receiving a bolus plus constant infusion of the DA D2 receptor radioligand [ 11 C] raclopride. During the video game (from 50 to 90 min postinjection), subjects played Tetris, which involved learning of joystick movement to fit falling jigsaw blocks, and periodically rewarded with unpredictable amount monetary incentives for improved performance. Striatal V 3 ', calculated as striatal-cerebellar/cerebellar activity ratio, was measured under equilibrium condition, at baseline and during and after the video game. Results: Striatal V 3 ' was significantly reduced during the video game compared with baseline levels, indicating increased DA release in this region (caudate, -15±6%; putamen, -30±10%). During the 30 min after the game ended, striatal [ 11 C] raclopride binding was gradually increased and the V 3 ' approached baseline levels. There was a significant correlation between the reduction in striatal V 3 ' and the task performance during the video game. Conclusions: These results demonstrate DA release in the human striatum during a psychomotor task with a monetary reward and to our knowledge for the first time a gradual DA restoration to baseline levels following the offset of stimulation. They also illustrate that acute fluctuations of synaptic DA can be measured in vivo using [ 11 C] raclopride PET. (authors)

  5. Temporal changes of striatal dopamine release during and after a video game with a monetary reward: a PET study with [{sup 11}C]raclopride continuous infusion

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S. E. [Sungkyunkwon University School of Medicine, Suwon (Korea, Republic of); Cho, S. S.; Choe, Y. S.; Lee, S. Y.; Kang, E.; Kim, B. T. [Seoul National University hospital, Seoul (Korea, Republic of)

    2002-07-01

    In an attempt to understand the neurochemical changes associated with rewarded motor learning in human brain, we investigated the temporal changes of striatal dopamine (DA) release during and after a goal-directed psychomotor task (a video game) with a monetary incentive using [{sup 11}C]raclopride PET. Seven healthy, right-handed, nonsmokers were studied with PET for 120 min (50 min resting followed by 40 min video game and another 30 min resting) while receiving a bolus plus constant infusion of the DA D2 receptor radioligand [{sup 11}C]raclopride. During the video game (from 50 to 90 min postinjection), subjects played Tetris, which involved learning of joystick movement to fit falling jigsaw blocks, and periodically rewarded with unpredictable amount monetary incentives for improved performance. Striatal V3', calculated as striatal-cerebellar/cerebellar activity ratio, was measured under equilibrium condition, at baseline and during and after the video game. Striatal V3' was significantly reduced during the video game compared with baseline levels, indicating increased DA release in this region (caudate, -15{+-}6%; putamen, -30{+-}10%). During the 30 min after the game ended, striatal [{sup 11}C]raclopride binding was gradually increased and the V3' approached baseline levels. There was a significant correlation between the reduction in striatal V3' and the task performance during the video game. These results demonstrate DA release in the human striatum during a psychomotor task with a monetary reward and to our knowledge for the first time a gradual DA restoration to baseline levels following the offset of stimulation. They also illustrate that acute fluctuations of synaptic DA can be measured in vivo using [{sup 11}C]raclopride PET.

  6. WIN Global. 1977/98 Activities at a First Glance

    International Nuclear Information System (INIS)

    Rising, A.; Lopez CArbonell, M.T.; Perez-Griffo, M.L.

    1998-01-01

    WIN is a worldwide association of women working professionally in the fields of nuclear energy and applications of radiation. The goal of WIN is to contribute to objectively inform the public on nuclear and radiation. WIN's principal objective is to emphasis and support the role that women can and do have in addressing the general public's concerns about nuclear energy and the application of radiation and nuclear technology. WIN is doing this through educational programmes, information exchange and arranging study visits. Members of WIN all have one thing in common: they want the general public to have a better understanding of nuclear and radiation matters. Membership status as ao April 21, 1998 was 605 members from 39 countries. During the year 7 new countries have joined to WIN ant two national WIN groups have been formed. Purpose of this paper is to present, to the Spanish Nuclear Society members, the WIN Global activities all over the world for the period 1997/98. The information included herein comes from different sources and WIN members and is, of course, a quick look over those activities. Win Spain activities for the period will be presented in a different paper of this Annual Meeting. (Author) 2 refs

  7. Decreased striatal D2 receptor density associated with severe behavioral abnormality in Alzheimer's disease

    International Nuclear Information System (INIS)

    Tanaka, Yasuhiro; Meguro, Kenichi; Yamaguchi, Satoshi

    2003-01-01

    Since patients manifesting behavioral and psychological symptoms of dementia (BPSD) are a burden for their families and caregivers, the underlying neurobiological mechanism of this condition should be clarified. Using positron emission tomography (PET), we previously reported that wandering behavior in dementia was associated with a disturbed dopaminergic neuron system. We herein investigated the relationship between the severity of BPSD and the striatal D 2 receptor density in Alzheimer's disease (AD). Ten patients with probable AD as per the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the AD and Related Disorders Association (ADRDA) criteria and five normal subjects were examined with PET. The tracer used was [ 11 C]raclopride (D 2 antagonist). The uptake of [ 11 C]raclopride was calculated as the estimation of binding potential (BP) of the striatum to the cerebellum. The AD patients were institutionalized in multiple nursing homes, and their BPSD were evaluated by the Behavioral Pathology in AD Frequency Weighted Severity Scale (BEHAVE-AD-FW) scale (Reisberg). There was a significant inverse Spearman's correlation between BEHAVE-AD-FW score and the BP, especially between the score of the behavioral domain and the BP values. The BP was found to be lower in severer BPSD patients. Patients with AD who manifest severe BPSD may have some dysfunction of striatal dopamine metabolism compared with those without BPSD. (author)

  8. Regulation of GABA and benzodiazepine receptors following neurotoxin-induced striatal and medial forebrain bundle lesions

    International Nuclear Information System (INIS)

    Pan, H.S.I.

    1985-01-01

    GABA, a major inhibitory transmitter, is used by many projection neurons of the striatum. To investigate the role of GABA in striatal function, the GABA receptor complex was studied after lesions of the striatum or the nigrostriatal neurons. Quantitative receptor autoradiography using thaw-mounted tissue slices was developed for the study of GABA and benzodiazepine (BDZ) receptors. With the technique established, binding to GABA and BDZ receptors after unilateral striatal kainate lesions was examined. Subsequently, changes in GABA and BDZ receptors were studied following the destruction of dopaminergic nigrostriatal cells by unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. In summary, quantitative receptor autoradiography allowed the detection of GABA and BDZ receptor changes in multiple small areas in each lesioned brain. This technique made it feasible to carry out kinetic saturation, and competition studies using less than 1 mg of tissue. The data suggest that dopamine is functionally inhibitory on striatopallidal neurons but is functionally excitatory on striatoentopeduncular and striatonigral cells which in turn inhibit the thalamus. This quantitative autoradiographic technique can be generalized to study other transmitter receptors and can be combined with 2-deoxyglucose uptake studies

  9. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain—striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand......, dopamine release coded uncertainty, we would find an inversely U-shaped function. The data supported an inverse U-shaped relation between striatal dopamine release and IGT performance if the pathological gambling group, but not in the healthy control group. These results are consistent with the hypothesis...

  10. Re-emergence of striatal cholinergic interneurons in movement disorders.

    Science.gov (United States)

    Pisani, Antonio; Bernardi, Giorgio; Ding, Jun; Surmeier, D James

    2007-10-01

    Twenty years ago, striatal cholinergic neurons were central figures in models of basal ganglia function. But since then, they have receded in importance. Recent studies are likely to lead to their re-emergence in our thinking. Cholinergic interneurons have been implicated as key players in the induction of synaptic plasticity and motor learning, as well as in motor dysfunction. In Parkinson's disease and dystonia, diminished striatal dopaminergic signalling leads to increased release of acetylcholine by interneurons, distorting network function and inducing structural changes that undoubtedly contribute to the symptoms. By contrast, in Huntington's disease and progressive supranuclear palsy, there is a fall in striatal cholinergic markers. This review gives an overview of these recent experimental and clinical studies, placing them within the context of the pathogenesis of movement disorders.

  11. Impairment of striatal mitochondrial function by acute paraquat poisoning.

    Science.gov (United States)

    Czerniczyniec, Analía; Lanza, E M; Karadayian, A G; Bustamante, J; Lores-Arnaiz, S

    2015-10-01

    Mitochondria are essential for survival. Their primary function is to support aerobic respiration and to provide energy for intracellular metabolic pathways. Paraquat is a redox cycling agent capable of generating reactive oxygen species. The aim of the present study was to evaluate changes in cortical and striatal mitochondrial function in an experimental model of acute paraquat toxicity and to compare if the brain areas and the molecular mechanisms involved were similar to those observed after chronic exposure. Sprague-Dawley rats received paraquat (25 mg/Kg i.p.) or saline and were sacrificed after 24 h. Paraquat treatment decreased complex I and IV activity by 37 and 21 % respectively in striatal mitochondria. Paraquat inhibited striatal state 4 and state 3 KCN-sensitive respiration by 80 % and 62 % respectively, indicating a direct effect on respiratory chain. An increase of 2.2 fold in state 4 and 2.3 fold in state 3 in KCN-insensitive respiration was observed in striatal mitochondria from paraquat animals, suggesting that paraquat redox cycling also consumed oxygen. Paraquat treatment increased hydrogen peroxide production (150 %), TBARS production (42 %) and cardiolipin oxidation/depletion (12 %) in striatal mitochondria. Also, changes in mitochondrial polarization was induced after paraquat treatment. However, no changes were observed in any of these parameters in cortical mitochondria from paraquat treated-animals. These results suggest that paraquat treatment induced a clear striatal mitochondrial dysfunction due to both paraquat redox cycling reactions and impairment of the mitochondrial electron transport, causing oxidative damage. As a consequence, mitochondrial dysfunction could probably lead to alterations in cellular bioenergetics.

  12. Amphetamine and Dopamine-Induced Immediate Early Gene Expression in Striatal Neurons Depends on Postsynaptic NMDA Receptors and Calcium

    Science.gov (United States)

    Konradi, Christine; Leveque, Jean-Christophe; Hyman, Steven E.

    2014-01-01

    Amphetamine and cocaine induce the expression of both immediate early genes (IEGs) and neuropeptide genes in rat striatum. Despite the demonstrated dependence of these effects on D1 dopamine receptors, which activate the cyclic AMP pathway, there are several reports that amphetamine and cocaine-induced IEG expression can be inhibited in striatum in vivo by NMDA receptor antagonists. We find that in vivo, the NMDA receptor antagonist MK-801 inhibits amphetamine induction of c-fos acutely and also prevents downregulation of IEG expression with chronic amphetamine administration. Such observations raise the question of whether dopamine/glutamate interactions occur at the level of corticostriatal and mesostriatal circuitry or within striatal neurons. Therefore, we studied dissociated striatal cultures in which midbrain and cortical presynaptic inputs are removed. In these cultures, we find that dopamine- or forskolin-mediated IEG induction requires Ca2+ entry via NMDA receptors but not via L-type Ca2+ channels. Moreover, blockade of NMDA receptors diminishes the ability of dopamine to induce phosphorylation of the cyclic AMP responsive element binding protein CREB. Although these results do not rule out a role for circuit-level dopamine/glutamate interactions, they demonstrate a requirement at the cellular level for interactions between the cyclic AMP and NMDA receptor pathways in dopamine-regulated gene expression in striatal neurons. PMID:8753884

  13. Proteostasis in striatal cells and selective neurodegeneration in Huntington's disease.

    Science.gov (United States)

    Margulis, Julia; Finkbeiner, Steven

    2014-01-01

    Selective neuronal loss is a hallmark of neurodegenerative diseases, including Huntington's disease (HD). Although mutant huntingtin, the protein responsible for HD, is expressed ubiquitously, a subpopulation of neurons in the striatum is the first to succumb. In this review, we examine evidence that protein quality control pathways, including the ubiquitin proteasome system, autophagy, and chaperones, are significantly altered in striatal neurons. These alterations may increase the susceptibility of striatal neurons to mutant huntingtin-mediated toxicity. This novel view of HD pathogenesis has profound therapeutic implications: protein homeostasis pathways in the striatum may be valuable targets for treating HD and other misfolded protein disorders.

  14. Differential effects of delayed aging on phenotype and striatal pathology in a murine model of Huntington disease.

    Science.gov (United States)

    Tallaksen-Greene, Sara J; Sadagurski, Marianna; Zeng, Li; Mauch, Roseanne; Perkins, Matthew; Banduseela, Varuna C; Lieberman, Andrew P; Miller, Richard A; Paulson, Henry L; Albin, Roger L

    2014-11-19

    The common neurodegenerative syndromes exhibit age-related incidence, and many Mendelian neurodegenerative diseases exhibit age-related penetrance. Mutations slowing aging retard age related pathologies. To assess whether delayed aging retards the effects of a mutant allele causing a Huntington's disease (HD)-like syndrome, we generated compound mutant mice, placing a dominant HD knock-in polyglutamine allele onto the slow-aging Snell dwarf genotype. The Snell genotype did not affect mutant huntingtin protein expression. Bigenic and control mice were evaluated prospectively from 10 to 100 weeks of age. Adult HD knock-in allele mice lost weight progressively with weight loss blunted significantly in male bigenic HD knock-in/Snell dwarf mice. Impaired balance beam performance developed significantly more slowly in bigenic HD knock-in/Snell dwarf mice. Striatal dopamine receptor expression was diminished significantly and similarly in all HD-like mice, regardless of the Snell genotype. Striatal neuronal intranuclear inclusion burden was similar between HD knock-in mice with and without the Snell genotype, whereas nigral neuropil aggregates were diminished in bigenic HD knock-in/Snell dwarf mice. Compared with control mice, Snell dwarf mice exhibited differences in regional benzodiazepine and cannabinoid receptor binding site expression. These results indicate that delaying aging delayed behavioral decline with little effect on the development of striatal pathology in this model of HD but may have altered synaptic pathology. These results indicate that mutations prolonging lifespan in mice delay onset of significant phenotypic features of this model and also demonstrate dissociation between striatal pathology and a commonly used behavioral measure of disease burden in HD models. Copyright © 2014 the authors 0270-6474/14/3415658-11$15.00/0.

  15. In vivo evaluation of striatal dopamine reuptake sites using 11C-nomifensine and positron emission tomography

    International Nuclear Information System (INIS)

    Aquilonius, S.-M.; Bergstroem, K.; Eckernaes, S.-Aa.; Leenders, K.L.; Hartvig, P.; Lundquist, H.; Antoni, G.; Gee, A.; Rimland, A.; Uhlin, J.; Langstroem, B.

    1987-01-01

    In vitro nomifensine demonstrates high affinity and specificity for dopamine reuptake sites in the brain. In the present study 11 C-nomifensine was administered i.v. in trace amounts (10-50 μg) to ketamine anaesthetized Rhesus monkeys (6-10 kg b.w.) and the timecourse of radioactivity within different brain regions was measured by positron emission tomography (PET). Six base-line experiments lasting for 60-80 min were performed. The procedure was repeated after pretreatment with nomifensine (2-6 mg/kg i.v.), another reuptake inhibitor, mazindol (0.3 mg/kg i.v.), desipramine (0.5 mg/kg i.v.) or spiperone (0.3 mg/kg i.v.) before the administration of a second 11 C-nomifensine dose. The highest radioactivity uptake was found in the dopamine innervated striatum and the lowest in a region containing the cerebellum, known to be almost devoid of dopaminergic neurons. The difference between striatal and cerebellar uptake of 11 C-nomifensine derived radioactivity was markedly reduced after nomifensine and mazindol but not after desipramine and spiperone. These results indicate that in vivo the striatal uptake of 11 C-nomifensine, as measured with PET, involves specific binding with the dopamine reuptake sites. In the first human applications of 11 C-nomifensine and PET in a healthy volunteer, the regional uptake of radioactivity was similar to that in base-line experiments with Rhesus monkeys. In the healthy subject the striatal/cerebellar ratio was 1.6, 50 min after the injection of 11 C-nomifensine. In a hemi-parkinsonian patient this ratio was 1.1 contralaterally and 1.3 ipsilaterally to the affected side. 11 C-nomifensine and PET seems to be an auspicious method to measure the striatal dopaminergic nerve terminals of man in vivo. (author)

  16. In vivo evaluation of striatal dopamine reuptake sites using /sup 11/C-nomifensine and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Aquilonius, S.-M.; Bergstroem, K.; Eckernaes, S.-Aa.; Leenders, K.L.; Hartvig, P.; Lundquist, H.; Antoni, G.; Gee, A.; Rimland, A.; Uhlin, J.

    1987-01-01

    In vitro nomifensine demonstrates high affinity and specificity for dopamine reuptake sites in the brain. In the present study /sup 11/C-nomifensine was administered i.v. in trace amounts (10-50 ..mu..g) to ketamine anaesthetized Rhesus monkeys (6-10 kg b.w.) and the timecourse of radioactivity within different brain regions was measured by positron emission tomography (PET). Six base-line experiments lasting for 60-80 min were performed. The procedure was repeated after pretreatment with nomifensine (2-6 mg/kg i.v.), another reuptake inhibitor, mazindol (0.3 mg/kg i.v.), desipramine (0.5 mg/kg i.v.) or spiperone (0.3 mg/kg i.v.) before the administration of a second /sup 11/C-nomifensine dose. The highest radioactivity uptake was found in the dopamine innervated striatum and the lowest in a region containing the cerebellum, known to be almost devoid of dopaminergic neurons. The difference between striatal and cerebellar uptake of /sup 11/C-nomifensine derived radioactivity was markedly reduced after nomifensine and mazindol but not after desipramine and spiperone. These results indicate that in vivo the striatal uptake of /sup 11/C-nomifensine, as measured with PET, involves specific binding with the dopamine reuptake sites. In the first human applications of /sup 11/C-nomifensine and PET in a healthy volunteer, the regional uptake of radioactivity was similar to that in base-line experiments with Rhesus monkeys. In the healthy subject the striatal/cerebellar ratio was 1.6, 50 min after the injection of /sup 11/C-nomifensine. In a hemi-parkinsonian patient this ratio was 1.1 contralaterally and 1.3 ipsilaterally to the affected side. /sup 11/C-nomifensine and PET seems to be an auspicious method to measure the striatal dopaminergic nerve terminals of man in vivo.

  17. Infiltrating to Win: The Conduct of Border Denial Operations

    Science.gov (United States)

    2016-04-04

    must believe 14 Robert A. Pape, Bombing to Win : Air Power and Coercion in War (Ithaca, NY: Cornell University Press, 1996), 4. 15 Ibid., 7. 16 Ibid...Vietnam. Chicago, IL: University of Chicago Press, 2002. Pape, Robert A. Bombing to Win : Air Power and Coercion in War. Ithaca, NY: Cornell University...Infiltrating to Win : The Conduct of Border Denial Operations A Monograph by MAJ Craig A. Broyles United

  18. A winning strategy for 3 x n Cylindrical Hex

    DEFF Research Database (Denmark)

    Huneke, S. C.; Hayward, R.; Toft, Bjarne

    2014-01-01

    For Cylindrical Hex on a board with circumference 3, we give a winning strategy for the end-to-end player. This is the first known winning strategy for odd circumference at least 3, answering a question of David Gale. (C) 2014 Elsevier B.V. All rights reserved.......For Cylindrical Hex on a board with circumference 3, we give a winning strategy for the end-to-end player. This is the first known winning strategy for odd circumference at least 3, answering a question of David Gale. (C) 2014 Elsevier B.V. All rights reserved....

  19. SigWinR; the SigWin-detector updated and ported to R

    NARCIS (Netherlands)

    de Leeuw, W.C.; Rauwerda, H.; Inda, M.A.; Bruning, O.; Breit, T.M.

    2009-01-01

    Background Our SigWin-detector discovers significantly enriched windows of (genomic) elements in any sequence of values (genes or other genomic elements in a DNA sequence) in a fast and reproducible way. However, since it is grid based, only (life) scientists with access to the grid can use this

  20. Dysregulation of striatal projection neurons in Parkinson's disease.

    Science.gov (United States)

    Beck, Goichi; Singh, Arun; Papa, Stella M

    2018-03-01

    The loss of nigrostriatal dopamine (DA) is the primary cause of motor dysfunction in Parkinson's disease (PD), but the underlying striatal mechanisms remain unclear. In spite of abundant literature portraying structural, biochemical and plasticity changes of striatal projection neurons (SPNs), in the past there has been a data vacuum from the natural human disease and its close model in non-human primates. Recently, single-cell recordings in advanced parkinsonian primates have generated new insights into the altered function of SPNs. Currently, there are also human data that provide direct evidence of profoundly dysregulated SPN activity in PD. Here, we review primate recordings that are impacting our understanding of the striatal dysfunction after DA loss, particularly through the analysis of physiologic correlates of parkinsonian motor behaviors. In contrast to recordings in rodents, data obtained in primates and patients demonstrate similar major abnormalities of the spontaneous SPN firing in the alert parkinsonian state. Furthermore, these studies also show altered SPN responses to DA replacement in the advanced parkinsonian state. Clearly, there is yet much to learn about the striatal discharges in PD, but studies using primate models are contributing unique information to advance our understanding of pathophysiologic mechanisms.

  1. Striatal volume predicts level of video game skill acquisition.

    Science.gov (United States)

    Erickson, Kirk I; Boot, Walter R; Basak, Chandramallika; Neider, Mark B; Prakash, Ruchika S; Voss, Michelle W; Graybiel, Ann M; Simons, Daniel J; Fabiani, Monica; Gratton, Gabriele; Kramer, Arthur F

    2010-11-01

    Video game skills transfer to other tasks, but individual differences in performance and in learning and transfer rates make it difficult to identify the source of transfer benefits. We asked whether variability in initial acquisition and of improvement in performance on a demanding video game, the Space Fortress game, could be predicted by variations in the pretraining volume of either of 2 key brain regions implicated in learning and memory: the striatum, implicated in procedural learning and cognitive flexibility, and the hippocampus, implicated in declarative memory. We found that hippocampal volumes did not predict learning improvement but that striatal volumes did. Moreover, for the striatum, the volumes of the dorsal striatum predicted improvement in performance but the volumes of the ventral striatum did not. Both ventral and dorsal striatal volumes predicted early acquisition rates. Furthermore, this early-stage correlation between striatal volumes and learning held regardless of the cognitive flexibility demands of the game versions, whereas the predictive power of the dorsal striatal volumes held selectively for performance improvements in a game version emphasizing cognitive flexibility. These findings suggest a neuroanatomical basis for the superiority of training strategies that promote cognitive flexibility and transfer to untrained tasks.

  2. Dorsal striatal dopamine, food preference and health perception in humans

    NARCIS (Netherlands)

    Wallace, D.L.; Aarts, E.; Dang, L.C.; Greer, S.M.; Jagust, W.J.; D'Esposito, M.

    2014-01-01

    To date, few studies have explored the neurochemical mechanisms supporting individual differences in food preference in humans. Here we investigate how dorsal striatal dopamine, as measured by the positron emission tomography (PET) tracer [(18)F]fluorometatyrosine (FMT), correlates with food-related

  3. Cue-induced striatal dopamine release in Parkinson's disease-associated impulsive-compulsive behaviours.

    Science.gov (United States)

    O'Sullivan, Sean S; Wu, Kit; Politis, Marios; Lawrence, Andrew D; Evans, Andrew H; Bose, Subrata K; Djamshidian, Atbin; Lees, Andrew J; Piccini, Paola

    2011-04-01

    Impulsive-compulsive behaviours are a significant source of morbidity for patients with Parkinson's disease receiving dopaminergic therapy. The development of these behaviours may reflect sensitization of the neural response to non-drug rewards, similar to that proposed for sensitization to drug rewards in addiction. Here, by using (11)C-raclopride positron emission tomography imaging, we investigated the effects of reward-related cues and L-dopa challenge in patients with Parkinson's disease with and without impulsive-compulsive behaviours on striatal levels of synaptic dopamine. Eighteen patients (11 with and seven without impulsive-compulsive behaviours) underwent three (11)C-raclopride positron emission tomography scans. The impulsive-compulsive behaviours included hypersexuality, binge eating, punding, compulsive use of dopamine replacement therapy, compulsive buying and pathological gambling, with eight patients exhibiting more than one impulsive-compulsive behaviour. There were no significant differences in baseline dopamine D2 receptor availability between the Parkinson's disease groups. No differences were found when comparing the percentage change of raclopride binding potential between the two Parkinson's disease groups following L-dopa challenge with neutral cues. The group with Parkinson's disease with impulsive-compulsive behaviours had a greater reduction of ventral striatum (11)C-raclopride binding potential following reward-related cue exposure, relative to neutral cue exposure, following L-dopa challenge (16.3% compared with 5.8% in Parkinson's disease controls, P = 0.016). The heightened response of striatal reward circuitry to heterogeneous reward-related visual cues among a group of patients with different impulsive-compulsive behaviours is consistent with a global sensitization to appetitive behaviours with dopaminergic therapy in vulnerable individuals. Our findings are relevant for the broader debate on the relation between impulsive

  4. Interactions between alpha-latrotoxin and trivalent cations in rat striatal synaptosomal preparations

    Energy Technology Data Exchange (ETDEWEB)

    Scheer, H.W.

    1989-05-01

    The interactions between alpha-latrotoxin (alpha-LTx), a neurosecretagogue purified from the venom of the black widow spider, and the trivalent cations Al3+, Y3+, La3+, Gd3+, and Yb3+ were investigated in rat striatal synaptosomal preparations. All trivalent cations tested were inhibitors of alpha-LTx-induced (/sup 3/H)dopamine ((/sup 3/H)DA) release (order of potency: Yb3+ greater than Gd3+ approximately Y3+ greater than La3+ greater than Al3+). Only with Al3+ could inhibition of (/sup 3/H)DA release be attributed to a block of /sup 125/I-alpha-LTx specific binding to synaptosomal preparations. The inhibitory effect of trivalent ions was reversible provided synaptosomes were washed with buffer containing EDTA. Trivalent ions also inhibited alpha-LTx-induced (/sup 3/H)DA release at times when alpha-LTx-stimulated release was already evident. alpha-LTx-induced synaptosomal membrane depolarization was blocked by La3+, but not affected by Gd3+, Y3+, and Yb3+. alpha-LTx-stimulated uptake of /sup 45/Ca/sup 2 +/ was inhibited by all trivalent cations tested. These results demonstrate that there exist at least three means by which trivalent cations can inhibit alpha-LTx action in rat striatal synaptosomal preparations: (1) inhibition of alpha-LTx binding (Al3+); (2) inhibition of alpha-LTx-induced depolarization (La3+); and (3) inhibition of alpha-LTx-induced /sup 45/Ca/sup 2 +/ uptake (Gd3+, Y3+, Yb3+, La3+).

  5. Rat striatal muscarinic receptors coupled to the inhibition of adenylyl cyclase activity: potent block by the selective m4 ligand muscarinic toxin 3 (MT3).

    Science.gov (United States)

    Olianas, M C; Adem, A; Karlsson, E; Onali, P

    1996-05-01

    1. In rat striatal membranes, muscarinic toxin 3 (MT3), a selective ligand of the cloned m4 receptor subtype, antagonized the acetylcholine (ACh) inhibition of forskolin- and dopamine D1 receptor-stimulated adenylyl cyclase activities with pA2 values of 8.09 and 8.15, respectively. 2. In radioligand binding experiments, MT3 increased the Kd but did not change the Bmax value of [3H]-N-methylscopolamine (3H]-NMS) binding to rat striatal muscarinic receptors. The toxin displaced the major portion of the [3H]-NMS binding sites with a Ki of 8.0 nM. 3. In rat myocardium, MT3 antagonized the ACh inhibition of adenylyl cyclase with a Ki value of 860 nM. 4. In rat cerebral cortical membranes prelabelled with [3H]-myo-inositol, MT3 counteracted the methacholine stimulation of [3H]-inositol phosphates formation with a Ki value of 113 nM. 5. The present study shows that MT3 is a potent antagonist of the striatal muscarinic receptors coupled to inhibition of adenylyl cyclase activity. This finding provides strong evidence for the classification of these receptors as pharmacologically equivalent to the m4 gene product (M4). On the other hand, the weaker potencies of MT3 in antagonizing the muscarinic responses in cerebral cortex and in the heart are consistent with the reported lower affinities of the toxin for the cloned m1 and m2 receptor subtypes, respectively.

  6. CERN exhibition wins yet another design prize

    CERN Multimedia

    Joannah Caborn Wengler

    2012-01-01

    The “Universe of Particles” exhibition in CERN’s Globe wins the silver design prize from the German direct business communications association FAMAB.   Not only do tens of thousands of people visit the “Universe of Particles” exhibition each year, but juries for design prizes are crossing its threshold more and more frequently too. In 2011 alone it claimed 8 awards, including winning outright the 2011 Annual Multimedia award, the iF Communication Design for Corporate Architecture award and the Modern Decoration Media award (the Bulletin already reported on some of these in July 2011). The FAMAB award is the latest to join the prestigious list. The jury of FAMAB’s “ADAM 2011” award was particularly impressed by the hands-on nature of the exhibition, which encourages visitors to get interested in science. They also appreciated the way that the space in the Globe is not just a container for the exhibits, but itself ...

  7. The Relationship between Teachers' and Principals' Decision-Making Power: Is It a Win-Win Situation or a Zero-Sum Game?

    Science.gov (United States)

    Shen, Jianping; Xia, Jiangang

    2012-01-01

    Is the power relationship between public school teachers and principals a win-win situation or a zero-sum game? By applying hierarchical linear modeling to the 1999-2000 nationally representative Schools and Staffing Survey data, we found that both the win-win and zero-sum-game theories had empirical evidence. The decision-making areas…

  8. No effect of blue on winning contests in judo

    NARCIS (Netherlands)

    Dijkstra, Peter D.; Preenen, Paul T. Y.

    2008-01-01

    A study by Rowe et al. reported a winning bias for judo athletes wearing a blue outfit relative to those wearing a white one during the 2004 Olympics. It was suggested that blue is associated with a higher likelihood of winning through differential effects of colour on opponent visibility and/or an

  9. Does Blue Uniform Color Enhance Winning Probability in Judo Contests?

    NARCIS (Netherlands)

    Dijkstra, P.D.; Preenen, P.T.Y.; Essen, H. van

    2018-01-01

    The color of an athlete's uniform may have an effect on psychological functioning and consequently bias the chances of winning contests in sport competition. Several studies reported a winning bias for judo athletes wearing a blue outfit relative to those wearing a white outfit. However, we argue

  10. Setting Win Limits: An Alternative Approach to "Responsible Gambling"?

    Science.gov (United States)

    Walker, Douglas M; Litvin, Stephen W; Sobel, Russell S; St-Pierre, Renée A

    2015-09-01

    Social scientists, governments, and the casino industry have all emphasized the need for casino patrons to "gamble responsibly." Strategies for responsible gambling include self-imposed time limits and loss limits on gambling. Such strategies help prevent people from losing more than they can afford and may help prevent excessive gambling behavior. Yet, loss limits also make it more likely that casino patrons leave when they are losing. Oddly, the literature makes no mention of "win limits" as a potential approach to responsible gambling. A win limit would be similar to a loss limit, except the gambler would leave the casino upon reaching a pre-set level of winnings. We anticipate that a self-imposed win limit will reduce the gambler's average loss and, by default, also reduce the casino's profit. We test the effect of a self-imposed win limit by running slot machine simulations in which the treatment group of players has self-imposed and self-enforced win and loss limits, while the control group has a self-imposed loss limit or no limit. We find that the results conform to our expectations: the win limit results in improved player performance and reduced casino profits. Additional research is needed, however, to determine whether win limits could be a useful component of a responsible gambling strategy.

  11. An Application to WIN/ISIS Database on Local Network

    Directory of Open Access Journals (Sweden)

    Robert Lechien

    2005-07-01

    Full Text Available A Translated Article containing an application to how WIN/ISIS database work on local network. It starts with main definitions, and how to install WIN/ISIS on PC, and how to install it on the local network server.

  12. Future aircraft cabins and design thinking: optimisation vs. win-win scenarios

    Directory of Open Access Journals (Sweden)

    A. Hall

    2013-06-01

    Full Text Available With projections indicating an increase in mobility over the next few decades and annual flight departures expected to rise to over 16 billion by 2050, there is a demand for the aviation industry and associated stakeholders to consider new forms of aircraft and technology. Customer requirements are recognized as a key driver in business. The airline is the principal customer for the aircraft manufacture. The passenger is, in turn, the airline's principal customer but they are just one of several stakeholders that include aviation authorities, airport operators, air-traffic control and security agencies. The passenger experience is a key differentiator used by airlines to attract and retain custom and the fuselage that defines the cabin envelope for the in-flight passenger experience and cabin design therefore receives significant attention for new aircraft, service updates and refurbishments. Decision making in design is crucial to arriving at viable and worthwhile cabin formats. Too little innovation will result in an aircraft manufacturer and airlines using its products falling behind its competitors. Too much may result in an over-extension with, for example, use of immature technologies that do not have the necessary reliability for a safety critical industry or sufficient value to justify the development effort. The multiple requirements associated with cabin design, can be viewed as an area for optimisation, accepting trade-offs between the various parameters. Good design, however, is often defined as developing a concept that resolves the contradictions and takes the solution towards a win-win scenario. Indeed our understanding and practice of design allows for behaviors that enhance design thinking through divergence and convergence, the use of abductive reasoning, experimentation and systems thinking. This paper explores and defines the challenges of designing the aircraft cabin of the future that will deliver on the multiple

  13. The Bamberg Trucking Game: A Paradigm for Assessing the Detection of Win-Win Solutions in a Potential Conflict Scenario.

    Science.gov (United States)

    Nalis, Dario; Schütz, Astrid; Pastukhov, Alexander

    2018-01-01

    In win-win solutions, all parties benefit more from the solution than they would if they each pursued their own individual goals. Such solutions are beneficial at individual and collective levels and thus represent optimal solutions. Win-win solutions are desirable but often difficult to find. To allow the study of individual differences and situational factors that help or hinder the detection of win-win solutions, we created a paradigm that fills a gap in the repertoire of psychological instruments used to assess collaboration, cooperation, negotiation, and prosocial behavior. The new paradigm differs from previous ones in two aspects: (a) In existing paradigms that focus on social motivation, possible strategies are evident, whereas we focused here on the question of whether people can detect the solution and thus disentangle ability from motivation, (b) Paradigms that focus on cooperation typically entail a risk associated with the partner's defection, whereas cooperation in our paradigm is not associated with risk. We adjusted the Trucking Game-a method for assessing bargaining-to include a situation in which two parties can help each other achieve their respective goals and thus benefit over and above the pursuit of individual goals or compromising. We tested scenario-based and interaction-based versions with samples of 154 and 112 participants, respectively. Almost one third of the participants or dyads found the win-win solution. General mental abilities were not related to detecting the win-win solution in either version. The paradigm provides a way to extend research on cooperation and conflict and can thus be useful for research and training.

  14. Striatal Pre- and Postsynaptic Profile of Adenosine A2A Receptor Antagonists

    Science.gov (United States)

    Quiroz, César; Beaumont, Vahri; Goldberg, Steven R.; Lluís, Carme; Cortés, Antoni; Franco, Rafael; Casadó, Vicent; Canela, Enric I.; Ferré, Sergi

    2011-01-01

    Striatal adenosine A2A receptors (A2ARs) are highly expressed in medium spiny neurons (MSNs) of the indirect efferent pathway, where they heteromerize with dopamine D2 receptors (D2Rs). A2ARs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A1 receptors (A1Rs). It has been hypothesized that postsynaptic A2AR antagonists should be useful in Parkinson's disease, while presynaptic A2AR antagonists could be beneficial in dyskinetic disorders, such as Huntington's disease, obsessive-compulsive disorders and drug addiction. The aim or this work was to determine whether selective A2AR antagonists may be subdivided according to a preferential pre- versus postsynaptic mechanism of action. The potency at blocking the motor output and striatal glutamate release induced by cortical electrical stimulation and the potency at inducing locomotor activation were used as in vivo measures of pre- and postsynaptic activities, respectively. SCH-442416 and KW-6002 showed a significant preferential pre- and postsynaptic profile, respectively, while the other tested compounds (MSX-2, SCH-420814, ZM-241385 and SCH-58261) showed no clear preference. Radioligand-binding experiments were performed in cells expressing A2AR-D2R and A1R-A2AR heteromers to determine possible differences in the affinity of these compounds for different A2AR heteromers. Heteromerization played a key role in the presynaptic profile of SCH-442416, since it bound with much less affinity to A2AR when co-expressed with D2R than with A1R. KW-6002 showed the best relative affinity for A2AR co-expressed with D2R than co-expressed with A1R, which can at least partially explain the postsynaptic profile of this compound. Also, the in vitro pharmacological profile of MSX-2, SCH-420814, ZM-241385 and SCH-58261 was is in accordance with their mixed pre- and postsynaptic profile. On the basis of their preferential

  15. Striatal pre- and postsynaptic profile of adenosine A(2A receptor antagonists.

    Directory of Open Access Journals (Sweden)

    Marco Orru

    2011-01-01

    Full Text Available Striatal adenosine A(2A receptors (A(2ARs are highly expressed in medium spiny neurons (MSNs of the indirect efferent pathway, where they heteromerize with dopamine D(2 receptors (D(2Rs. A(2ARs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A(1 receptors (A(1Rs. It has been hypothesized that postsynaptic A(2AR antagonists should be useful in Parkinson's disease, while presynaptic A(2AR antagonists could be beneficial in dyskinetic disorders, such as Huntington's disease, obsessive-compulsive disorders and drug addiction. The aim or this work was to determine whether selective A(2AR antagonists may be subdivided according to a preferential pre- versus postsynaptic mechanism of action. The potency at blocking the motor output and striatal glutamate release induced by cortical electrical stimulation and the potency at inducing locomotor activation were used as in vivo measures of pre- and postsynaptic activities, respectively. SCH-442416 and KW-6002 showed a significant preferential pre- and postsynaptic profile, respectively, while the other tested compounds (MSX-2, SCH-420814, ZM-241385 and SCH-58261 showed no clear preference. Radioligand-binding experiments were performed in cells expressing A(2AR-D(2R and A(1R-A(2AR heteromers to determine possible differences in the affinity of these compounds for different A(2AR heteromers. Heteromerization played a key role in the presynaptic profile of SCH-442416, since it bound with much less affinity to A(2AR when co-expressed with D(2R than with A(1R. KW-6002 showed the best relative affinity for A(2AR co-expressed with D(2R than co-expressed with A(1R, which can at least partially explain the postsynaptic profile of this compound. Also, the in vitro pharmacological profile of MSX-2, SCH-420814, ZM-241385 and SCH-58261 was is in accordance with their mixed pre- and postsynaptic profile

  16. Striatal Vulnerability in Huntington’s Disease: Neuroprotection Versus Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Ryoma Morigaki

    2017-06-01

    Full Text Available Huntington’s disease (HD is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ in the huntingtin (Htt protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium spiny neurons and parvalbumin-expressing interneurons accompanied by neurodegeneration of the striosome and matrix compartments, leading to progressive impairment of reasoning, walking and speaking abilities. The precise cause of striatal pathology in HD is still unknown; however, accumulating clinical and experimental evidence suggests multiple plausible pathophysiological mechanisms underlying striatal neurodegeneration in HD. Here, we review and discuss the characteristic neurodegenerative patterns observed in the striatum of HD patients and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity and neuroprotection.

  17. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain—striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [11C]raclopride to measure...... dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

  18. Endocannabinoid-dopamine interactions in striatal synaptic plasticity

    Directory of Open Access Journals (Sweden)

    Brian Neil Mathur

    2012-04-01

    Full Text Available The nigrostriatal dopaminergic system is implicated in action control and learning. A large body of work has focused on the contribution of this system to modulation of the corticostriatal synapse, the predominant synapse type in the striatum. Signaling through the D2 dopamine receptor is necessary for endocannabinoid-mediated depression of corticostriatal glutamate release. Here we review the known details of this mechanism and discuss newly discovered signaling pathways interacting with this system that ultimately exert dynamic control of cortical input to the striatum and striatal output. This topic is timely with respect to Parkinson’s disease given recent data indicating changes in the striatal endocannabinoid system in patients with this disorder.

  19. The Cognitive Architecture of Spatial Navigation: Hippocampal and Striatal Contributions.

    Science.gov (United States)

    Chersi, Fabian; Burgess, Neil

    2015-10-07

    Spatial navigation can serve as a model system in cognitive neuroscience, in which specific neural representations, learning rules, and control strategies can be inferred from the vast experimental literature that exists across many species, including humans. Here, we review this literature, focusing on the contributions of hippocampal and striatal systems, and attempt to outline a minimal cognitive architecture that is consistent with the experimental literature and that synthesizes previous related computational modeling. The resulting architecture includes striatal reinforcement learning based on egocentric representations of sensory states and actions, incidental Hebbian association of sensory information with allocentric state representations in the hippocampus, and arbitration of the outputs of both systems based on confidence/uncertainty in medial prefrontal cortex. We discuss the relationship between this architecture and learning in model-free and model-based systems, episodic memory, imagery, and planning, including some open questions and directions for further experiments. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Centrality of striatal cholinergic transmission in basal ganglia function

    Directory of Open Access Journals (Sweden)

    Paola eBonsi

    2011-02-01

    Full Text Available Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction.Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson’s disease and dystonia.Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders.

  1. Motor tics evoked by striatal disinhibition in the rat

    Science.gov (United States)

    Bronfeld, Maya; Yael, Dorin; Belelovsky, Katya; Bar-Gad, Izhar

    2013-01-01

    Motor tics are sudden, brief, repetitive movements that constitute the main symptom of Tourette syndrome (TS). Multiple lines of evidence suggest the involvement of the cortico-basal ganglia system, and in particular the basal ganglia input structure—the striatum in tic formation. The striatum receives somatotopically organized cortical projections and contains an internal GABAergic network of interneurons and projection neurons' collaterals. Disruption of local striatal GABAergic connectivity has been associated with TS and was found to induce abnormal movements in model animals. We have previously described the behavioral and neurophysiological characteristics of motor tics induced in monkeys by local striatal microinjections of the GABAA antagonist bicuculline. In the current study we explored the abnormal movements induced by a similar manipulation in freely moving rats. We targeted microinjections to different parts of the dorsal striatum, and examined the effects of this manipulation on the induced tic properties, such as latency, duration, and somatic localization. Tics induced by striatal disinhibition in monkeys and rats shared multiple properties: tics began within several minutes after microinjection, were expressed solely in the contralateral side, and waxed and waned around a mean inter-tic interval of 1–4 s. A clear somatotopic organization was observed only in rats, where injections to the anterior or posterior striatum led to tics in the forelimb or hindlimb areas, respectively. These results suggest that striatal disinhibition in the rat may be used to model motor tics such as observed in TS. Establishing this reliable and accessible animal model could facilitate the study of the neural mechanisms underlying motor tics, and the testing of potential therapies for tic disorders. PMID:24065893

  2. Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Rosa M Villalba

    2011-08-01

    Full Text Available Striatal dopamine denervation is the pathological hallmark of Parkinson’s disease (PD. Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastructural features of the neuronal synaptic elements at the remaining corticostriatal and thalamostriatal glutamatergic axo-spinous synapses undergo complex ultrastructural remodeling consistent with increased synaptic activity (Villalba et al., 2011. The concept of tripartite synapses (TS was introduced a decade ago, according to which astrocytes process and exchange information with neuronal synaptic elements at glutamatergic synapses (Araque et al., 1999a. Although there has been compelling evidence that astrocytes are integral functional elements of tripartite glutamatergic synaptic complexes in the cerebral cortex and hippocampus, their exact functional role, degree of plasticity and preponderance in other CNS regions remain poorly understood. In this review, we discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We also present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia-neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD

  3. Motor tics evoked by striatal disinhibition in the rat

    Directory of Open Access Journals (Sweden)

    Maya eBronfeld

    2013-09-01

    Full Text Available Motor tics are sudden, brief, repetitive movements that constitute the main symptom of Tourette syndrome (TS. Multiple lines of evidence suggest the involvement of the cortico-basal ganglia system, and in particular the basal ganglia input structure – the striatum in tic formation. The striatum receives somatotopically organized cortical projections and contains an internal GABAergic network of interneurons and projection neurons collaterals. Disruption of local striatal GABAergic connectivity has been associated with TS and was found to induce abnormal movements in model animals. We have previously described the behavioral and neurophysiological characteristics of motor tics induced in monkeys by local striatal microinjections of the GABAA antagonist bicuculline. In the current study we explored the abnormal movements induced by a similar manipulation in freely moving rats. We targeted microinjections to different parts of the dorsal striatum, and examined the effects of this manipulation on the induced tic properties, such as latency, duration and somatic localization. Tics induced by striatal disinhibition in monkeys and rats shared multiple properties: tics began within several minutes after microinjection, were expressed solely in the contralateral side, and waxed and waned around a mean inter-tic interval of 1-4 s. A clear somatotopic organization was observed only in rats, where injections to the anterior or posterior striatum led to tics in the forelimb or hindlimb areas, respectively. These results suggest that striatal disinhibition in the rat may be used to model motor tics such as observed in TS. Establishing this reliable and accessible animal model could facilitate the study of the neural mechanisms underlying motor tics, and the testing of potential therapies for tic disorders.

  4. In vivo neurochemical characterization of clothianidin induced striatal dopamine release.

    Science.gov (United States)

    Faro, L R F; Oliveira, I M; Durán, R; Alfonso, M

    2012-12-16

    Clothianidin (CLO) is a neonicotinoid insecticide with selective action on nicotinic acetylcholine receptors. The aim of this study was to determine the neurochemical basis for CLO-induced striatal dopamine release using the microdialysis technique in freely moving and conscious rats. Intrastriatal administration of CLO (3.5mM), produced an increase in both spontaneous (2462 ± 627% with respect to basal values) and KCl-evoked (4672 ± 706% with respect to basal values) dopamine release. This effect was attenuated in Ca(2+)-free medium, and was prevented in reserpine pre-treated animals or in presence of tetrodotoxin (TTX). To investigate the involvement of dopamine transporter (DAT), the effect of CLO was observed in presence of nomifensine. The coadministration of CLO and nomifensine produced an additive effect on striatal dopamine release. The results suggest that the effect of CLO on striatal dopamine release is predominantly mediated by an exocytotic mechanism, Ca(2+), vesicular and TTX-dependent and not by a mechanism mediated by dopamine transporter. Published by Elsevier Ireland Ltd.

  5. Neuroinflammation alters voltage-dependent conductance in striatal astrocytes

    Science.gov (United States)

    Karpuk, Nikolay; Burkovetskaya, Maria

    2012-01-01

    Neuroinflammation has the capacity to alter normal central nervous system (CNS) homeostasis and function. The objective of the present study was to examine the effects of an inflammatory milieu on the electrophysiological properties of striatal astrocyte subpopulations with a mouse bacterial brain abscess model. Whole cell patch-clamp recordings were performed in striatal glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP)+ astrocytes neighboring abscesses at postinfection days 3 or 7 in adult mice. Cell input conductance (Gi) measurements spanning a membrane potential (Vm) surrounding resting membrane potential (RMP) revealed two prevalent astrocyte subsets. A1 and A2 astrocytes were identified by negative and positive Gi increments vs. Vm, respectively. A1 and A2 astrocytes displayed significantly different RMP, Gi, and cell membrane capacitance that were influenced by both time after bacterial exposure and astrocyte proximity to the inflammatory site. Specifically, the percentage of A1 astrocytes was decreased immediately surrounding the inflammatory lesion, whereas A2 cells were increased. These changes were particularly evident at postinfection day 7, revealing increased cell numbers with an outward current component. Furthermore, RMP was inversely modified in A1 and A2 astrocytes during neuroinflammation, and resting Gi was increased from 21 to 30 nS in the latter. In contrast, gap junction communication was significantly decreased in all astrocyte populations associated with inflamed tissues. Collectively, these findings demonstrate the heterogeneity of striatal astrocyte populations, which experience distinct electrophysiological modifications in response to CNS inflammation. PMID:22457466

  6. Transient and steady-state selection in the striatal microcircuit

    Directory of Open Access Journals (Sweden)

    Adam eTomkins

    2014-01-01

    Full Text Available Although the basal ganglia have been widely studied and implicated in signal processing and action selection, little information is known about the active role the striatal microcircuit plays in action selection in the basal ganglia-thalamo-cortical loops. To address this knowledge gap we use a large scale three dimensional spiking model of the striatum, combined with a rate coded model of the basal ganglia-thalamo-cortical loop, to asses the computational role the striatum plays in action selection. We identify a robust transient phenomena generated by the striatal microcircuit, which temporarily enhances the difference between two competing cortical inputs. We show that this transient is sufficient to modulate decision making in the basal ganglia-thalamo-cortical circuit. We also find that the transient selection originates from a novel adaptation effect in single striatal projection neurons, which is amenable to experimental testing. Finally, we compared transient selection with models implementing classical steady-state selection. We challenged both forms of model to account for recent reports of paradoxically enhanced response selection in Huntington's Disease patients. We found that steady-state selection was uniformly impaired under all simulated Huntington's conditions, but transient selection was enhanced given a sufficient Huntington's-like increase in NMDA receptor sensitivity. Thus our models provide an intriguing hypothesis for the mechanisms underlying the paradoxical cognitive improvements in manifest Huntington's patients.

  7. Fractal analysis of striatal dopamine re-uptake sites

    International Nuclear Information System (INIS)

    Kuikka, J.T.; Bergstroem, K.A.; Tiihonen, J.; Raesaenen, P.; Karhu, J.

    1997-01-01

    Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane ([ 123 I]β-CIT). The mean fractal dimension was 1.15±0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19±0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions. (orig.). With 5 figs., 1 tab

  8. Quantum Chinos game: winning strategies through quantum fluctuations

    International Nuclear Information System (INIS)

    Guinea, F; Martin-Delgado, M A

    2003-01-01

    We apply several quantization schemes to simple versions of the Chinos game. Classically, for two players with one coin each, there is a symmetric stable strategy that allows each player to win half of the times on average. A partial quantization of the game (semiclassical) allows us to find a winning strategy for the second player, but it is unstable w.r.t. the classical strategy. However, in a fully quantum version of the game we find a winning strategy for the first player that is optimal: the symmetric classical situation is broken at the quantum level. (letter to the editor)

  9. [3H]Dopamine accumulation and release from striatal slices in young, mature and senescent rats

    International Nuclear Information System (INIS)

    Thompson, J.M.

    1981-01-01

    Examinations of [ 3 H]dopamine ([ 3 H]DA) release following KCl or amphetamine administration in striatal slices from young (7 month), mature (12 month) and senescent (24 month) Wistar rats showed no age-related changes. Further, the amount of [ 3 H]DA accumulated in the striatal slices showed no changes with age. Thus, previously reported age-related deficits in motor behavior (i.e. rotational) are not produced by changes in striatal DA accumulation or release. (Auth.)

  10. Customer Satisfaction Perceptions of Dislocated Workers Served by WIN Job Centers in the Mississippi Corridor Consortium

    Science.gov (United States)

    Washburn, Dava Michelle

    2009-01-01

    The purpose of this study was to determine the perceptions of satisfaction of dislocated workers served by WIN Job Centers in the Mississippi Corridor Consortium. Four WIN Job Centers participated in this study: Northeast Mississippi Community College WIN Job Center in Corinth, Northwest Mississippi Community College WIN Job Center in Oxford,…

  11. Leaders in high temperature superconductivity commercialization win superconductor industry award

    CERN Multimedia

    2007-01-01

    CERN's Large Hadron Collider curretn leads project head Amalia Ballarino named superconductor industry person of the year 2006. Former high temperature superconductivity program manager at the US Department of energy James Daley wins lifetime achievement award. (1,5 page)

  12. Adenosine A2A receptors and A2A receptor heteromers as key players in striatal function

    Directory of Open Access Journals (Sweden)

    Sergi eFerre

    2011-06-01

    Full Text Available A very significant density of adenosine adenosine A2A receptors (A2ARs is present in the striatum, where they are preferentially localized postsynaptically in striatopallidal medium spiny neurons (MSNs. In this localization A2ARs establish reciprocal antagonistic interactions with dopamine D2 receptors (D2Rs. In one type of interaction, A2AR and D2R are forming heteromers and, by means of an allosteric interaction, A2AR counteracts D2R-mediated inhibitory modulation of the effects of NMDA receptor stimulation in the striato-pallidal neuron. This interaction is probably mostly responsible for the locomotor depressant and activating effects of A2AR agonist and antagonists, respectively. The second type of interaction involves A2AR and D2R that do not form heteromers and takes place at the level of adenylyl-cyclase (AC. Due to a strong tonic effect of endogenous dopamine on striatal D2R, this interaction keeps A2AR from signaling through AC. However, under conditions of dopamine depletion or with blockade of D2R, A2AR-mediated AC activation is unleashed with an increased gene expression and activity of the striato-pallidal neuron and with a consequent motor depression. This interaction is probably the main mechanism responsible for the locomotor depression induced by D2R antagonists. Finally, striatal A2ARs are also localized presynaptically, in cortico-striatal glutamatergic terminals that contact the striato-nigral MSN. These presynaptic A2ARs heteromerize with A1 receptors (A1Rs and their activation facilitates glutamate release. These three different types of A2ARs can be pharmacologically dissected by their ability to bind ligands with different affinity and can therefore provide selective targets for drug development in different basal ganglia disorders.

  13. The Sport League's Dilemma: Competitive Balance versus Incentives to Win.

    OpenAIRE

    Frederic Palomino and Luca Rigotti.

    2000-01-01

    We analyze a dynamic model of strategic interaction between a professional sport league that organizes a tournament, the teams competing to win it, and the broadcasters paying for the rights to televise it. Teams and broadcasters maximize expected profits, while the league's objective may be either to maximize the demand for the sport or to maximize the teams' joint profits. Demand depends positively on symmetry among teams (competitive balance) and how aggressively teams try to win (incentiv...

  14. The Sport League's Dilemma: Competitive Balance versus Incentives to Win

    OpenAIRE

    Palomino, F.A.; Rigotti, L.

    2000-01-01

    We analyze a dynamic model of strategic interaction between a professional sport league that organizes a tournament, the teams competing to win it, and the broadcasters paying for the rights to televise it. Teams and broadcasters maximize expected profits, while the league's objective may be either to maximize the demand for the sport or to maximize the teams' joint profits. Demand depends positively on symmetry among teams (competitive balance) and how aggressively teams try to win (incenti...

  15. How Insurgents Win: Examining the Dynamics of Modern Insurgencies

    Science.gov (United States)

    2014-06-01

    Insurgent Loss Uganda (ADF) 1986–2000 Insurgent Loss Papua New Guinea 1988–1998 Insurgent Win Liberia 1989–1997 Insurgent Win Moldova 1990–1992...of information is estimated to average 1 hour per response, including the time for reviewing instruction, searching existing data sources, gathering ... New York: Cambridge University Press, 2012). 2 and more resources to manipulating the perception of the population, which in turn will allow the

  16. Who Wins the Olympic Games: Economic Development and Medal Totals

    OpenAIRE

    Andrew B. Bernard; Meghan R. Busse

    2000-01-01

    This paper examines determinants of Olympic success at the country level. Does the U.S. win its fair share of Olympic medals? Why does China win 6% of the medals even though it has 1/5 of the world's population? We consider the role of population and economic development in determining medal totals from 1960-1996. We also provide out of sample predictions for the 2000 Olympics in Sydney.

  17. Win a lift to the future!

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    The Communication Group is organising a competition offering people at CERN the chance to submit their ideas and win a ticket to the Lift10 Conference, which will be held in Geneva from 5 to7 May.   Lift is a community of technology "pioneers", created in 2006. It now involves more than 4,000 people from over 60 countries, who meet regularly in Europe and in Asia to explore the social implications of new technologies and the major shifts ahead. CERN is one of the academic partners of the next Lift conference, whose theme is "Connected people”. For this occasion, 10 free tickets to the conference will be awarded to the "CERNois" who come up with the best answers to the question: “How would you contribute to Lift10?” Those taking part in the competition can choose from among the following categories: - run workshop(s); - cover the conference on a blog; - coordinate a discussion during the breaks; - organize a lift@home ...

  18. CERN repeats last year's running win

    CERN Multimedia

    2000-01-01

    The CERN first team successfully defended the title won last year in the 20th annual Cross Inter-Entreprises held at Collex-Bossy on Saturday 7 October. 101 teams of four runners representing firms from all over the Geneva area finished the 6.2 km race, through forest and over fields. In spite of two members of last year’s winning team being absent through injury this time, the first team was still 38 seconds faster than in 1999. The second and third CERN teams also excelled with places in the first 15 teams. In this race the teams start at one-minute intervals and the time of each team is that of its third runner to finish, so they try to run in a group of three or four all the way. The full results of all teams can be found at: http://www.Club-association.ch/CHP Placings of the CERN teams 1st 21:53 Cornelis, Ecarnot, Ehmele, Nisbet 6th 22:50 Cornet, Eklund, Rick, Ruiz Llamas 13th 24:24 Dunkel, Guillot, Montejo Raez, Zamiatin 35th 28:22 Cameron, Galbraith, Revol, Scalisi

  19. Building a winning electric utility organization

    Energy Technology Data Exchange (ETDEWEB)

    Farha, G.; Silverman, L. [McKinsey & Co., Washington, DC (United States); Keough, K. [McKinsey & Co., Cleveland, OH (United States)

    1996-08-01

    The key factor that will differentiate the winners and losers is the speed with which they build their skills and enhance their performance focus. Setting the {open_quote}right{close_quote} aspirations, then effectively managing the change process, will be critical for winning power companies. Historically, only certain dimensions of organizational performance have been critical to an electric utility`s financial success. As a result, utilities understandably focused on achieving high levels of customer satisfaction and reliability, excellent regulatory relationships, and safe and environmentally acceptable operations. However, as the power industry undergoes fundamental change, obtaining superior organizational performance will become much more crucial and difficult. Given the importance of meeting these organizational challenges head on, the authors believe CEOs can only address them by taking an important step back from day-to-day activities to define what high performance really means in the future competitive world and what steps should be taken to achieve their aspirations. To facilitate this rethink - which senior managers should view as a multiyear process - utilities need to do three things in an iterative way: (1) energize the transformation with the right performance aspirations. (2) Tailor a coherent change program to the company`s unique starting position. (3) Manage the change process to build a skill-based and performance-focused organization.

  20. Achieving ecological restoration by working with local people: a Chinese scholar seeks win-win paths

    Directory of Open Access Journals (Sweden)

    Heran Zheng

    2014-09-01

    Full Text Available Environmental degradation and poverty are linked, and this means that conservation and poverty reduction must be tackled together. However, finding a successful integrated strategy has been an elusive goal. We describe the career of a Chinese scholar, Shixiong Cao, whose persistent efforts to find and follow win-win paths have led to ecological restoration accompanied by long-term benefits for local residents. Cao's story illustrates how development that combines environmental and economic perspectives can both help people to escape the poverty trap and restore degraded environments. His experience demonstrates that when environmental managers find solutions that can mitigate or eliminate poverty through the development of green enterprises, they can combine them with environmental restoration efforts to produce long-term sustainable solutions. In this paper, we share Cao's 28 years of experience because we believe that his scientific and practical spirit, and his belief that it is necessary to work directly with the people affected by environmental projects, will inspire other scholars and practitioners to achieve similar successes.

  1. Ombud's Corner: fellows and students – a win-win equation

    CERN Multimedia

    Sudeshna Datta-Cockerill

    2014-01-01

    The hundreds of Fellows and students working at CERN bring precious new blood into the Laboratory. At the same time, CERN offers them invaluable work experience that will have a significant impact on their future careers. It is important that we all work together to make this a win-win situation with lasting positive effects for all concerned over the years to come.   Fellows and students are just setting out on a great professional adventure.  Some of them are very young, others are a bit more experienced … and what happens during this early period can have vast consequences on their approach to work and indeed on their overall careers. They all come here with their hard earned skills and a high degree of motivation, ready to make the most out of an internship at CERN. Sometimes, they are called to integrate into well-established units; at other times, they are asked to join complex collaborations. Almost always they have to deal with new information, new cultures, new t...

  2. International cooperation for nuclear science and energy development- A win win perspective

    International Nuclear Information System (INIS)

    Sheriffah Noor Khamseah Al-Idid Syed Ahmad Idid

    2013-01-01

    Full-text: International and regional cooperation is fundamental for the safe and effective introduction and expansion of nuclear power programme (NPP). A win-win situation can be harnessed as experienced countries in NPP are able to offer a myriad of benefits to new comer countries as well as countries planning for NPP whilst new comer countries are able to offer education and training opportunities and business opportunities to advanced countries in NPP. Countries with long experience in nuclear power programme (NPP) are able to offer experience, knowledge, advisory as well as sharing of resources and facilities with new comer countries. As skilled and competent personnel in the entire nuclear value-chain are critical to support NPP, this paper will provide an overview of some of the experience and resources of advanced countries in NPP that could be shared with new comer countries, with a focus in the area of education and training, as well as in industrial development. The paper will conclude by offering some recommendations as a way forward for establishing international cooperation in Nuclear Education and Training, as well as for industrial development. (author)

  3. 3-Nitropropionic acid neurotoxicity in organotypic striatal and corticostriatal slice cultures is dependent on glucose and glutamate

    DEFF Research Database (Denmark)

    Storgaard, J; Kornblit, B T; Zimmer, J

    2000-01-01

    Mitochondrial inhibition by 3-nitropropionic acid (3-NPA) causes striatal degeneration reminiscent of Huntington's disease. We studied 3-NPA neurotoxicity and possible indirect excitotoxicity in organotypic striatal and corticostriatal slice cultures. Neurotoxicity was quantified by assay...

  4. Cosmic Bubble Image Wins NRAO Contest

    Science.gov (United States)

    2006-10-01

    A striking image of an enormous bubble blown into the dusty gas disk of our own Milky Way galaxy has won first place in the National Radio Astronomy Observatory's second annual Radio Astronomy Image Contest. Dr. Jayanne English of the University of Manitoba led the team that made the winning image using data from the National Science Foundation's Very Large Array (VLA) in New Mexico and Robert C. Byrd Green Bank Telescope (GBT) in West Virginia. Cosmic Bubble Image Giant "Bubble" in Milky Way's Gas CREDIT: English et al., NRAO/AUI/NSF Click on image for large files and full information English and her collaborators Jeroen Stil and Russ Taylor, from the University of Calgary, will share the grand prize of $1,000 from Associated Universities, Inc., the research corporation that operates the observatory for the NSF. "We congratulate Dr. English for producing an outstanding image that beautifully illustrates the power of our radio telescopes," said NRAO Director Fred K.Y. Lo. The image contest is part of a broader NRAO effort to make radio astronomical data and images easily accessible and widely available to scientists, students, teachers, the general public, news media and science-education professionals. That effort includes an expanding image gallery on the observatory's Web site. English's winning image shows a giant bubble in the Milky Way's dusty gas disk. The bubble has been sculpted by the wind and radiation force from a few dozen hot, massive stars along with the explosive force of supernova explosions from dying stars. The bubble, seen in the faint radio glow of hydrogen gas, is some 30,000 light-years from Earth and measures 1,100 by 520 light-years. If the bubble, in the constellation Vulpecula, were visible to human eyes, it would appear to be eight times the diameter of the full Moon in the sky. The image was made using data collected as part of the VLA Galactic Plane Survey (VGPS), a set of systematic observations of the Milky Way. This survey, led by

  5. Adenosine–cannabinoid receptor interactions. Implications for striatal function

    Science.gov (United States)

    Ferré, Sergi; Lluís, Carme; Justinova, Zuzana; Quiroz, César; Orru, Marco; Navarro, Gemma; Canela, Enric I; Franco, Rafael; Goldberg, Steven R

    2010-01-01

    Adenosine and endocannabinoids are very ubiquitous non-classical neurotransmitters that exert a modulatory role on the transmission of other more ‘classical’ neurotransmitters. In this review we will focus on their common role as modulators of dopamine and glutamate neurotransmission in the striatum, the main input structure of the basal ganglia. We will pay particular attention to the role of adenosine A2A receptors and cannabinoid CB1 receptors. Experimental results suggest that presynaptic CB1 receptors interacting with A2A receptors in cortico-striatal glutamatergic terminals that make synaptic contact with dynorphinergic medium-sized spiny neurons (MSNs) are involved in the motor-depressant and addictive effects of cannabinoids. On the other hand, postsynaptic CB1 receptors interacting with A2A and D2 receptors in the dendritic spines of enkephalinergic MSNs and postsynaptic CB1 receptors in the dendritic spines of dynorphinergic MSN are probably involved in the cataleptogenic effects of cannabinoids. These receptor interactions most probably depend on the existence of a variety of heteromers of A2A, CB1 and D2 receptors in different elements of striatal spine modules. Drugs selective for the different striatal A2A and CB1 receptor heteromers could be used for the treatment of neuropsychiatric disorders and drug addiction and they could provide effective drugs with fewer side effects than currently used drugs. This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476-5381.2010.00831.x PMID:20590556

  6. Striatal degeneration impairs language learning: evidence from Huntington's disease.

    Science.gov (United States)

    De Diego-Balaguer, R; Couette, M; Dolbeau, G; Dürr, A; Youssov, K; Bachoud-Lévi, A-C

    2008-11-01

    Although the role of the striatum in language processing is still largely unclear, a number of recent proposals have outlined its specific contribution. Different studies report evidence converging to a picture where the striatum may be involved in those aspects of rule-application requiring non-automatized behaviour. This is the main characteristic of the earliest phases of language acquisition that require the online detection of distant dependencies and the creation of syntactic categories by means of rule learning. Learning of sequences and categorization processes in non-language domains has been known to require striatal recruitment. Thus, we hypothesized that the striatum should play a prominent role in the extraction of rules in learning a language. We studied 13 pre-symptomatic gene-carriers and 22 early stage patients of Huntington's disease (pre-HD), both characterized by a progressive degeneration of the striatum and 21 late stage patients Huntington's disease (18 stage II, two stage III and one stage IV) where cortical degeneration accompanies striatal degeneration. When presented with a simplified artificial language where words and rules could be extracted, early stage Huntington's disease patients (stage I) were impaired in the learning test, demonstrating a greater impairment in rule than word learning compared to the 20 age- and education-matched controls. Huntington's disease patients at later stages were impaired both on word and rule learning. While spared in their overall performance, gene-carriers having learned a set of abstract artificial language rules were then impaired in the transfer of those rules to similar artificial language structures. The correlation analyses among several neuropsychological tests assessing executive function showed that rule learning correlated with tests requiring working memory and attentional control, while word learning correlated with a test involving episodic memory. These learning impairments significantly

  7. Mechanisms mediating parallel action monitoring in fronto-striatal circuits.

    Science.gov (United States)

    Beste, Christian; Ness, Vanessa; Lukas, Carsten; Hoffmann, Rainer; Stüwe, Sven; Falkenstein, Michael; Saft, Carsten

    2012-08-01

    Flexible response adaptation and the control of conflicting information play a pivotal role in daily life. Yet, little is known about the neuronal mechanisms mediating parallel control of these processes. We examined these mechanisms using a multi-methodological approach that integrated data from event-related potentials (ERPs) with structural MRI data and source localisation using sLORETA. Moreover, we calculated evoked wavelet oscillations. We applied this multi-methodological approach in healthy subjects and patients in a prodromal phase of a major basal ganglia disorder (i.e., Huntington's disease), to directly focus on fronto-striatal networks. Behavioural data indicated, especially the parallel execution of conflict monitoring and flexible response adaptation was modulated across the examined cohorts. When both processes do not co-incide a high integrity of fronto-striatal loops seems to be dispensable. The neurophysiological data suggests that conflict monitoring (reflected by the N2 ERP) and working memory processes (reflected by the P3 ERP) differentially contribute to this pattern of results. Flexible response adaptation under the constraint of high conflict processing affected the N2 and P3 ERP, as well as their delta frequency band oscillations. Yet, modulatory effects were strongest for the N2 ERP and evoked wavelet oscillations in this time range. The N2 ERPs were localized in the anterior cingulate cortex (BA32, BA24). Modulations of the P3 ERP were localized in parietal areas (BA7). In addition, MRI-determined caudate head volume predicted modulations in conflict monitoring, but not working memory processes. The results show how parallel conflict monitoring and flexible adaptation of action is mediated via fronto-striatal networks. While both, response monitoring and working memory processes seem to play a role, especially response selection processes and ACC-basal ganglia networks seem to be the driving force in mediating parallel conflict

  8. Neuroinflammation alters voltage-dependent conductance in striatal astrocytes.

    Science.gov (United States)

    Karpuk, Nikolay; Burkovetskaya, Maria; Kielian, Tammy

    2012-07-01

    Neuroinflammation has the capacity to alter normal central nervous system (CNS) homeostasis and function. The objective of the present study was to examine the effects of an inflammatory milieu on the electrophysiological properties of striatal astrocyte subpopulations with a mouse bacterial brain abscess model. Whole cell patch-clamp recordings were performed in striatal glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP)(+) astrocytes neighboring abscesses at postinfection days 3 or 7 in adult mice. Cell input conductance (G(i)) measurements spanning a membrane potential (V(m)) surrounding resting membrane potential (RMP) revealed two prevalent astrocyte subsets. A1 and A2 astrocytes were identified by negative and positive G(i) increments vs. V(m), respectively. A1 and A2 astrocytes displayed significantly different RMP, G(i), and cell membrane capacitance that were influenced by both time after bacterial exposure and astrocyte proximity to the inflammatory site. Specifically, the percentage of A1 astrocytes was decreased immediately surrounding the inflammatory lesion, whereas A2 cells were increased. These changes were particularly evident at postinfection day 7, revealing increased cell numbers with an outward current component. Furthermore, RMP was inversely modified in A1 and A2 astrocytes during neuroinflammation, and resting G(i) was increased from 21 to 30 nS in the latter. In contrast, gap junction communication was significantly decreased in all astrocyte populations associated with inflamed tissues. Collectively, these findings demonstrate the heterogeneity of striatal astrocyte populations, which experience distinct electrophysiological modifications in response to CNS inflammation.

  9. Impaired striatal Akt signaling disrupts dopamine homeostasis and increases feeding.

    Directory of Open Access Journals (Sweden)

    Nicole Speed

    Full Text Available The prevalence of obesity has increased dramatically worldwide. The obesity epidemic begs for novel concepts and therapeutic targets that cohesively address "food-abuse" disorders. We demonstrate a molecular link between impairment of a central kinase (Akt involved in insulin signaling induced by exposure to a high-fat (HF diet and dysregulation of higher order circuitry involved in feeding. Dopamine (DA rich brain structures, such as striatum, provide motivation stimuli for feeding. In these central circuitries, DA dysfunction is posited to contribute to obesity pathogenesis. We identified a mechanistic link between metabolic dysregulation and the maladaptive behaviors that potentiate weight gain. Insulin, a hormone in the periphery, also acts centrally to regulate both homeostatic and reward-based HF feeding. It regulates DA homeostasis, in part, by controlling a key element in DA clearance, the DA transporter (DAT. Upon HF feeding, nigro-striatal neurons rapidly develop insulin signaling deficiencies, causing increased HF calorie intake.We show that consumption of fat-rich food impairs striatal activation of the insulin-activated signaling kinase, Akt. HF-induced Akt impairment, in turn, reduces DAT cell surface expression and function, thereby decreasing DA homeostasis and amphetamine (AMPH-induced DA efflux. In addition, HF-mediated dysregulation of Akt signaling impairs DA-related behaviors such as (AMPH-induced locomotion and increased caloric intake. We restored nigro-striatal Akt phosphorylation using recombinant viral vector expression technology. We observed a rescue of DAT expression in HF fed rats, which was associated with a return of locomotor responses to AMPH and normalization of HF diet-induced hyperphagia.Acquired disruption of brain insulin action may confer risk for and/or underlie "food-abuse" disorders and the recalcitrance of obesity. This molecular model, thus, explains how even short-term exposure to "the fast food

  10. Association Between Peripheral Inflammation and DATSCAN Data of the Striatal Nuclei in Different Motor Subtypes of Parkinson Disease

    Directory of Open Access Journals (Sweden)

    Hossein Sanjari Moghaddam

    2018-04-01

    Full Text Available The interplay between peripheral and central inflammation has a significant role in dopaminergic neural death in nigrostriatal pathway, although no direct assessment of inflammation has been performed in relation to dopaminergic neuronal loss in striatal nuclei. In this study, the correlation of neutrophil to lymphocyte ratio (NLR as a marker of peripheral inflammation to striatal binding ratios (SBRs of DAT SPECT images in bilateral caudate and putamen nuclei was calculated in 388 drug-naïve early PD patients [288 tremor dominant (TD, 73 postural instability and gait difficulty (PIGD, and 27 indeterminate] and 148 controls. NLR was significantly higher in PD patients than in age- and sex-matched healthy controls, and showed a negative correlation to SBR in bilateral putamen and ipsilateral caudate in all PD subjects. Among our three subgroups, only TD patients showed remarkable results. A positive association between NLR and motor severity was observed in TD subgroup. Besides, NLR could negatively predict the SBR in ipsilateral and contralateral putamen and caudate nuclei in tremulous phenotype. Nonetheless, we found no significant association between NLR and other clinical and imaging findings in PIGD and indeterminate subgroups, supporting the presence of distinct underlying pathologic mechanisms between tremor and non-tremor predominant PD at early stages of the disease.

  11. Study on dopamine D{sub 2} binding capacity in vascular parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Terashi, Hiroo; Nagata, Ken; Hirata, Yutaka; Hatazawa, Jun [Research Inst. for Brain and Blood Vessels, Akita (Japan); Utsumi, Hiroya [Tokyo Medical Coll. (Japan)

    2001-10-01

    To investigate whether the striatal dopamine receptor function is involved in the development of vascular parkinsonism (VP), a positron emission tomography (PET) study was conducted on 9 patients with VP by using [{sup 11}C] N-methylspiperone as the tracer. The rate of binding availability in the striatal dopamine D{sub 2} receptor (k{sub 3}) was determined semiquantitatively, and the values were compared to the predicted normal values based on the results from 7 normal volunteers. Of 9 patients with VP, the normalized D{sub 2} receptor binding [%k{sub 3}] was more than 90% in 5 patients, 89 to 87% in 3, and 75% in one. These values showed no evident correlation with the Hoehn and Yahr stage. The laterality of the striatal %k{sub 3} did not correspond to that of the parkinsonism. Thus, the striatal dopamine D{sub 2} receptor binding was not severely impaired and did not correlate with the neurological status in patients with VP. This may indicate that striatal dopamine D{sub 2} receptor function is not primarily associated with the development of the parkinsonism in VP. (author)

  12. Cognitive emotion regulation modulates the balance of competing influences on ventral striatal aversive prediction error signals.

    Science.gov (United States)

    Mulej Bratec, Satja; Xie, Xiyao; Wang, Yijun; Schilbach, Leonhard; Zimmer, Claus; Wohlschläger, Afra M; Riedl, Valentin; Sorg, Christian

    2017-02-15

    Cognitive emotion regulation (CER) is a critical human ability to face aversive emotional stimuli in a flexible way, via recruitment of specific prefrontal brain circuits. Animal research reveals a central role of ventral striatum in emotional behavior, for both aversive conditioning, with striatum signaling aversive prediction errors (aPE), and for integrating competing influences of distinct striatal inputs from regions such as the prefrontal cortex (PFC), amygdala, hippocampus and ventral tegmental area (VTA). Translating these ventral striatal findings from animal research to human CER, we hypothesized that successful CER would affect the balance of competing influences of striatal afferents on striatal aPE signals, in a way favoring PFC as opposed to 'subcortical' (i.e., non-isocortical) striatal inputs. Using aversive Pavlovian conditioning with and without CER during fMRI, we found that during CER, superior regulators indeed reduced the modulatory impact of 'subcortical' striatal afferents (hippocampus, amygdala and VTA) on ventral striatal aPE signals, while keeping the PFC impact intact. In contrast, inferior regulators showed an opposite pattern. Our results demonstrate that ventral striatal aPE signals and associated competing modulatory inputs are critical mechanisms underlying successful cognitive regulation of aversive emotions in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD and Alzheimer's disease (AD

    Directory of Open Access Journals (Sweden)

    Dong Seok Yi

    Full Text Available ABSTRACT Behavioural disturbances in frontotemporal dementia (FTD are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. Objective: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. Methods: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R and Frontal System Behaviour Scale (FrSBe. Atrophy in prefrontal (VMPFC, DLPFC and striatal (caudate, putamen regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. Results: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. Conclusion: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

  14. Reciprocal influences of nigral cells and striatal patch neurons in dissociated co-cultures

    NARCIS (Netherlands)

    Aronica, E.; Costantini, L. C.; Snyder-Keller, A.

    1996-01-01

    Our previous work has shown that the functional efficacy of nigral tissue transplants into dopamine (DA)-depleted rats is increased when embryonic striatal tissue is included (Costantini et al.: Exp Neurol 127:219-231, 1994). To examine further the influence of striatal patch neurons in this regard,

  15. GABAERGIC MODULATION OF STRIATAL CHOLINERGIC INTERNEURONS - AN IN-VIVO MICRODIALYSIS STUDY

    NARCIS (Netherlands)

    DEBOER, P; WESTERINK, BHC

    Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABA(A) and the GABA(B) receptor. Using in vivo microdialysis, we have studied the effect of

  16. Striatal and extrastriatal imaging of dopamine D2receptors in the living human brain with [ 123I[epidepride single-photon emission tomography

    International Nuclear Information System (INIS)

    Kuikka, J.T.; Aakerman, K.K.; Hiltunen, J.; Bergstroem, K.A.; Raesaenen, P.; Vanninen, E.; Halldin, C.; Tiihonen, J.

    1997-01-01

    The iodine-123 labelled ligand benzamide epidepride was evaluated as a probe for in vivo imaging of striatal and extrastriatal dopamine D 2 receptor sites in the human brain. Four healthy males were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 3 h after injection. The specific binding in the striatum was 0.91 ±0.03 at 3 h and this ratio steadily increased with time. Extrastriatal radioactivity was highest in the thalamus, in the midbrain and in the temporal cortex, and peaked at 45-60 min after injection of tracer. A smaller amount of radioactivity was found in the parietal, frontal and occipital cortices. Two radioactive metabolites were observed, of which one was more lipophilic than the parent compound. The radiation burden to the patient was 0.035 mSv/MBq (effective dose equivalent). The preliminary results showed that [ 123 I[epidepride can be used for imaging striatal and extrastriatal dopamine D 2 receptor sites in the living human brain. (orig.). With 5 figs., 1 tab

  17. WINS. Market Simulation Tool for Facilitating Wind Energy Integration

    Energy Technology Data Exchange (ETDEWEB)

    Shahidehpour, Mohammad [Illinois Inst. of Technology, Chicago, IL (United States)

    2012-10-30

    Integrating 20% or more wind energy into the system and transmitting large sums of wind energy over long distances will require a decision making capability that can handle very large scale power systems with tens of thousands of buses and lines. There is a need to explore innovative analytical and implementation solutions for continuing reliable operations with the most economical integration of additional wind energy in power systems. A number of wind integration solution paths involve the adoption of new operating policies, dynamic scheduling of wind power across interties, pooling integration services, and adopting new transmission scheduling practices. Such practices can be examined by the decision tool developed by this project. This project developed a very efficient decision tool called Wind INtegration Simulator (WINS) and applied WINS to facilitate wind energy integration studies. WINS focused on augmenting the existing power utility capabilities to support collaborative planning, analysis, and wind integration project implementations. WINS also had the capability of simulating energy storage facilities so that feasibility studies of integrated wind energy system applications can be performed for systems with high wind energy penetrations. The development of WINS represents a major expansion of a very efficient decision tool called POwer Market Simulator (POMS), which was developed by IIT and has been used extensively for power system studies for decades. Specifically, WINS provides the following superiorities; (1) An integrated framework is included in WINS for the comprehensive modeling of DC transmission configurations, including mono-pole, bi-pole, tri-pole, back-to-back, and multi-terminal connection, as well as AC/DC converter models including current source converters (CSC) and voltage source converters (VSC); (2) An existing shortcoming of traditional decision tools for wind integration is the limited availability of user interface, i.e., decision

  18. Winning and positive affect can lead to reckless gambling.

    Science.gov (United States)

    Cummins, Lori F; Nadorff, Michael R; Kelly, Anita E

    2009-06-01

    Experiments 1 and 2 examined whether winning versus losing led to reckless betting for real prize money. Experiment 2 also assessed whether positive or negative emotions were linked to such reckless betting. College students were randomly assigned to experience primarily either wins or losses during the rigged first round of a computerized card tournament that had 2 independent rounds. For the second round, participants' chip totals were reset and cards were dealt randomly. In Experiment 1 (N=107), participants in the Initial-Winning, as compared with the Initial-Losing, condition bet more recklessly (i.e., bet too many chips when a loss was likely). Experiment 2 (N=72) again showed that Initial-Winning participants bet significantly more recklessly than did Initial-Losing participants. It also revealed that positive affect was significantly positively correlated with such reckless betting. These findings have implications for understanding how college students, those at an age when they are especially vulnerable to problem gambling, can come to lose more money than they can afford. Initially winning and positive affect when gambling could be risk factors. Copyright (c) 2009 APA, all rights reserved.

  19. Winning at litigation through decision analysis creating and executing winning strategies in any litigation or dispute

    CERN Document Server

    Celona, John

    2016-01-01

    This book is the first in-depth guide to applying the philosophy, theory, and methods of decision analysis to creating and executing winning legal strategies. With explanations that progress from introductory to advanced and practice problems at the end of each chapter, this is a book the reader will want to use and refer to for years to come. Practicing decision analysts, operations research and management science students, attorneys and law students will find this book an invaluable addition to their knowledge and skills. John Celona has over three decades of experience in teaching and applying decision analysis. John lectures in the School of Engineering at Stanford University and is on faculty at The Stanford Center for Professional Development, the American Course on Drug Development and Regulatory Sciences, and the Academy of the American Society for Healthcare Risk Management.

  20. Winning at Pocker and Games of Chance Winning at Pocker and Games of Chance

    Directory of Open Access Journals (Sweden)

    Anita Flanders Rebelo

    2008-04-01

    Full Text Available It's the modern consumer mind - compete to eat, save to the grave, throw to the wind to win! Never the game that's im portant - it's the beer , the fag. . . and if you're broke it's just the "odds" to turn you on. "Socrates didn't play dice games. He drank a lot. And when he was drunk he would go watch the game and give advice. It was because of bad advice that he was eventually sentenced to death. . . Back then it was more fun. Nobody knew anything about odds. It was just put down your money, you toss the dice, you laugh, you take another drink." - to Cassidy,it's knowing the odds that's put everybody on pot. Rack Cassidy's Winning at Poker and Games of Chance lampoons the illogic logic of modern "instructed" man. It is a disturbingly funny caricature of a nonsensical consumer's mind trying to ratio nalize the game of life, and what comes out is "hash" - not meat and potatoes. The book is high philosophical slapstick comedy ila Charlie Chaplin on paper in today's scene. To Cassidy, consumer thinking has made intellectual nitwits of us. We're always ex plaining in detail about what we don't have the slightest real understanding of, but we go on and on like automats spitting out words and words which in the long run make no sense to our__ selves and much less to the other poor broken down human calculat ing machines - especially when we try to give logic to our il/logical vices and fears.

  1. Predicting treatment response in Schizophrenia: the role of stratal and frontal dopamine D2/D3 receptor binding potential

    DEFF Research Database (Denmark)

    Wulff, Sanne; Nørbak-Emig, Henrik; Nielsen, Mette Ødegaard

    2014-01-01

    relationship between frontal and striatal dopamine activity. Data also emphasize that there might be gender differences. The data analysis is ongoing. (1) Glenthøj BY, Mackeprang T et al. Frontal dopamine D2/3 receptor binding in drug-naïve first-episode schizophrenic patients correlates with positive...... cortex in antipsychotic-naïve first-episode male schizophrenia patients(1). Preclinical studies suggest an inverse relationship between frontal and striatal dopamine activity. This activity can indirectly be expressed by the BP of dopamine receptors using Single Photon Emission Computed Tomography (SPECT......-up. There was a negative correlation between striatal BP and improvement of the PANSS total score (Rho=-0,553 P=0.009). Furthermore we found a negative correlation between striatal BP and improvement of positive symptoms among the male patients only (P=0.020). The same relationship was found at trend level for the entire...

  2. Connes' embedding problem and winning strategies for quantum XOR games

    Science.gov (United States)

    Harris, Samuel J.

    2017-12-01

    We consider quantum XOR games, defined in the work of Regev and Vidick [ACM Trans. Comput. Theory 7, 43 (2015)], from the perspective of unitary correlations defined in the work of Harris and Paulsen [Integr. Equations Oper. Theory 89, 125 (2017)]. We show that the winning bias of a quantum XOR game in the tensor product model (respectively, the commuting model) is equal to the norm of its associated linear functional on the unitary correlation set from the appropriate model. We show that Connes' embedding problem has a positive answer if and only if every quantum XOR game has entanglement bias equal to the commuting bias. In particular, the embedding problem is equivalent to determining whether every quantum XOR game G with a winning strategy in the commuting model also has a winning strategy in the approximate finite-dimensional model.

  3. The sigma-1 receptor modulates dopamine transporter conformation and cocaine binding and may thereby potentiate cocaine self-administration in rats.

    Science.gov (United States)

    Hong, Weimin Conrad; Yano, Hideaki; Hiranita, Takato; Chin, Frederick T; McCurdy, Christopher R; Su, Tsung-Ping; Amara, Susan G; Katz, Jonathan L

    2017-07-07

    The dopamine transporter (DAT) regulates dopamine (DA) neurotransmission by recapturing DA into the presynaptic terminals and is a principal target of the psychostimulant cocaine. The sigma-1 receptor (σ 1 R) is a molecular chaperone, and its ligands have been shown to modulate DA neuronal signaling, although their effects on DAT activity are unclear. Here, we report that the prototypical σ 1 R agonist (+)-pentazocine potentiated the dose response of cocaine self-administration in rats, consistent with the effects of the σR agonists PRE-084 and DTG (1,3-di- o -tolylguanidine) reported previously. These behavioral effects appeared to be correlated with functional changes of DAT. Preincubation with (+)-pentazocine or PRE-084 increased the B max values of [ 3 H]WIN35428 binding to DAT in rat striatal synaptosomes and transfected cells. A specific interaction between σ 1 R and DAT was detected by co-immunoprecipitation and bioluminescence resonance energy transfer assays. Mutational analyses indicated that the transmembrane domain of σ 1 R likely mediated this interaction. Furthermore, cysteine accessibility assays showed that σ 1 R agonist preincubation potentiated cocaine-induced changes in DAT conformation, which were blocked by the specific σ 1 R antagonist CM304. Moreover, σ 1 R ligands had distinct effects on σ 1 R multimerization. CM304 increased the proportion of multimeric σ 1 Rs, whereas (+)-pentazocine increased monomeric σ 1 Rs. Together these results support the hypothesis that σ 1 R agonists promote dissociation of σ 1 R multimers into monomers, which then interact with DAT to stabilize an outward-facing DAT conformation and enhance cocaine binding. We propose that this novel molecular mechanism underlies the behavioral potentiation of cocaine self-administration by σ 1 R agonists in animal models. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Winning the jackpot and depression: Money cannot buy happiness.

    Science.gov (United States)

    Nisslé, Sonja; Bschor, Tom

    2002-01-01

    Life event research examines the effect of life events on the course of psychiatric diseases, but the published literature considers almost only negative events. We describe the cases of two female patients who had to be hospitalized for depression after lottery winnings of over 1M DM. The 4-year follow-up shows a good outcome in both patients. Case analyses suggest that in both patients, winning was a life event relevant to the development of the depressive episode. Desirable life events might influence the course of a psychiatric illness just as negative events do. (Int J Psych Clin Pract 2002; 6: 183-186).

  5. BMC Ecology image competition 2014: the winning images

    Science.gov (United States)

    2014-01-01

    BMC Ecology showcases the winning entries from its second Ecology Image Competition. More than 300 individual images were submitted from an international array of research scientists, depicting life on every continent on earth. The journal’s Editorial Board and guest judge Caspar Henderson outline why their winning selections demonstrated high levels of technical skill and aesthetic sense in depicting the science of ecology, and we also highlight a small selection of highly commended images that we simply couldn’t let you miss out on. PMID:25178017

  6. Measurement of striatal dopamine metabolism with 6-[18F]-fluoro-L-dopa and PET

    International Nuclear Information System (INIS)

    Kuwabara, Y.; Otsuka, M.; Ichiya, Y.; Yoshikai, T.; Fukumura, T.; Masuda, K.; Kato, M.; Taniwaki, T.

    1992-01-01

    Striatal dopamine metabolism was studied with 6-[ 18 F]-fluoro-L-dopa ( 18 F-DOPA) and PET. The subjects were normal controls, and patients with Parkinson's disease (PD), parkinsonism, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Alzheimer's disease (AD), Huntington's disease (HD) and other cerebral disorders. Cerebral glucose metabolism (CMRGlc) was also measured in these patients. Striatal dopamine metabolism was evaluated by the relative striatal uptake of 18 F-DOPA referring cerebellum (S/C ratio). In normal controls, the S/C ratio was 2.82 ± 0.32 (n = 6, mean ± SD) at 120 min after injection of 18 F-DOPA. The S/C ratio was low in patients with PD, parkinsonism, MSA and PSP compared to the normal controls and thus coincident with the symptoms of parkinsonism due to decrease in striatal dopamine concentration. The decrease in the striatal CMRGlc was also observed in patients with parkinsonism and PSP, and it was preserved in patients with PD, thus representing that more neurons were damaged in patients with parkinsonism and PSP than in patients with PD. A patient with AD having symptoms of parkinsonism also showed a decrease in S/C ratio. In a patient with HD, the striatal CMRGlc sharply decreased, but the S/C ratio was normal. The measurements of striatal dopamine and glucose metabolism with PET may be useful for studying the pathophysiological mechanism in patients with cerebral disorders. (author)

  7. Dietary Tyrosine Protects Striatal Dopamine Receptors from the Adverse Effects of REM Sleep Deprivation.

    Science.gov (United States)

    Hamdi, A; Brock, J W; Payne, S; Ross, K D; Bond, S P; Prasad, C

    1998-01-01

    L-Tyrosine is a non-essential amino acid that is produced as an intermediary metabolite in the conversion of phenylalanine to 3,4-dihyroxyphenylalanine (DOPA), and is a precursor of the neurotransmitter dopamine. In previous studies, tyrosine pretreatment was shown to protect against the neurochemical and behavioral deficits of acute stress caused by tail shock or cold exposure in rodents. The present study addressed the hypothesis that tyrosine administration may be an effective counter-measure to dopamine-mediated behaviors induced by rapid eye-movement sleep deprivation (RSD). In order to test the hypothesis, Sprague-Dawley rats were divided into 9 treatment groups: RSD-treated rats on normal-protein diet (20% casein: 1% tyrosine, 1% valine); tank control (TC) rats on a normal diet; cage control (CC) rats on normal diet; RSD-treated rats on 4% tyrosine diet; TC rats on 4% tyrosine diet; CC rats on 4% tyrosine diet; RSD-treated rats on 4% valine diet; TC rats on 4% valine diet; CC rats on 4% valine diet. In the RSD group receiving tyrosine, there was no apparent change in Bmax for binding of the dopamine D2 receptor ligand [(3)H]YM-09151-2 in the striata as compared to the respective TC and CC groups; whereas RSD-treated rats maintained on the normal diet and valine supplementation demonstrated expected increases in Bmax for ligand binding. The TC group on the tyrosine diet showed attenuated catalepsy compared to the corresponding CC group, while the RSD group consuming tyrosine showed a catalepsy that was significantly increased, and similar to that of cage control animais on a control diet. These data suggest that the tyrosine-supplemented diet significantly attenuated RSD-induced changes in striatal dopamine D2 receptors, and the effect appeared sufficient to influence RSD-induced behaviors.

  8. Modification of opiate agonist binding by pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-03-05

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in /sup 3/(H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding.

  9. Modification of opiate agonist binding by pertussis toxin

    International Nuclear Information System (INIS)

    Abood, M.E.; Lee, N.M.; Loh, H.H.

    1986-01-01

    Opiate agonist binding is decreased by GTP, suggesting the possible involvement of GTP binding proteins in regulation of opiate receptor binding. This possibility was addressed by asking whether pertussis toxin treatment, which results in ADP-ribosylation and modification of G proteins, would alter opiate agonist binding. The striatum was chosen for the initial brain area to be studied, since regulation of opiate action in this area had been shown to be modified by pertussis toxin. Treatment of striatal membranes with pertussis toxin results in up to a 55% decrease in 3 (H)-DADLE binding as compared with membranes treated identically without toxin. This corresponds to a near complete ADP-ribosylation of both G proteins in the striatal membrane. The decrease in agonist binding appears to be due to an altered affinity of the receptor for agonist as opposed to a decrease in the number of sites. This effect of pertussis toxin on opiate agonist binding demonstrates the actual involvement of G proteins in regulation of opiate receptor binding

  10. Regulation of drugs affecting striatal cholinergic activity by corticostriatal projections

    International Nuclear Information System (INIS)

    Ladinsky, H.

    1986-01-01

    Research demonstrates that the chronic degeneration of the corticostriatal excitatory pathway makes the cholinergic neurons of the striatum insensitive to the neuropharmacological action of a number of different drugs. Female rats were used; they were killed and after the i.v. infusion of tritium-choline precursor, choline acetyltransferase activity was measured. Striatal noradrenaline, dopamine and serotonin content was measured by electrochemical detection coupled with high pressure liquid chromatography. Uptake of tritium-glutamic acid was estimated. The data were analyzed statistically. It is shown that there is evidence that the effects of a number of drugs capable of depressing cholinergic activity through receptor-mediated responses are operative only if the corticostriatal pathway is integral. Neuropharmacological responses in the brain appear to be the result of an interaction between several major neurotransmitter systems

  11. Striatal grafts in a rat model of Huntington's disease

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O

    1999-01-01

    , which was found unaltered for the first 21 days posttransplantation, whereas a hypointense graft signal was detected at 99 days posttransplantation. At 2 days posttransplantation, T2-weighted images showed the graft region as a hyperintense area surrounded by a rim of low signal intensity but at later...... time-points graft location could not be further verified. Measures for graft size and ventricle size obtained from MR images highly correlated with measures obtained from histologically processed sections (R = 0.8, P ...Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...

  12. Astrocytosis in parkinsonism: considering tripartite striatal synapses in physiopathology?

    Science.gov (United States)

    Charron, Giselle; Doudnikoff, Evelyne; Canron, Marie-Helene; Li, Qin; Véga, Céline; Marais, Sebastien; Baufreton, Jérôme; Vital, Anne; Oliet, Stéphane H R; Bezard, Erwan

    2014-01-01

    The current concept of basal ganglia organization and function in physiological and pathophysiological conditions excludes the most numerous cells in the brain, i.e., the astrocytes, present with a ratio of 10:1 neuron. Their role in neurodegenerative condition such as Parkinson's disease (PD) remains to be elucidated. Before embarking into physiological investigations of the yet-to-be-identified "tripartite" synapses in the basal ganglia in general and the striatum in particular, we therefore characterized anatomically the PD-related modifications in astrocytic morphology, the changes in astrocytic network connections and the consequences on the spatial relationship between astrocytic processes and asymmetric synapses in normal and PD-like conditions in experimental and human PD. Our results unravel a dramatic regulation of striatal astrocytosis supporting the hypothesis of a key role in (dys) regulating corticostriatal transmission. Astrocytes and their various properties might thus represent a therapeutic target in PD.

  13. Astrocytosis in parkinsonism: considering tripartite striatal synapses in physiopathology?

    Directory of Open Access Journals (Sweden)

    Giselle eCharron

    2014-09-01

    Full Text Available The current concept of basal ganglia organization and function in physiological and pathophysiological conditions excludes the most numerous cells in the brain, i.e. the astrocytes, present with a ratio of 10:1 neuron. Their role in neurodegenerative condition such as Parkinson’s disease (PD remains to be elucidated. Before embarking into physiological investigations of the yet-to-be-identified tripartite synapses in the basal ganglia in general and the striatum in particular, we therefore characterized anatomically the PD-related modifications in astrocytic morphology, the changes in astrocytic network connections and the consequences on the spatial relationship between astrocytic processes and asymmetric synapses in normal and PD-like conditions in experimental and human PD. Our results unravel a dramatic regulation of striatal astrocytosis supporting the hypothesis of a key role in (dysregulating corticostriatal transmission. Astrocytes and their various properties might thus represent a therapeutic target in PD.

  14. Regulation of bat echolocation pulse acoustics by striatal dopamine.

    Science.gov (United States)

    Tressler, Jedediah; Schwartz, Christine; Wellman, Paul; Hughes, Samuel; Smotherman, Michael

    2011-10-01

    The ability to control the bandwidth, amplitude and duration of echolocation pulses is a crucial aspect of echolocation performance but few details are known about the neural mechanisms underlying the control of these voice parameters in any mammal. The basal ganglia (BG) are a suite of forebrain nuclei centrally involved in sensory-motor control and are characterized by their dependence on dopamine. We hypothesized that pharmacological manipulation of brain dopamine levels could reveal how BG circuits might influence the acoustic structure of bat echolocation pulses. A single intraperitoneal injection of a low dose (5 mg kg(-1)) of the neurotoxin 1-methyl-4-phenylpyridine (MPTP), which selectively targets dopamine-producing cells of the substantia nigra, produced a rapid degradation in pulse acoustic structure and eliminated the bat's ability to make compensatory changes in pulse amplitude in response to background noise, i.e. the Lombard response. However, high-performance liquid chromatography (HPLC) measurements of striatal dopamine concentrations revealed that the main effect of MPTP was a fourfold increase rather than the predicted decrease in striatal dopamine levels. After first using autoradiographic methods to confirm the presence and location of D(1)- and D(2)-type dopamine receptors in the bat striatum, systemic injections of receptor subtype-specific agonists showed that MPTP's effects on pulse acoustics were mimicked by a D(2)-type dopamine receptor agonist (Quinpirole) but not by a D(1)-type dopamine receptor agonist (SKF82958). The results suggest that BG circuits have the capacity to influence echolocation pulse acoustics, particularly via D(2)-type dopamine receptor-mediated pathways, and may therefore represent an important mechanism for vocal control in bats.

  15. Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development.

    Science.gov (United States)

    Forcelli, Patrick A; Janssen, Megan J; Vicini, Stefano; Gale, Karen

    2012-09-01

    Drug exposure during critical periods of brain development may adversely affect nervous system function, posing a challenge for treating infants. This is of particular concern for treating neonatal seizures, as early life exposure to drugs such as phenobarbital is associated with adverse neurological outcomes in patients and induction of neuronal apoptosis in animal models. The functional significance of the preclinical neurotoxicity has been questioned due to the absence of evidence for functional impairment associated with drug-induced developmental apoptosis. We used patch-clamp recordings to examine functional synaptic maturation in striatal medium spiny neurons from neonatal rats exposed to antiepileptic drugs with proapoptotic action (phenobarbital, phenytoin, lamotrigine) and without proapoptotic action (levetiracetam). Phenobarbital-exposed rats were also assessed for reversal learning at weaning. Recordings from control animals revealed increased inhibitory and excitatory synaptic connectivity between postnatal day (P)10 and P18. This maturation was absent in rats exposed at P7 to a single dose of phenobarbital, phenytoin, or lamotrigine. Additionally, phenobarbital exposure impaired striatal-mediated behavior on P25. Neuroprotective pretreatment with melatonin, which prevents drug-induced neurodevelopmental apoptosis, prevented the drug-induced disruption in maturation. Levetiracetam was found not to disrupt synaptic development. Our results provide the first evidence that exposure to antiepileptic drugs during a sensitive postnatal period impairs physiological maturation of synapses in neurons that survive the initial drug insult. These findings suggest a mechanism by which early life exposure to antiepileptic drugs can impact cognitive and behavioral outcomes, underscoring the need to identify therapies that control seizures without compromising synaptic maturation. Copyright © 2012 American Neurological Association.

  16. Improved 123I-Ioflupane Binding After Immunotherapy in Anti-NAE Antibody-Positive Hashimoto Encephalopathy That Clinically Mimicked Multiple System Atrophy.

    Science.gov (United States)

    Otsuka, Juuri; Hida, Ayumi; Ogyu, Kamiyu; Minamimoto, Ryogo; Takeuchi, Sousuke

    2017-08-01

    We describe an 84-year-old man with anti-NH2-terminal of α-enolase antibody-positive Hashimoto encephalopathy that clinically mimicked multiple system atrophy who underwent investigation by dopamine transporter SPECT before and after immunotherapy. Before treatment, dopamine transporter SPECT showed reduced striatal I-ioflupane binding, with a mean specific binding ratio of 2.42, even though he had no apparent parkinsonism. After immunotherapy, mean specific binding ratio was improved to 3.22. Dopamine transporter SPECT was useful in this case to detect subclinical striatal dysfunction, and evaluation both before and after immunotherapy helped to distinguish between neurodegenerative disease and neuroimmunological disorder.

  17. Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: A combined PET, fMRI and DTI study

    Science.gov (United States)

    Simonyan, Kristina; Herscovitch, Peter; Horwitz, Barry

    2013-01-01

    Considerable progress has been recently made in understanding the brain mechanisms underlying speech and language control. However, the neurochemical underpinnings of normal speech production remain largely unknown. We investigated the extent of striatal endogenous dopamine release and its influences on the organization of functional striatal speech networks during production of meaningful English sentences using a combination of positron emission tomography (PET) with the dopamine D2/D3 receptor radioligand [11C]raclopride and functional MRI (fMRI). In addition, we used diffusion tensor tractography (DTI) to examine the extent of dopaminergic modulatory influences on striatal structural network organization. We found that, during sentence production, endogenous dopamine was released in the ventromedial portion of the dorsal striatum, in its both associative and sensorimotor functional divisions. In the associative striatum, speech-induced dopamine release established a significant relationship with neural activity and influenced the left-hemispheric lateralization of striatal functional networks. In contrast, there were no significant effects of endogenous dopamine release on the lateralization of striatal structural networks. Our data provide the first evidence for endogenous dopamine release in the dorsal striatum during normal speaking and point to the possible mechanisms behind the modulatory influences of dopamine on the organization of functional brain circuits controlling normal human speech. PMID:23277111

  18. Aberrant neural signatures of decision-making: Pathological gamblers display cortico-striatal hypersensitivity to extreme gambles.

    Science.gov (United States)

    Gelskov, Sofie V; Madsen, Kristoffer H; Ramsøy, Thomas Z; Siebner, Hartwig R

    2016-03-01

    Pathological gambling is an addictive disorder characterized by an irresistible urge to gamble despite severe consequences. One of the hallmarks of pathological gambling is maladaptive and highly risky decision-making, which has been linked to dysregulation of reward-related brain regions such as the ventral striatum. However, previous studies have produced contradictory results regarding the implication of this network, revealing either hypo- or hypersensitivity to monetary gains and losses. One possible explanation is that the gambling brain might be misrepresenting the benefits and costs when weighting the potential outcomes, and not the gains and losses per se. To address this issue, we investigated whether pathological gambling is associated with abnormal brain activity during decisions that weight the utility of possible gains against possible losses. Pathological gamblers and healthy human subjects underwent functional magnetic resonance imaging while they accepted or rejected mixed gain/loss gambles with fifty-fifty chances of winning or losing. Contrary to healthy individuals, gamblers showed a U-shaped response profile reflecting hypersensitivity to the most appetitive and most aversive bets in an executive cortico-striatal network including the dorsolateral prefrontal cortex and caudate nucleus. This network is concerned with the evaluation of action-outcome contingencies, monitoring recent actions and anticipating their consequences. The dysregulation of this specific network, especially for extreme bets with large potentials consequences, offers a novel understanding of the neural basis of pathological gambling in terms of deficient associations between gambling actions and their financial impact. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Relationship of frontal D2/3 binding potentials to cognition

    DEFF Research Database (Denmark)

    Fagerlund, Birgitte; Pinborg, Lars H; Mortensen, Erik Lykke

    2013-01-01

    Studies of in vivo dopamine receptors in schizophrenia have mostly focused on D2 receptors in striatal areas or on D1 receptors in cortex. No previous study has examined the correlation between cortical dopamine D2/3 receptor binding potentials and cognition in schizophrenia patients. The objecti...

  20. The Sport League's Dilemma : Competitive Balance versus Incentives to Win

    NARCIS (Netherlands)

    Palomino, F.A.; Rigotti, L.

    2000-01-01

    We analyze a dynamic model of strategic interaction between a professional sport league that organizes a tournament, the teams competing to win it, and the broadcasters paying for the rights to televise it.Teams and broadcasters maximize expected profits, while the league's objective may be either

  1. Winning the pressing down game but not Banach Mazur

    OpenAIRE

    Kellner, Jakob; Pauna, Matti; Shelah, Saharon

    2006-01-01

    Let $S$ be the set of those $\\alpha\\in\\omega_2$ that have cofinality $\\omega_1$. It is consistent relative to a measurable that the nonempty player wins the pressing down game of length $\\omega_1$, but not the Banach Mazur game of length $\\omega+1$ (both games starting with $S$).

  2. Winning Strategies: A Case Study of Oyo State Lottery, Nigeria

    African Journals Online (AJOL)

    PROF. OLIVER OSUAGWA

    2014-06-01

    Jun 1, 2014 ... 3.1 Simulation of Lottery Strategies. The data used for this research work consisted of the year 2011 lottery winning numbers of the Daily draw type of game as collected from the Oyo State Lottery. Commission. The data was used to simulate the random, low frequency and high frequency game strategies.

  3. Tight Focus on Instruction Wins Texas District Prize

    Science.gov (United States)

    Maxwell, Lesli A.

    2009-01-01

    It took a while for four-time finalist Aldine, Texas, to win the Broad Prize for Urban Education. But it took even longer to craft the system that ultimately put the district over the top. Educators in Aldine district have been working for more than a decade to refine their "managed instruction" system. Reviewers examined how the school…

  4. In the winning mood: Affect in the Iowa gambling task

    NARCIS (Netherlands)

    Vries, M. de; Holland, R.W.; Witteman, C.L.M.

    2008-01-01

    The present research aimed to test the role of mood in the Iowa Gambling Task (IGT; Bechara et al., 1994). In the IGT, participants can win or lose money by picking cards from four different decks. They have to learn by experience that two decks are overall advantageous and two decks are overall

  5. Interior design students win two IDEC Student Design Competition awards

    OpenAIRE

    Watson-Bloch, Cathy

    2005-01-01

    Interior Design students in the School of Architecture + Design at Virginia Tech won two of the four awards presented in the 2004-2005 Interior Design Educators Council (IDEC) Student Design Competition. Winners were selected at the International IDEC Conference in Savannah, Ga. with Virginia Tech Interior Design students winning second place and honorable mention.

  6. Are we winning? Improving perinatal outcomes at a deeply rural ...

    African Journals Online (AJOL)

    Are we winning? Improving perinatal outcomes at a deeply rural district hospital in South Africa. CB Gaunt. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.7196/SAMJ.3699 · AJOL African Journals Online. HOW TO ...

  7. Winning in straight sets helps in Grand Slam tennis

    NARCIS (Netherlands)

    Goossens, Dries R.; Kempeneers, Jurgen; Koning, Ruud H.; Spieksma, Frits C. R.

    2015-01-01

    In this contribution, we study whether fatigue resulting from the previous match affects a player's chances of winning his (or her) next match in Grand Slum tennis. We measure relative fatigue levels of two opponents by looking at the difference in number of sets played in their previous match. We

  8. WinDAM C earthen embankment internal erosion analysis software

    Science.gov (United States)

    Two primary causes of dam failure are overtopping and internal erosion. For the purpose of evaluating dam safety for existing earthen embankment dams and proposed earthen embankment dams, Windows Dam Analysis Modules C (WinDAM C) software will simulate either internal erosion or erosion resulting f...

  9. Abstinence and Relapse Rates Following a College Campus-Based Quit & Win Contest

    Science.gov (United States)

    Thomas, Janet L.; An, Larry; Luo, Xianghua; Scherber, Robyn M.; Berg, Carla J.; Golden, Dave; Ehlinger, Edward P.; Murphy, Sharon E.; Hecht, Stephen S.; Ahluwalia, Jasjit S.

    2010-01-01

    Objective: To conduct and evaluate Quit & Win contests at 2 2-year college and 2 4-year university campuses. Participants: During Spring semester, 2006, undergraduates (N = 588) interested in quitting smoking signed up for a Quit & Win 30-day cessation contest for a chance to win a lottery prize. Methods: Participants (N = 588) completed a…

  10. Windows Calorimeter Control (WinCal) program computer software design description

    International Nuclear Information System (INIS)

    Pertzborn, N.F.

    1997-01-01

    The Windows Calorimeter Control (WinCal) Program System Design Description contains a discussion of the design details for the WinCal product. Information in this document will assist a developer in maintaining the WinCal system. The content of this document follows the guidance in WHC-CM-3-10, Software Engineering Standards, Standard for Software User Documentation

  11. The effects of donor stage on the survival and function of embryonic striatal grafts in the adult rat brain; II. Correlation between positron emission tomography and reaching behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Dunnett, S.B. [Department of Experimental Psychology and MRC Cambridge Centre for Brain Repair, University of Cambridge, Cambridge (United Kingdom); Brooks, D.J.; Ashworth, S.; Opacka-Juffrey, J.; Myers, R.; Hume, S.P. [PET Methodology Group, Cyclotron Unit, MRC Clinical Science Centre, Hammersmith Hospital, London (United Kingdom); Torres, E.M.; Fricker, R.A. [Department of Experimental Psychology and MRC Cambridge Centre for Brain Repair, University of Cambridge, Cambridge (United Kingdom)

    1997-05-26

    Grafts of embryonic striatal primordia are able to elicit behavioural recovery in rats which have received an excitotoxic lesion to the striatum, and it is believed that the P zones or striatal-like tissue within the transplants play a crucial role in these functional effects. We performed this study to compare the effects of different donor stage of embryonic tissue on both the morphology (see accompanying paper) and function of striatal transplants. Both the medial and lateral ganglionic eminence was dissected from rat embryos of either 10 mm, 15 mm, 19 mm, or 23 mm crown-rump length, and implanted as a cell suspension into adult rats which had received an ibotenic acid lesion 10 days prior to transplantation. After four months the animals were tested on the 'staircase task' of skilled forelimb use. At 10-14 months rats from the groups which had received grafts from 10 mm or 15 mm donor embryos were taken for positron emission tomography scanning in a small diameter postiron emission tomography scanner, using ligands to the dopamine D{sub 1} and D{sub 2} receptors, [{sup 11}C]SCH 23390 and [{sup 11}C]raclopride, respectively. A lesion-alone group was also scanned with the same ligands for comparison. Animals which had received transplants from the 10 mm donors showed a significant recovery with their contralateral paw on the 'staircase test'. No other groups showed recovery on this task. Similarly, the animals with grafts from the youngest donors showed a significant increase in D{sub 1} and D{sub 2} receptor binding when compared to the lesion-alone group. No increase in signal was observed with either ligand in the group which had received grafts from 15 mm donors. Success in paw reaching showed a strong correlation to both the positron emission tomography signal obtained and the P zone volume of the grafts.These results suggest that striatal grafts from younger donors (10 mm CRL) give greater behavioural recovery than grafts preparedfrom

  12. Striatal and extra-striatal dopamine transporter in cannabis and tobacco addiction: a high resolution PET study

    International Nuclear Information System (INIS)

    Leroy, C.; Martinot, J.L.; Duchesnay, E.; Artiges, E.; Ribeiro, M.J.; Trichard, Ch.; Karila, L.; Lukasiewicz, M.; Benyamina, A.; Reynaud, M.; Martinot, J.L.; Duchesnay, E.; Artiges, E.; Comtat, C.; Artiges, E.; Trichard, Ch.

    2011-01-01

    The dopamine (DA) system is known to be involved in the reward and dependence mechanisms of addiction. However, modifications in dopaminergic neurotransmission associated with long-term tobacco and cannabis use have been poorly documented in vivo. In order to assess striatal and extra-striatal dopamine transporter (DAT) availability in tobacco and cannabis addiction, three groups of male age-matched subjects were compared: 11 healthy non-smoker subjects, 14 tobacco-dependent smokers (17.6 ± 5.3 cigarettes/day for 12.1 ± 8.5 years) and 13 cannabis and tobacco smokers (CTS) (4.8 ± 5.3 cannabis joints/day for 8.7 ± 3.9 years). DAT availability was examined in positron emission tomography (HRRT) with a high resolution research tomograph after injection of [ 11 C]PE2I, a selective DAT radioligand. Region of interest and voxel-by-voxel approaches using a simplified reference tissue model were performed for the between-group comparison of DAT availability. Measurements in the dorsal striatum from both analyses were concordant and showed a mean 20% lower DAT availability in drug users compared with controls. Whole-brain analysis also revealed lower DAT availability in the ventral striatum, the midbrain, the middle cingulate and the thalamus (ranging from -15 to -30%). The DAT availability was slightly lower in all regions in CTS than in subjects who smoke tobacco only, but the difference does not reach a significant level. These results support the existence of a decrease in DAT availability associated with tobacco and cannabis addictions involving all dopaminergic brain circuits. These findings are consistent with the idea of a global decrease in cerebral DA activity in dependent subjects. (authors)

  13. Cortico-Striatal Spike-Timing Dependent Plasticity After Activation of Subcortical Pathways

    OpenAIRE

    Schulz, Jan M.; Redgrave, Peter; Reynolds, John N. J.

    2010-01-01

    Cortico-striatal spike-timing dependent plasticity (STDP) is modulated by dopamine in vitro. The present study investigated STDP in vivo using alternative procedures for modulating dopaminergic inputs. Postsynaptic potentials (PSP) were evoked in intracellularly recorded spiny neurons by electrical stimulation of the contralateral motor cortex. PSPs often consisted of up to three distinct components, likely representing distinct cortico-striatal pathways. After baseline recording, bicucullin...

  14. A negative relationship between ventral striatal loss anticipation response and impulsivity in borderline personality disorder

    OpenAIRE

    Herbort, Maike C.; Soch, Joram; W?stenberg, Torsten; Krauel, Kerstin; Pujara, Maia; Koenigs, Michael; Gallinat, J?rgen; Walter, Henrik; Roepke, Stefan; Schott, Bj?rn H.

    2016-01-01

    Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BP...

  15. Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

    OpenAIRE

    Wiltschko, Alexander B; Pettibone, Jeffrey R; Berke, Joshua D

    2010-01-01

    Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by di...

  16. Corticostriatal interactions in the generation of tic-like behaviors after local striatal disinhibition

    Science.gov (United States)

    Pogorelov, Vladimir; Xu, Meiyu; Smith, Haleigh R.; Buchanan, Gordon F.; Pittenger, Christopher

    2015-01-01

    The pathophysiology of the tics that define Gilles de la Tourette syndrome (TS) is not well understood. Local disinhibition within the striatum has been hypothesized to play a pathogenic role. In support of this, experimental disinhibition by local antagonism of GABA-A receptors within the striatum produces tic-like phenomenology in monkey and rat. We replicated this effect in mice via local picrotoxin infusion into the dorsal striatum. Infusion of picrotoxin into sensorimotor cortex produced similar movements, accompanied by signs of behavioral activation; higher-dose picrotoxin in the cortex produced seizures. Striatal inhibition with local muscimol completely abolished tic-like movements after either striatal or cortical picrotoxin, confirming their dependence on the striatal circuitry; in contrast, cortical muscimol attenuated but did not abolish movements produced by striatal picrotoxin. Striatal glutamate blockade eliminated tic-like movements after striatal picrotoxin, indicating that glutamatergic afferents are critical for their generation. These studies replicate and extend previous work in monkey and rat, providing additional validation for the local disinhibition model of tic generation. Our results reveal a key role for corticostriatal glutamatergic afferents in the generation of tic-like movements in this model. PMID:25597650

  17. Serial imaging of bilateral striatal necrosis associated with acidaemia in adults

    International Nuclear Information System (INIS)

    Kamei, S.; Takasu, T.; Mori, N.; Yoshihashi, K.; Shikata, E.

    1996-01-01

    Bilateral striatal necrosis in acute encephalopathy has been reported in a small number of adults with methanol or cyanide intoxication, hypoxic encephalopathy or haemolytic-uraemic syndrome. Acute encephalopathy with bilateral striatal necrosis has been reported in infants and children. However, the pathogenesis of the necrosis remains unclear. This is the first report of serial imaging from the very early yo chronic stage in two acute encephalopathic adults with bilateral striatal necrosis. A clinicoradiological study is presented for clarification of the pathological process and pathogenesis. Striatal lesions were not detected in the very early stages, but only thereafter. Serial studies suggested that the lesions were caused by delayed neuronal death. These patients had severe lactic acidosis, near the limit for survival. There hav ebeen few reports of adults with acute encephalopathy and bilateral striatal necrosis in whom arterial pH was described; all these exhibited marked acidosis. The common pathophysiological condition among these encephalopathies with bilateral striatal necrosis could be lactic acidosis elicited by impairnment of ATP generation through the Krebs cycle. The striatum might represent one of the target areas of Krebs-cycle blockade. (orig.)

  18. Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats.

    Science.gov (United States)

    Der-Avakian, Andre; D'Souza, Manoranjan S; Potter, David N; Chartoff, Elena H; Carlezon, William A; Pizzagalli, Diego A; Markou, Athina

    2017-05-01

    Mood disorders can be triggered by stress and are characterized by deficits in reward processing, including disrupted reward learning (the ability to modulate behavior according to past rewards). Reward learning is regulated by the anterior cingulate cortex (ACC) and striatal circuits, both of which are implicated in the pathophysiology of mood disorders. Here, we assessed in rats the effects of a potent stressor (social defeat) on reward learning and gene expression in the ACC, ventral tegmental area (VTA), and striatum. Adult male Wistar rats were trained on an operant probabilistic reward task (PRT) and then exposed to 3 days of social defeat before assessment of reward learning. After testing, the ACC, VTA, and striatum were dissected, and expression of genes previously implicated in stress was assessed. Social defeat blunted reward learning (manifested as reduced response bias toward a more frequently rewarded stimulus) and was associated with increased nociceptin/orphanin FQ (N/OFQ) peptide mRNA levels in the striatum and decreased Fos mRNA levels in the VTA. Moreover, N/OFQ peptide and nociceptin receptor mRNA levels in the ACC, VTA and striatum were inversely related to reward learning. The behavioral findings parallel previous data in humans, suggesting that stress similarly disrupts reward learning in both species. Increased striatal N/OFQ mRNA in stressed rats characterized by impaired reward learning is consistent with accumulating evidence that antagonism of nociceptin receptors, which bind N/OFQ, has antidepressant-like effects. These results raise the possibility that nociceptin systems represent a molecular substrate through which stress produces reward learning deficits in mood disorders.

  19. PD 102807, a novel muscarinic M4 receptor antagonist, discriminates between striatal and cortical muscarinic receptors coupled to cyclic AMP.

    Science.gov (United States)

    Olianas, M C; Onali, P

    1999-01-01

    In membranes of Chinese hamster ovary cells expressing the cloned human M1-M4 muscarinic receptor subtypes, PD 102807, a novel M4 selective antagonist, was found to counteract the M4 receptor-induced stimulation of [35S]-GTPgammaS binding to membrane G proteins with a pK(B) of 7.40, a value which was 63-, 33- and 10-fold higher than those displayed at M1 (pK(B) = 5.60), M2 (pK(B) = 5.88) and M3 (pK(B) = 6.39) receptor subtypes, respectively. In rat striatal membranes, PD 102807 antagonized the muscarinic inhibition of dopamine (DA) D1 receptor-stimulated adenylyl cyclase with a pK(B) value of 7.36. In contrast, in membranes of rat frontal cortex, PD 102807 displayed lower potencies in antagonizing either the muscarinic facilitation of corticotropin releasing hormone (CRH)-stimulated adenylyl cyclase (pK(B) = 5.79) or inhibition of Ca2+/calmodulin (Ca2+/CaM)-stimulated enzyme activity (pK(B) = 5.95). In each response investigated, PD 102807 interacted with muscarinic receptors in a manner typical of a simple competitive antagonist. These data provide additional evidence that PD 102807 is a M4-receptor preferring antagonist and that this compound can discriminate the striatal muscarinic receptors inhibiting DA D1 receptor activity from the cortical receptors mediating the potentiation of CRH receptor signalling and the inhibition of Ca2+/CaM-stimulated adenylyl cyclase activity.

  20. New Repeat Polymorphism in theAKT1Gene Predicts Striatal Dopamine D2/D3 Receptor Availability and Stimulant-Induced Dopamine Release in the Healthy Human Brain.

    Science.gov (United States)

    Shumay, Elena; Wiers, Corinde E; Shokri-Kojori, Ehsan; Kim, Sung Won; Hodgkinson, Colin A; Sun, Hui; Tomasi, Dardo; Wong, Christopher T; Weinberger, Daniel R; Wang, Gene-Jack; Fowler, Joanna S; Volkow, Nora D

    2017-05-10

    The role of the protein kinase Akt1 in dopamine neurotransmission is well recognized and has been implicated in schizophrenia and psychosis. However, the extent to which variants in the AKT1 gene influence dopamine neurotransmission is not well understood. Here we investigated the effect of a newly characterized variant number tandem repeat (VNTR) polymorphism in AKT1 [major alleles: L- (eight repeats) and H- (nine repeats)] on striatal dopamine D2/D3 receptor (DRD2) availability and on dopamine release in healthy volunteers. We used PET and [ 11 C]raclopride to assess baseline DRD2 availability in 91 participants. In 54 of these participants, we also measured intravenous methylphenidate-induced dopamine release to measure dopamine release. Dopamine release was quantified as the difference in specific binding of [ 11 C]raclopride (nondisplaceable binding potential) between baseline values and values following methylphenidate injection. There was an effect of AKT1 genotype on DRD2 availability at baseline for the caudate ( F (2,90) = 8.2, p = 0.001) and putamen ( F (2,90) = 6.6, p = 0.002), but not the ventral striatum ( p = 0.3). For the caudate and putamen, LL showed higher DRD2 availability than HH; HL were in between. There was also a significant effect of AKT1 genotype on dopamine increases in the ventral striatum ( F (2,53) = 5.3, p = 0.009), with increases being stronger in HH > HL > LL. However, no dopamine increases were observed in the caudate ( p = 0.1) or putamen ( p = 0.8) following methylphenidate injection. Our results provide evidence that the AKT1 gene modulates both striatal DRD2 availability and dopamine release in the human brain, which could account for its association with schizophrenia and psychosis. The clinical relevance of the newly characterized AKT1 VNTR merits investigation. SIGNIFICANCE STATEMENT The AKT1 gene has been implicated in schizophrenia and psychosis. This association is likely to reflect modulation of dopamine signaling by

  1. Formats of Winning Strategies for Six Types of Pushdown Games

    Directory of Open Access Journals (Sweden)

    Wladimir Fridman

    2010-06-01

    Full Text Available The solution of parity games over pushdown graphs (Walukiewicz '96 was the first step towards an effective theory of infinite-state games. It was shown that winning strategies for pushdown games can be implemented again as pushdown automata. We continue this study and investigate the connection between game presentations and winning strategies in altogether six cases of game arenas, among them realtime pushdown systems, visibly pushdown systems, and counter systems. In four cases we show by a uniform proof method that we obtain strategies implementable by the same type of pushdown machine as given in the game arena. We prove that for the two remaining cases this correspondence fails. In the conclusion we address the question of an abstract criterion that explains the results.

  2. Monetary discounting and ventral striatal dopamine receptor availability in nontreatment-seeking alcoholics and social drinkers.

    Science.gov (United States)

    Oberlin, Brandon G; Albrecht, Daniel S; Herring, Christine M; Walters, James W; Hile, Karen L; Kareken, David A; Yoder, Karmen K

    2015-06-01

    Dopamine (DA) in the ventral striatum (VST) has long been implicated in addiction pathologies, yet its role in temporal decision-making is not well-understood. To determine if VST DA D2 receptor availability corresponds with greater impulsive choice in both nontreatment-seeking alcoholics (NTS) and social drinkers (SD). NTS subjects (n = 10) and SD (n = 13) received PET scans at baseline with the D2/D3 radioligand [(11)C]raclopride (RAC). Outside the scanner, subjects performed a delay discounting procedure with monetary rewards. RAC binding potential (BPND) was estimated voxelwise, and correlations were performed to test for relationships between VST BPND and delay discounting performance. Self-reported impulsivity was also tested for correlations with BPND. Across all subjects, greater impulsive choice for $20 correlated with lower BPND in the right VST. NTS showed greater impulsive choice than SD and were more impulsive by self-report. Across all subjects, the capacity of larger rewards to reduce impulsive choice (the magnitude effect) correlated negatively (p = 0.028) with problematic alcohol use (AUDIT) scores. Self-reported impulsivity did not correlate with BPND in VST. Preference for immediate reinforcement may reflect greater endogenous striatal DA or lower D2 number, or both. Alcoholic status did not mediate significant effects on VST BPND, suggesting minimal effects from alcohol exposure. The apparent lack of BPND correlation with self-reported impulsivity highlights the need for objective behavioral assays in the study of the neurochemical substrates of behavior. Finally, our results suggest that the magnitude effect may be more sensitive to alcohol-induced problems than single discounting measures.

  3. [Development of a Striatal and Skull Phantom for Quantitative123I-FP-CIT SPECT].

    Science.gov (United States)

    Ishiguro, Masanobu; Uno, Masaki; Miyazaki, Takuma; Kataoka, Yumi; Toyama, Hiroshi; Ichihara, Takashi

    2018-01-01

    123 Iodine-labelled N-(3-fluoropropyl) -2β-carbomethoxy-3β-(4-iodophenyl) nortropane ( 123 I-FP-CIT) single photon emission computerized tomography (SPECT) images are used for differential diagnosis such as Parkinson's disease (PD). Specific binding ratio (SBR) is affected by scattering and attenuation in SPECT imaging, because gender and age lead to changes in skull density. It is necessary to clarify and correct the influence of the phantom simulating the the skull. The purpose of this study was to develop phantoms that can evaluate scattering and attenuation correction. Skull phantoms were prepared based on the measuring the results of the average computed tomography (CT) value, average skull thickness of 12 males and 16 females. 123 I-FP-CIT SPECT imaging of striatal phantom was performed with these skull phantoms, which reproduced normal and PD. SPECT images, were reconstructed with scattering and attenuation correction. SBR with partial volume effect corrected (SBR act ) and conventional SBR (SBR Bolt ) were measured and compared. The striatum and the skull phantoms along with 123 I-FP-CIT were able to reproduce the normal accumulation and disease state of PD and further those reproduced the influence of skull density on SPECT imaging. The error rate with the true SBR, SBR act was much smaller than SBR Bolt . The effect on SBR could be corrected by scattering and attenuation correction even if the skull density changes with 123 I-FP-CIT on SPECT imaging. The combination of triple energy window method and CT-attenuation correction method would be the best correction method for SBR act .

  4. Striatal dopamine release and genetic variation of the serotonin 2C receptor in humans.

    Science.gov (United States)

    Mickey, Brian J; Sanford, Benjamin J; Love, Tiffany M; Shen, Pei-Hong; Hodgkinson, Colin A; Stohler, Christian S; Goldman, David; Zubieta, Jon-Kar

    2012-07-04

    Mesoaccumbal and nigrostriatal projections are sensitive to stress, and heightened stress sensitivity is thought to confer risk for neuropsychiatric disorders. Serotonin 2C (5-HT(2C)) receptors mediate the inhibitory effects of serotonin on dopaminergic circuitry in experimental animals, and preclinical findings have implicated 5-HT(2C) receptors in motivated behaviors and psychotropic drug mechanisms. In humans, a common missense single-nucleotide change (rs6318, Cys23Ser) in the 5-HT(2C) receptor gene (HTR2C) has been associated with altered activity in vitro and with clinical mood disorders. We hypothesized that dopaminergic circuitry would be more sensitive to stress in humans carrying the Ser23 variant. To test this hypothesis, we studied 54 healthy humans using positron emission tomography and the displaceable D(2)/D(3) receptor radiotracer [(11)C]raclopride. Binding potential (BP(ND)) was quantified before and after a standardized stress challenge consisting of 20 min of moderate deep muscular pain, and reduction in BP(ND) served as an index of dopamine release. The Cys23Ser variant was genotyped on a custom array, and ancestry informative markers were used to control for population stratification. We found greater dopamine release in the nucleus accumbens, caudate nucleus, and putamen among Ser23 carriers, after controlling for sex, age, and ancestry. Genotype accounted for 12% of the variance in dopamine release in the nucleus accumbens. There was no association of Cys23Ser with baseline BP(ND). These findings indicate that a putatively functional HTR2C variant (Ser23) is associated with greater striatal dopamine release during pain in healthy humans. Mesoaccumbal stress sensitivity may mediate the effects of HTR2C variation on risk of neuropsychiatric disorders.

  5. Western Diet Chow Consumption in Rats Induces Striatal Neuronal Activation While Reducing Dopamine Levels without Affecting Spatial Memory in the Radial Arm Maze.

    Science.gov (United States)

    Nguyen, Jason C D; Ali, Saher F; Kosari, Sepideh; Woodman, Owen L; Spencer, Sarah J; Killcross, A Simon; Jenkins, Trisha A

    2017-01-01

    Rats fed high fat diets have been shown to be impaired in hippocampal-dependent behavioral tasks, such as spatial recognition in the Y-maze and reference memory in the Morris water maze (MWM). It is clear from previous studies, however, that motivation and reward factor into the memory deficits associated with obesity and high-fat diet consumption, and that the prefrontal cortex and striatum and neurotransmitter dopamine play important roles in cognitive performance. In this series of studies we extend our research to investigate the effect of a high fat diet on striatal neurochemistry and performance in the delayed spatial win-shift radial arm maze task, a paradigm highly reliant on dopamine-rich brain regions, such as the striatum after high fat diet consumption. Memory performance, neuronal activation and brain dopaminergic levels were compared in rats fed a "Western" (21% fat, 0.15% cholesterol) chow diet compared to normal diet (6% fat, 0.15% cholesterol)-fed controls. Twelve weeks of dietary manipulation produced an increase in weight in western diet-fed rats, but did not affect learning and performance in the delayed spatial win-shift radial arm maze task. Concurrently, there was an observed decrease in dopamine levels in the striatum and a reduction of dopamine turnover in the hippocampus in western diet-fed rats. In a separate cohort of rats Fos levels were measured after rats had been placed in a novel arena and allowed to explore freely. In normal rats, this exposure to a unique environment did not affect neuronal activation. In contrast, rats fed a western diet were found to have significantly increased Fos expression in the striatum, but not prefrontal cortex or hippocampus. Our study demonstrates that while western diet consumption in rats produces weight gain and brain neuronal and neurotransmitter changes, it did not affect performance in the delayed spatial win-shift paradigm in the radial arm maze. We conclude that modeling the cognitive decline

  6. Optimizing Distribution Problems using WinQSB Software

    Directory of Open Access Journals (Sweden)

    Daniel Mihai Amariei

    2015-07-01

    Full Text Available In the present paper we are presenting a problem of distribution using the Network Modeling Module of the WinQSB software, were we have 5 athletes which we must assign the optimal sample, function of the obtained time, so as to obtain the maximum output of the athletes. Also we analyzed the case of an accident of 2 athletes, the coupling of 3 athletes with 5 various athletic events causing the maximum coupling, done using the Hungarian algorithm.

  7. Insurgent Safe Havens: Can We Win the Fight?

    Science.gov (United States)

    2011-03-08

    factory, a clothing factory, an arms factory, a ~ bakery , hospitals, possible a radio transmitter, a printing press, etc." 17 Che viewed sanctuary as...to beat and proved that an inferior force when properly hidden, striking the weak points of the enemy at the time and place of their choosing can...Record, Jeffery, Beating Goliath, Why Insurgencies Win, (Washington, DC: Potomac Books Inc.). Pg X 5 Clausewitz, Carl Von, On War, Edited by Michael

  8. An elementary introduction to Bayesian computing using WinBUGS.

    Science.gov (United States)

    Fryback, D G; Stout, N K; Rosenberg, M A

    2001-01-01

    Bayesian statistics provides effective techniques for analyzing data and translating the results to inform decision making. This paper provides an elementary tutorial overview of the WinBUGS software for performing Bayesian statistical analysis. Background information on the computational methods used by the software is provided. Two examples drawn from the field of medical decision making are presented to illustrate the features and functionality of the software.

  9. Arming USAF Senior Leaders With Words To Win

    Science.gov (United States)

    2016-03-01

    AU/ACSC/CORBIN, R/AY16 2 AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY ARMING USAF SENIOR LEADERS WITH WORDS TO WIN by...this toolset for leaders (or its viable utility as an option for implementation) this research looks at the current training provided to both senior ...accurately, as well as the current training provided to both senior leaders in the USAF and to the personnel that support them in their communication

  10. Free radical production induced by methamphetamine in rat striatal synaptosomes.

    Science.gov (United States)

    Pubill, David; Chipana, Carlos; Camins, Antonio; Pallàs, Mercè; Camarasa, Jordi; Escubedo, Elena

    2005-04-01

    The pro-oxidative effect of methamphetamine (METH) in dopamine terminals was studied in rat striatal synaptosomes. Flow cytometry analysis showed increased production of reactive oxygen species (ROS) in METH-treated synaptosomes, without reduction in the density of dopamine transporters. In synaptosomes from dopamine (DA)-depleted animals, METH did not induce ROS production. Reserpine, in vitro, completely inhibited METH-induced ROS production. These results point to endogenous DA as the main source of ROS induced by METH. Antioxidants and inhibitors of neuronal nitric oxide synthase and protein kinase C (PKC) prevented the METH-induced oxidative effect. EGTA and the specific antagonist methyllycaconitine (MLA, 50 microM) prevented METH-induced ROS production, thus implicating calcium and alpha7 nicotinic receptors in such effect. Higher concentrations of MLA (>100 microM) showed nonspecific antioxidant effect. Preincubation of synaptosomes with METH (1 microM) for 30 min reduced [(3)H]DA uptake by 0%. The METH effect was attenuated by MLA and EGTA and potentiated by nicotine, indicating that activation of alpha(7) nicotinic receptors and Ca(2+) entry are necessary and take place before DAT inhibition. From these findings, it can be postulated that, in our model, METH induces DA release from synaptic vesicles to the cytosol. Simultaneously, METH activates alpha(7) nicotinic receptors, probably inducing depolarization and an increase in intrasynaptosomal Ca(2+). This would lead to DAT inhibition and NOS and PKC activation, initiating oxidation of cytosolic DA.

  11. Reduced Striatal Dopamine Transporters in People with Internet Addiction Disorder

    Directory of Open Access Journals (Sweden)

    Haifeng Hou

    2012-01-01

    Full Text Available In recent years, internet addiction disorder (IAD has become more prevalent worldwide and the recognition of its devastating impact on the users and society has rapidly increased. However, the neurobiological mechanism of IAD has not bee fully expressed. The present study was designed to determine if the striatal dopamine transporter (DAT levels measured by T99mc-TRODAT-1 single photon emission computed tomography (SPECT brain scans were altered in individuals with IAD. SPECT brain scans were acquired on 5 male IAD subjects and 9 healthy age-matched controls. The volume (V and weight (W of bilateral corpus striatum as well as the T99mc-TRODAT-1 uptake ratio of corpus striatum/the whole brain (Ra were calculated using mathematical models. It was displayed that DAT expression level of striatum was significantly decreased and the V, W, and Ra were greatly reduced in the individuals with IAD compared to controls. Taken together, these results suggest that IAD may cause serious damages to the brain and the neuroimaging findings further illustrate IAD is associated with dysfunctions in the dopaminergic brain systems. Our findings also support the claim that IAD may share similar neurobiological abnormalities with other addictive disorders.

  12. Frontal and striatal alterations associated with psychopathic traits in adolescents

    Science.gov (United States)

    Yang, Yaling; Narr, Katherine L.; Baker, Laura A.; Joshi, Shantanu H.; Jahanshad, Neda; Raine, Adrian; Thompson, Paul M.

    2016-01-01

    Neuroimaging research has demonstrated a range of structural deficits in adults with psychopathy, but little is known about structural correlates of psychopathic tendencies in adolescents. Here we examined structural magnetic resonance imaging (sMRI) data obtained from 14-year-old adolescents (n=108) using tensor-based morphometry (TBM) to isolate global and localized differences in brain tissue volumes associated with psychopathic traits in this otherwise healthy developmental population. We found that greater levels of psychopathic traits were correlated with increased brain tissue volumes in the left putamen, left ansa peduncularis, right superiomedial prefrontal cortex, left inferior frontal cortex, right orbitofrontal cortex, and right medial temporal regions and reduced brain tissues volumes in the right middle frontal cortex, left superior parietal lobule, and left inferior parietal lobule. Post hoc analyses of parcellated regional volumes also showed putamen enlargements to correlate with increased psychopathic traits. Consistent with earlier studies, findings suggest poor decision-making and emotional dysregulation associated with psychopathy may be due, in part, to structural anomalies in frontal and temporal regions whereas striatal structural variations may contribute to sensation-seeking and reward-driven behavior in psychopathic individuals. Future studies will help clarify how disturbances in brain maturational processes might lead to the developmental trajectory from psychopathic tendencies in adolescents to adult psychopathy. PMID:25676553

  13. Doubling Your Payoff: Winning Pain Relief Engages Endogenous Pain Inhibition

    Science.gov (United States)

    Becker, Susanne; Gandhi, Wiebke; Kwan, Saskia; Ahmed, Alysha-Karima; Schweinhardt, Petra

    2015-01-01

    When in pain, pain relief is much sought after, particularly for individuals with chronic pain. In analogy to augmentation of the hedonic experience ("liking") of a reward by the motivation to obtain a reward ("wanting"), the seeking of pain relief in a motivated state might increase the experience of pain relief when obtained. We tested this hypothesis in a psychophysical experiment in healthy human subjects, by assessing potential pain-inhibitory effects of pain relief "won" in a wheel of fortune game compared with pain relief without winning, exploiting the fact that the mere chance of winning induces a motivated state. The results show pain-inhibitory effects of pain relief obtained by winning in behaviorally assessed pain perception and ratings of pain intensity. Further, the higher participants scored on the personality trait novelty seeking, the more pain inhibition was induced. These results provide evidence that pain relief, when obtained in a motivated state, engages endogenous pain-inhibitory systems beyond the pain reduction that underlies the relief in the first place. Consequently, such pain relief might be used to improve behavioral pain therapy, inducing a positive, perhaps self-amplifying feedback loop of reduced pain and improved functionality.

  14. Ascorbic acid and striatal transport of [3H]1-methyl-4-phenylpyridine (MPP+) and [3H]dopamine

    International Nuclear Information System (INIS)

    Debler, E.A.; Hashim, A.; Lajtha, A.; Sershen, H.

    1988-01-01

    The inhibition of uptake of [ 3 H]dopamine and [ 3 H]1-methyl-4-phenylpyridine (MPP + ) was examined in mouse striatal synaptosomal preparations. Kinetic analysis indicated that ascorbic acid is a noncompetitive inhibitor of [ 3 H]MPP + uptake. No inhibition of [ 3 H]dopamine uptake is observed. The dopamine uptake blockers, GBR-12909, cocaine, and mazindol strongly inhibit (IC 50 3 H]dopamine and [ 3 H]MPP + transport. Nicotine, its metabolites, and other tobacco alkaloids are weak inhibitors except 4-phenylpyridine and lobeline, which are moderate inhibitors of both [ 3 H]dopamine and [ 3 H]MPP + uptake. These similarities in potencies are in agreement with the suggestion that [ 3 H]MPP + and [ 3 H] are transported by the same carrier. The differences observed in the alteration of dopaminergic transport and mazindol binding by ascorbic acid suggest that ascorbic acid's effects on [ 3 H]MPP + transport are related to translocation and/or dissociation processes occurring subsequent to the initial binding event

  15. Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Carmela Giampà

    2010-10-01

    Full Text Available Huntington's disease is a devastating neurodegenerative condition for which there is no therapy to slow disease progression. The particular vulnerability of striatal medium spiny neurons to Huntington's pathology is hypothesized to result from transcriptional dysregulation within the cAMP and CREB signaling cascades in these neurons. To test this hypothesis, and a potential therapeutic approach, we investigated whether inhibition of the striatal-specific cyclic nucleotide phosphodiesterase PDE10A would alleviate neurological deficits and brain pathology in a highly utilized model system, the R6/2 mouse.R6/2 mice were treated with the highly selective PDE10A inhibitor TP-10 from 4 weeks of age until euthanasia. TP-10 treatment significantly reduced and delayed the development of the hind paw clasping response during tail suspension, deficits in rotarod performance, and decrease in locomotor activity in an open field. Treatment prolonged time to loss of righting reflex. These effects of PDE10A inhibition on neurological function were reflected in a significant amelioration in brain pathology, including reduction in striatal and cortical cell loss, the formation of striatal neuronal intranuclear inclusions, and the degree of microglial activation that occurs in response to the mutant huntingtin-induced brain damage. Striatal and cortical levels of phosphorylated CREB and BDNF were significantly elevated.Our findings provide experimental support for targeting the cAMP and CREB signaling pathways and more broadly transcriptional dysregulation as a therapeutic approach to Huntington's disease. It is noteworthy that PDE10A inhibition in the R6/2 mice reduces striatal pathology, consistent with the localization of the enzyme in medium spiny neurons, and also cortical pathology and the formation of neuronal nuclear inclusions. These latter findings suggest that striatal pathology may be a primary driver of these secondary pathological events. More

  16. Substituting sugar confectionery with fruit and healthy snacks at checkout - a win-win strategy for consumers and food stores?

    DEFF Research Database (Denmark)

    Winkler, Lise L.; Christensen, Ulla; Glümer, Charlotte

    2016-01-01

    a 'responsible' branding opportunity for supermarkets, thus representing a win-win strategy for store managers and consumers in the short term. However, the intervention was too modest to draw conclusions on long-term sales and health implications of this initiative. More research is needed to assess whether......BACKGROUND: The widespread use of in-store marketing strategies to induce unhealthy impulsive purchases has implications for shopping experience, food choice and possibly adverse health outcomes. The aim of this study was to examine consumer attitudes and evaluate sales effects of a healthy...... in four stores for 4 weeks. The intervention was evaluated by 48 short exit interviews on consumer perceptions of the intervention and by linear mixed model analyses of supermarket sales data from the intervention area and a matched control area. RESULTS: The qualitative pre-intervention study identified...

  17. A win-win marginal rent analysis for operator and consumer under battery leasing mode in China electric vehicle market

    International Nuclear Information System (INIS)

    Li Zhe; Ouyang Minggao

    2011-01-01

    Recently battery leasing has been introduced into the market by automobile manufacturers and power suppliers due to its potential to reduce the purchase cost of electric vehicles (EVs). However, the profit prospect of battery leasing is still uncertain. This paper takes the views of both the operators and consumers and calculates the 'win-win' marginal rent, which not only ensures the profitability of operators, but also allows consumers a lower expenditure than using Internal combustion engine vehicles (ICVs) and EVs with embedded batteries. Battery cost, vehicle weight, gasoline and electricity price, and the discount rate have impacts on the rent. Battery cost plays a dominant role and a battery cost >5 Yen /W h fails to enable the survival of battery leasing to all types of EVs. Battery leasing would be more competitive when focusing on heavier EVs. At least one of the three thresholds is required for the existence of rent pricing range for a 1000 kg EV: gasoline retail price >6 Yen /L, electricity price <0.6 Yen /kW h, or the discount rate <7%. Typically, the feasible battery rent range is 0.34-0.38 Yen /W h/year for a 1000 kg EV under the present battery cost 2 Yen /W h and China current gasoline and electricity prices. - Highlights: → Rent pricing for EV battery leasing must obey win-win rule for BLO and consumers. → Rent is affected by battery cost, vehicle weight, energy price and discount rate. → Battery cost plays dominant role for the BLO survival as described in '5-3-2' Law. → Heavier EVs are more suitable for battery leasing when battery cost is high. → The profitability of BLO is sensitive to the price of gasoline and electricity.

  18. Is Hosting the Games Enough to Win? A predictive economic model of medal wins at 2014 Winter Olympics

    OpenAIRE

    Wladimir Andreff

    2012-01-01

    An econometric model which has first been estimated on medal wins at Summer Olympics and has predicted 88% of medal distribution at Beijing Games 2008, is revisited for Winter Olympics. After changing some variables to take into account the winter sports specificity, the model is estimated again on all Winter Games since 1964.Then it is used to predict (forecast) the medal distribution per country at the 2014 Sochi Winter Olympics.

  19. Cortico–Amygdala–Striatal Circuits Are Organized as Hierarchical Subsystems through the Primate Amygdala

    Science.gov (United States)

    Cho, Youngsun T.; Ernst, Monique

    2013-01-01

    The prefrontal and insula cortex, amygdala, and striatum are key regions for emotional processing, yet the amygdala's role as an interface between the cortex and striatum is not well understood. In the nonhuman primate (Macaque fascicularis), we analyzed a collection of bidirectional tracer injections in the amygdala to understand how cortical inputs and striatal outputs are organized to form integrated cortico–amygdala–striatal circuits. Overall, diverse prefrontal and insular cortical regions projected to the basal and accessory basal nuclei of the amygdala. In turn, these amygdala regions projected to widespread striatal domains extending well beyond the classic ventral striatum. Analysis of the cases in aggregate revealed a topographic colocalization of cortical inputs and striatal outputs in the amygdala that was additionally distinguished by cortical cytoarchitecture. Specifically, the degree of cortical laminar differentiation of the cortical inputs predicted amygdalostriatal targets, and distinguished three main cortico–amygdala–striatal circuits. These three circuits were categorized as “primitive,” “intermediate,” and “developed,” respectively, to emphasize the relative phylogenetic and ontogenetic features of the cortical inputs. Within the amygdala, these circuits appeared arranged in a pyramidal-like fashion, with the primitive circuit found in all examined subregions, and subsequent circuits hierarchically layered in discrete amygdala subregions. This arrangement suggests a stepwise integration of the functions of these circuits across amygdala subregions, providing a potential mechanism through which internal emotional states are managed with external social and sensory information toward emotionally informed complex behaviors. PMID:23986238

  20. Altered resting state cortico-striatal connectivity in mild to moderate stage Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Youngbin Kwak

    2010-09-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI (fcMRI in mild to moderate stage Parkinson’s patients on and off L-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off L-DOPA compared to controls. This enhanced connectivity was down-regulated by L-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off L-DOPA exhibited increased power in the frequency band 0.02 – 0.05 Hz compared to controls and to PD on L-DOPA. The L-DOPA associated decrease in the power of this frequency range modulated the L-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the L-DOPA associated decrease in power in this frequency band also correlated with the L-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and L-DOPA modulate striatal resting state BOLD signal oscillations and corticostriatal network coherence.

  1. Altered resting-state functional connectivity of striatal-thalamic circuit in bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Shin Teng

    Full Text Available Bipolar disorder is characterized by internally affective fluctuations. The abnormality of inherently mental state can be assessed using resting-state fMRI data without producing task-induced biases. In this study, we hypothesized that the resting-state connectivity related to the frontal, striatal, and thalamic regions, which were associated with mood regulations and cognitive functions, can be altered for bipolar disorder. We used the Pearson's correlation coefficients to estimate functional connectivity followed by the hierarchical modular analysis to categorize the resting-state functional regions of interest (ROIs. The selected functional connectivities associated with the striatal-thalamic circuit and default mode network (DMN were compared between bipolar patients and healthy controls. Significantly decreased connectivity in the striatal-thalamic circuit and between the striatal regions and the middle and posterior cingulate cortex was observed in the bipolar patients. We also observed that the bipolar patients exhibited significantly increased connectivity between the thalamic regions and the parahippocampus. No significant changes of connectivity related to the frontal regions in the DMN were observed. The changed resting-state connectivity related to the striatal-thalamic circuit might be an inherent basis for the altered emotional and cognitive processing in the bipolar patients.

  2. Striatal lesions produce distinctive impairments in reaction time performance in two different operant chambers.

    Science.gov (United States)

    Brasted, P J; Döbrössy, M D; Robbins, T W; Dunnett, S B

    1998-08-01

    The dorsal striatum plays a crucial role in mediating voluntary movement. Excitotoxic striatal lesions in rats have previously been shown to impair the initiation but not the execution of movement in a choice reaction time task in an automated lateralised nose-poke apparatus (the "nine-hole box"). Conversely, when a conceptually similar reaction time task has been applied in a conventional operant chamber (or "Skinner box"), striatal lesions have been seen to impair the execution rather than the initiation of the lateralised movement. The present study was undertaken to compare directly these two results by training the same group of rats to perform a choice reaction time task in the two chambers and then comparing the effects of a unilateral excitotoxic striatal lesion in both chambers in parallel. Particular attention was paid to adopting similar parameters and contingencies in the control of the task in the two test chambers. After striatal lesions, the rats showed predominantly contralateral impairments in both tasks. However, they showed a deficit in reaction time in the nine-hole box but an apparent deficit in response execution in the Skinner box. This finding confirms the previous studies and indicates that differences in outcome are not simply attributable to procedural differences in the lesions, training conditions or tasks parameters. Rather, the pattern of reaction time deficit after striatal lesions depends critically on the apparatus used and the precise response requirements for each task.

  3. Expressing determination: From ENS programme 'Women and nuclear energy' to WIN

    International Nuclear Information System (INIS)

    Heininen-Ojanperae, Marke

    1993-01-01

    WIN is an international association of women working professionally in the fields of nuclear energy and radiation application and willing to devote time to public information. It is established as non-profit making. WIN'S working language is English. WIN aims to contribute to objectively informing the public, especially women, on nuclear energy and radiation, in particular by: meeting regularly to exchange ideas and experiences between countries' WIN information groups, establishing country WIN groups in nuclear countries as widely as practical, supporting each other across borders, working out shared information techniques and information materials for international use. WIN is open to female nuclear and radiation professionals and academics as well as communications specialists, from all over the world, pledged to adhere to the goals of this Charter. The first WINFO Quarterly Newsletter of Women in Nuclear has been published

  4. The Air Campaign vs. Ballistic Missiles: Seeking the Strategic Win in the 21st Century

    Science.gov (United States)

    2017-06-01

    Adapted from the Robert A. Pape, Bombing to Win : Air Power and Coercion in War (Ithaca, NY: Cornell University Press, 1996), 357–58; Eliot...audible 4 Robert A. Pape, Bombing to Win : Air Power and Coercion in War (Ithaca, NY: Cornell University...Cass Series--Studies in Air Power 12. London ; Portland, OR: Frank Cass, 2003. Pape, Robert A. Bombing to Win : Air Power and Coercion in War

  5. Cyberspace Human Capital: Building a Cadre Today to Win Tomorrows War

    Science.gov (United States)

    2016-04-28

    James Kaplan, Naufal Khan and Roger Roberts . Winning the Battle for Technology Talent, Business Technology Office, 2012. 41 Recommendation R8...Building a Cadre Today to Win Tomorrow’s War by Erica Fountain, Brian Viola & Michael Williams, Major United States Air Force A...Schwartz, kick-started the transformation of the USAF’s foundational mission imperatives with a new mission statement: “to fly, fight and win in air

  6. Understanding a Complex World: Why an Emphasis on Empathy Could Better Enable Army Leaders to Win

    Science.gov (United States)

    2016-06-10

    the problem of how to win in a complex world. 1 Brig. Gen. Oscar W. Koch and Robert G. Hayes, G-2: Intelligence for Patton (Atglen, PA: Schiffer...UNDERSTANDING A COMPLEX WORLD: WHY AN EMPHASIS ON EMPATHY COULD BETTER ENABLE ARMY LEADERS TO WIN A thesis presented to the...Leaders to Win 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Matthew J. Fontaine, MAJ 5d. PROJECT NUMBER

  7. Striatal kinetics of ( sup 11 C)-(+)-nomifensine and 6-( sup 18 F)fluoro-L-dopa in Parkinson's disease measured with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Tedroff, J.; Aquilonius, S.-M. (Department of Neurology, University Hospital (Sweden)); Laihinen, A.; Rinne, U. (Department of Neurology, University of Turku (Finland)); Hartvig, P. (Department of Hospital Pharmacy, University Hospital (Sweden)); Anderson, J. (Department of Radiation Sciences, University Hospital (Sweden)); Lundqvist, H. (Svenberg Laboratory, Uppsala University (Sweden)); Haaparanta, M.; Solin, O. (Medical Cyclotron Laboratory, University of Turku (Finland)); Antoni, G.; Gee, A.D.; Ulin, J.; Laangstroem, B. (Department of Organic Chemistry, University Hospital (Sweden))

    1990-01-01

    The kinetics in brain of the dopamine reuptake blocking agent ({sup 11}C)-(+)-nomifensine and the L-dopa analogue 6-({sup 18}F)fluoro-L-dopa were compared in 3 patients with idopathic Parkinson's disease and agematched healthy volunteers using positron emission tomography. Regional uptake was analyzed and quantified according to a 3-compartment model. Retention of both tracers in striatal regions of the parkinsonian patients were reduced compared with the healthy volunteers mainly in the putamen, while the caudate nuclleus was only mildly affected. The reductions were considerably less than the decrease previously reported postmortem for striatal dopamine content in the basal ganglia of patients with Parkinson's disease. A fairly constant ratio between 6-({sup 18}F)fluoro-L-dopa utilization and ({sup 11}C)-(+)-nomifensine binding in the caudate nucleus and the putamen were found in both groups unrelated to the size of the estimated parameters. This indicates that a limiting factor for the utilization of exogenous levodopa in Parkinsons's disease may be a reduced transport capacity for the amino acid into the dopaminergic terminals. (author).

  8. Striatal kinetics of [11C]-(+)-nomifensine and 6-[18F]fluoro-L-dopa in Parkinson's disease measured with positron emission tomography

    International Nuclear Information System (INIS)

    Tedroff, J.; Aquilonius, S.-M.; Laihinen, A.; Rinne, U.; Hartvig, P.; Anderson, J.; Lundqvist, H.; Haaparanta, M.; Solin, O.; Antoni, G.; Gee, A.D.; Ulin, J.; Laangstroem, B.

    1990-01-01

    The kinetics in brain of the dopamine reuptake blocking agent [ 11 C]-(+)-nomifensine and the L-dopa analogue 6-[ 18 F]fluoro-L-dopa were compared in 3 patients with idopathic Parkinson's disease and agematched healthy volunteers using positron emission tomography. Regional uptake was analyzed and quantified according to a 3-compartment model. Retention of both tracers in striatal regions of the parkinsonian patients were reduced compared with the healthy volunteers mainly in the putamen, while the caudate nuclleus was only mildly affected. The reductions were considerably less than the decrease previously reported postmortem for striatal dopamine content in the basal ganglia of patients with Parkinson's disease. A fairly constant ratio between 6-[ 18 F]fluoro-L-dopa utilization and [ 11 C]-(+)-nomifensine binding in the caudate nucleus and the putamen were found in both groups unrelated to the size of the estimated parameters. This indicates that a limiting factor for the utilization of exogenous levodopa in Parkinsons's disease may be a reduced transport capacity for the amino acid into the dopaminergic terminals. (author)

  9. Decreased spontaneous eye blink rates in chronic cannabis users: evidence for striatal cannabinoid-dopamine interactions.

    Directory of Open Access Journals (Sweden)

    Mikael A Kowal

    Full Text Available Chronic cannabis use has been shown to block long-term depression of GABA-glutamate synapses in the striatum, which is likely to reduce the extent to which endogenous cannabinoids modulate GABA- and glutamate-related neuronal activity. The current study aimed at investigating the effect of this process on striatal dopamine levels by studying the spontaneous eye blink rate (EBR, a clinical marker of dopamine level in the striatum. 25 adult regular cannabis users and 25 non-user controls matched for age, gender, race, and IQ were compared. Results show a significant reduction in EBR in chronic users as compared to non-users, suggesting an indirect detrimental effect of chronic cannabis use on striatal dopaminergic functioning. Additionally, EBR correlated negatively with years of cannabis exposure, monthly peak cannabis consumption, and lifetime cannabis consumption, pointing to a relationship between the degree of impairment of striatal dopaminergic transmission and cannabis consumption history.

  10. Key performance indicators for government and non profit agencies: implementing winning KPIs

    National Research Council Canada - National Science Library

    Parmenter, David

    2012-01-01

    "Winning techniques and strategies for nonprofits and government agencies in creating successful and critical key performance indicatorsBy exploring measures that have transformed businesses, David...

  11. Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of SKF38393.

    NARCIS (Netherlands)

    Saigusa, T.; Aono, Y.; Sekino, R.; Uchida, T.; Takada, K.; Oi, Y.; Koshikawa, N.; Cools, A.R.

    2009-01-01

    Like dexamphetamine, SKF38393 induces an increase in striatal dopamine efflux which is insensitive for tetrodotoxin, Ca(2+) independent and prevented by a dopamine transporter inhibitor. The dexamphetamine-induced striatal dopamine efflux originates from both the reserpine-sensitive vesicular

  12. Striatal dopamine in Parkinson disease: A meta-analysis of imaging studies.

    Science.gov (United States)

    Kaasinen, Valtteri; Vahlberg, Tero

    2017-12-01

    A meta-analysis of 142 positron emission tomography and single photon emission computed tomography studies that have investigated striatal presynaptic dopamine function in Parkinson disease (PD) was performed. Subregional estimates of striatal dopamine metabolism are presented. The aromatic L-amino-acid decarboxylase (AADC) defect appears to be consistently smaller than the dopamine transporter and vesicular monoamine transporter 2 defects, suggesting upregulation of AADC function in PD. The correlation between disease severity and dopamine loss appears linear, but the majority of longitudinal studies point to a negative exponential progression pattern of dopamine loss in PD. Ann Neurol 2017;82:873-882. © 2017 American Neurological Association.

  13. Proteostasis in striatal cells and selective neurodegeneration in Huntington’s disease

    Science.gov (United States)

    Margulis, Julia; Finkbeiner, Steven

    2014-01-01

    Selective neuronal loss is a hallmark of neurodegenerative diseases, including Huntington’s disease (HD). Although mutant huntingtin, the protein responsible for HD, is expressed ubiquitously, a subpopulation of neurons in the striatum is the first to succumb. In this review, we examine evidence that protein quality control pathways, including the ubiquitin proteasome system, autophagy, and chaperones, are significantly altered in striatal neurons. These alterations may increase the susceptibility of striatal neurons to mutant huntingtin-mediated toxicity. This novel view of HD pathogenesis has profound therapeutic implications: protein homeostasis pathways in the striatum may be valuable targets for treating HD and other misfolded protein disorders. PMID:25147502

  14. Striatal lesions in delusional parasitosis revealed by magnetic resonance imaging.

    Science.gov (United States)

    Huber, Markus; Karner, Martin; Kirchler, Erwin; Lepping, Peter; Freudenmann, Roland W

    2008-12-12

    Delusional parasitosis (DP) is a syndrome characterized by the firm conviction that small living beings infest the skin. The etiology can be primary and secondary. Structural brain abnormalities in DP have only been reported in case reports often subcortical vascular encephalopathy and right-hemisphere strokes in the temporo-parietal cortex. Systematic brain imaging studies are lacking. We aimed to identify a brain region with structural lesions in patients with DP in order to better understand the pathophysiology of DP. Nine consecutive patients with DP in a psychiatric outpatient department were assessed clinically and by means of cranial magnetic resonance imaging (MRI). Five of the nine cases were diagnosed as having DP as psychotic disorders due to a general medical condition while three had DP arising from pre-existing psychiatric illness and one suffered from a delusional disorder, somatic type (primary form). Four of the five DP cases secondary to a general medical condition (one case could not be analyzed) had striatal lesions predominantly in the putamen. Thalamic or cortical lesions were found in one case, respectively. In the primary DP case and all cases secondary to another psychiatric disorder basal ganglia and subcortical gray matter lesions were absent. In all medical (secondary) DP cases subcortical white matter lesions were found mainly in the centrum semiovale. Three of the five medical DP cases showed severe generalized brain atrophy which was absent in the primary DP case and in the cases secondary to other psychiatric disorders. We present the findings of the first structural MRI study in DP. Our results suggest a possible relevance of structural lesions in the striatum, predominantly the putamen, in the medical (secondary) DP-subgroup. Our findings are in line with other studies demonstrating that the putamen, in addition to its role in motor regulation, represents a brain area that mediates visuo-tactile perception. Disturbed functioning of

  15. Up-regulation of striatal adenosine A2A receptors with iron deficiency in rats. Effects on locomotion and cortico-striatal neurotransmission

    Science.gov (United States)

    Quiroz, César; Pearson, Virginia; Gulyani, Seema; Allen, Richard; Earley, Christopher; Ferré, Sergi

    2010-01-01

    Brain iron deficiency leads to altered dopaminergic function in experimental animals, which can provide a mechanistic explanation for iron deficiency-related human sensory-motor disorders, such as Restless Legs Syndrome (RLS). However, mechanisms linking both conditions have not been determined. Considering the strong modulation exerted by adenosine on dopamine signaling, one connection could involve changes in adenosine receptor expression or function. In the striatum, presynaptic A2A receptors are localized in glutamatergic terminals contacting GABAergic dynorphinergic neurons and their function can be analyzed by the ability of A2A receptor antagonists to block the motor output induced by cortical electrical stimulation. Postsynaptic A2A receptors are localized in the dendritic field of GABAergic enkephalinergic neurons and their function can be analyzed by studying the ability of A2A receptor antagonists to produce locomotor activity and to counteract striatal ERK1/2 phosphorylation induced by cortical electrical stimulation. Increased density of striatal A2A receptors was found in rats fed during three weeks with an iron-deficient diet during the post-weaning period. In iron-deficient rats, the selective A2A receptor antagonist MSX-3, at doses of 1 and 3 mg/kg, was more effective at blocking motor output induced by cortical electrical stimulation (presynaptic A2A receptor-mediated effect) and at enhancing locomotor activation and blocking striatal ERK phosphorylation induced by cortical electrical stimulation (postsynaptic A2A receptor-mediated effects). These results indicate that brain iron deficiency induces a functional up-regulation of both striatal pre- and postsynaptic A2A receptor, which could be involved in sensory-motor disorders associated with iron deficiency such as RLS. PMID:20385128

  16. Up-regulation of striatal adenosine A(2A) receptors with iron deficiency in rats: effects on locomotion and cortico-striatal neurotransmission.

    Science.gov (United States)

    Quiroz, César; Pearson, Virginia; Gulyani, Seema; Allen, Richard; Earley, Christopher; Ferré, Sergi

    2010-07-01

    Brain iron deficiency leads to altered dopaminergic function in experimental animals, which can provide a mechanistic explanation for iron deficiency-related human sensory-motor disorders, such as Restless Legs Syndrome (RLS). However, mechanisms linking both conditions have not been determined. Considering the strong modulation exerted by adenosine on dopamine signaling, one connection could involve changes in adenosine receptor expression or function. In the striatum, presynaptic A(2A) receptors are localized in glutamatergic terminals contacting GABAergic dynorphinergic neurons and their function can be analyzed by the ability of A(2A) receptor antagonists to block the motor output induced by cortical electrical stimulation. Postsynaptic A(2A) receptors are localized in the dendritic field of GABAergic enkephalinergic neurons and their function can be analyzed by studying the ability of A(2A) receptor antagonists to produce locomotor activity and to counteract striatal ERK1/2 phosphorylation induced by cortical electrical stimulation. Increased density of striatal A(2A) receptors was found in rats fed during 3 weeks with an iron-deficient diet during the post-weaning period. In iron-deficient rats, the selective A(2A) receptor antagonist MSX-3, at doses of 1 and 3 mg/kg, was more effective at blocking motor output induced by cortical electrical stimulation (presynaptic A(2A) receptor-mediated effect) and at enhancing locomotor activation and blocking striatal ERK phosphorylation induced by cortical electrical stimulation (postsynaptic A(2A) receptor-mediated effects). These results indicate that brain iron deficiency induces a functional up-regulation of both striatal pre- and postsynaptic A(2A) receptor, which could be involved in sensory-motor disorders associated with iron deficiency such as RLS. Copyright 2010. Published by Elsevier Inc.

  17. [3H]mazindol binding associated with neuronal dopamine and norepinephrine uptake sites.

    Science.gov (United States)

    Javitch, J A; Blaustein, R O; Snyder, S H

    1984-07-01

    [3H]Mazindol labels neuronal dopamine uptake sites in corpus striatum membranes (KD = 18 nM) and neuronal norepinephrine uptake sites in cerebral cortex and submaxillary/sublingual gland membranes (KD = 4 nM). The potencies of various inhibitors of biogenic amine uptake in reducing [3H]mazindol binding in striatal membranes correlate with their potencies for inhibition of neuronal [3H]dopamine accumulation, whereas their potencies in reducing [3H]mazindol binding to cortical and salivary gland membranes correlate with their potencies for inhibition of neuronal [3H]norepinephrine accumulation. Similar to the dopamine and norepinephrine uptake systems, [3H]mazindol binding in all three tissues is dependent upon sodium (with potassium, lithium, rubidium, and Tris being ineffective substitutes) and chloride (with sulfate and phosphate being ineffective substitutes). In membranes of the cerebral cortex and salivary gland, half-maximal stimulation is observed at 50-80 mM NaCl, whereas in membranes of the corpus striatum half-maximal stimulation occurs at 240 mM NaCl. In striatal membranes NaCl increases the affinity of [3H]mazindol binding with no effect on the maximal number of sites. The enhancement of affinity is due to a selective slowing of the dissociation of the ligand from its binding site. The association of [3H]mazindol binding sites with neuronal dopamine uptake sites in the corpus striatum is further supported by the reduction of [3H]mazindol binding sites in striatal membranes following destruction of dopaminergic neurons by 6-hydroxydopamine. Similarly, the association of [3H]mazindol binding sites with neuronal norepinephrine uptake sites in cerebral cortex is supported by the reduction of [3H]mazindol binding to cortical membranes following destruction of noradrenergic neurons by N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine.

  18. Resiliency in American Library Association Award Winning Juvenile Fiction: A Correlational Content Analysis

    Science.gov (United States)

    Foreman, Michelle T.

    2010-01-01

    The purpose of this quantitative content analysis was to determine whether there was a relationship between the age, gender, or race of protagonists in contemporary American Library Association award-winning juvenile literature and the representation of resilience by those characters. Award-winning juvenile fiction and biography books were…

  19. 26 CFR 31.3402(q)-1 - Extension of withholding to certain gambling winnings.

    Science.gov (United States)

    2010-04-01

    ... the statement demanded by each cashier the amount of winnings from identical wagers. Although the... actuarially determined that, on January 3, 1977, D's life expectancy is 5 years. Based on that determination... winning ticket is entitled to proceeds of $100,000 payable either as a lump sum upon demand or $10,000 a...

  20. 26 CFR 1.6011-3 - Requirement of statement from payees of certain gambling winnings.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Requirement of statement from payees of certain gambling winnings. 1.6011-3 Section 1.6011-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... of statement from payees of certain gambling winnings. (a) General rule. Except as provided in...

  1. If Winning Isn't Everything--How Can It Be the Only Thing?

    Science.gov (United States)

    Scherer, Joseph

    1990-01-01

    There is more to a successful school athletic program than a winning record. Winning becomes meaningless when youthful victories subvert personal growth, shallow goals shatter dreams, personality is elevated over principle, and athletics are compromised by economic and social forces. To balance academics and athletics, we must consider our…

  2. 78 FR 52802 - Tin T. Win, M.D., Dismissal of Proceeding

    Science.gov (United States)

    2013-08-26

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Tin T. Win, M.D., Dismissal of Proceeding On... Cause and Immediate Suspension of Registration to Tin T. Win, M.D. (hereinafter, Registrant), of Lake... precludes a finding of mootness, see Robert Charles Ley, 76 FR 20033, 20034 (2011), I directed the...

  3. Advanced Planning and Thorough Documentation--the Basis for Winning Proposals.

    Science.gov (United States)

    Battaglia, Robert A.

    1995-01-01

    States that advanced planning and thorough documentation is required to prepare winning proposals. Shares suggestions for preparing better proposal documentation from the foundation, to the Capture Plan, to the final proposal product--all with a goal of increasing the number of contract wins. (PA)

  4. Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Jilly Naaijen

    2017-01-01

    Conclusion: We found no evidence for glutamatergic neuropathology in TD or ADHD within the fronto-striatal circuits. However, the correlation of OC-symptoms with ACC glutamate concentrations suggests that altered glutamatergic transmission is involved in OC-symptoms within TD, but this needs further investigation.

  5. Agonist-selective effects of opioid receptor ligands on cytosolic calcium concentration in rat striatal neurons.

    Science.gov (United States)

    Brailoiu, G Cristina; Deliu, Elena; Hooper, Robert; Dun, Nae J; Undieh, Ashiwel S; Adler, Martin W; Benamar, Khalid; Brailoiu, Eugen

    2012-06-01

    Buprenorphine is an opioid receptor ligand whose mechanism of action is incompletely understood. Using Ca(2+) imaging, we assessed the effects of buprenorphine, β-endorphin, and morphine on cytosolic Ca(2+) concentration [Ca(2+)](i), in rat striatal neurons. Buprenorphine (0.01-1 μM) increased [Ca(2+)](i) in a dose-dependent manner in a subpopulation of rat striatal neurons. The effect of buprenorphine was largely reduced by naloxone, a non-selective opioid receptor antagonist, but not by μ, κ, δ or NOP-selective antagonists. β-Endorphin (0.1 μM) increased [Ca(2+)](i) with a lower amplitude and slower time course than buprenorphine. Similar to buprenorphine, the effect of β-endorphin was markedly decreased by naloxone, but not by opioid-selective antagonists. Morphine (0.1-10 μM), did not affect [Ca(2+)](i) in striatal neurons. Our results suggest that buprenorphine and β-endorphin act on a distinct type/subtype of plasmalemmal opioid receptors or activate intracellular opioid-like receptor(s) in rat striatal neurons. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson's disease.

    Science.gov (United States)

    Singh, Arun; Mewes, Klaus; Gross, Robert E; DeLong, Mahlon R; Obeso, José A; Papa, Stella M

    2016-08-23

    Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD.

  7. Reduced striatal dopamine D2/3 receptor availability in Body Dysmorphic Disorder

    NARCIS (Netherlands)

    Vulink, Nienke C; Planting, Robin S; Figee, Martijn; Booij, Jan; Denys, D.

    Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive

  8. Reduced striatal dopamine D2/3 receptor availability in Body Dysmorphic Disorder

    NARCIS (Netherlands)

    Vulink, Nienke C.; Planting, Robin S.; Figee, Martijn; Booij, Jan; Denys, Damiaan

    2016-01-01

    Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive

  9. Ciliary neurotrophic factor protects striatal neurons against excitotoxicity by enhancing glial glutamate uptake.

    Directory of Open Access Journals (Sweden)

    Corinne Beurrier

    Full Text Available Ciliary neurotrophic factor (CNTF is a potent neuroprotective cytokine in different animal models of glutamate-induced excitotoxicity, although its action mechanisms are still poorly characterized. We tested the hypothesis that an increased function of glial glutamate transporters (GTs could underlie CNTF-mediated neuroprotection. We show that neuronal loss induced by in vivo striatal injection of the excitotoxin quinolinic acid (QA was significantly reduced (by approximately 75% in CNTF-treated animals. In striatal slices, acute QA application dramatically inhibited corticostriatal field potentials (FPs, whose recovery was significantly higher in CNTF rats compared to controls (approximately 40% vs. approximately 7%, confirming an enhanced resistance to excitotoxicity. The GT inhibitor DL-threo-beta-benzyloxyaspartate greatly reduced FP recovery in CNTF rats, supporting the role of GT in CNTF-mediated neuroprotection. Whole-cell patch-clamp recordings from striatal medium spiny neurons showed no alteration of basic properties of striatal glutamatergic transmission in CNTF animals, but the increased effect of a low-affinity competitive glutamate receptor antagonist (gamma-D-glutamylglycine also suggested an enhanced GT function. These data strongly support our hypothesis that CNTF is neuroprotective via an increased function of glial GTs, and further confirms the therapeutic potential of CNTF for the clinical treatment of progressive neurodegenerative diseases involving glutamate overflow.

  10. Aberrant local striatal functional connectivity in attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Rhein, D.T. von; Oldehinkel, M.; Beckmann, C.F.; Oosterlaan, J.; Heslenfeld, D.; Hartman, C.A.; Hoekstra, P.J.; Franke, B.; Cools, R.; Buitelaar, J.K.; Mennes, M.

    2016-01-01

    BACKGROUND: Task-based and resting-state functional Magnetic Resonance Imaging (fMRI) studies report attention-deficit/hyperactivity disorder (ADHD)-related alterations in brain regions implicated in cortico-striatal networks. We assessed whether ADHD is associated with changes in the brain's global

  11. Aberrant local striatal functional connectivity in attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    von Rhein, Daniel; Oldehinkel, Marianne; Beckmann, Christian F.; Oosterlaan, Jaap; Heslenfeld, Dirk; Hartman, Catharina A.; Hoekstra, Pieter J.; Franke, Barbara; Cools, Roshan; Buitelaar, Jan K.; Mennes, Maarten

    Background: Task-based and resting-state functional Magnetic Resonance Imaging (fMRI) studies report attention-deficit/hyperactivity disorder (ADHD)-related alterations in brain regions implicated in cortico-striatal networks. We assessed whether ADHD is associated with changes in the brain's global

  12. Fronto-striatal glutamate in autism spectrum disorder and obsessive compulsive disorder

    NARCIS (Netherlands)

    Naaijen, Jilly; Zwiers, Marcel P.; Amiri, Houshang; Williams, Steven C R; Durston, Sarah; Oranje, Bob; Brandeis, Daniel; Boecker-Schlier, Regina; Ruf, Matthias; Wolf, Isabella; Banaschewski, Tobias; Glennon, Jeffrey C.; Franke, Barbara; Buitelaar, Jan K.; Lythgoe, David J

    2017-01-01

    Autism spectrum disorders (ASDs) and obsessive compulsive disorder (OCD) are often comorbid with the overlap based on compulsive behaviors. Although previous studies suggest glutamatergic deficits in fronto-striatal brain areas in both disorders, this is the first study to directly compare the

  13. Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Naaijen, J.; Forde, N.J.; Lythgoe, D.J.; Akkermans, S.E.A.; Openneer, T.J.; Dietrich, A.; Zwiers, M.P.; Hoekstra, P.J.; Buitelaar, J.K.

    2017-01-01

    OBJECTIVE: Both Tourette's disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) have been related to abnormalities in glutamatergic neurochemistry in the fronto-striatal circuitry. TD and ADHD often co-occur and the neural underpinnings of this co-occurrence have been insufficiently

  14. Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Naaijen, Jilly; Forde, Natalie J.; Lythgoe, David J.; Akkermans, Sophie E. A.; Openneer, Thaira J. C.; Dietrich, Andrea; Zwiers, Marcel P.; Hoekstra, Pieter J.; Buitelaar, Jan K.

    2017-01-01

    Objective: Both Tourette's disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) have been related to abnormalities in glutamatergic neurochemistry in the fronto-striatal circuitry. TD and ADHD often co-occur and the neural underpinnings of this co-occurrence have been insufficiently

  15. De Novo Mutations in PDE10A Cause Childhood-Onset Chorea with Bilateral Striatal Lesions

    NARCIS (Netherlands)

    Mencacci, N.E.; Kamsteeg, E.J.; Nakashima, K.; R'Bibo, L.; Lynch, D.S.; Balint, B.; Willemsen, M.A.A.P.; Adams, M.E.; Wiethoff, S.; Suzuki, K.; Davies, C.H.; Ng, J.; Meyer, E.; Veneziano, L.; Giunti, P.; Hughes, D.; Raymond, F.L.; Carecchio, M.; Zorzi, G.; Nardocci, N.; Barzaghi, C.; Garavaglia, B.; Salpietro, V.; Hardy, J.; Pittman, A.M.; Houlden, H.; Kurian, M.A.; Kimura, H.; Vissers, L.E.L.M.; Wood, N.W.; Bhatia, K.P.

    2016-01-01

    Chorea is a hyperkinetic movement disorder resulting from dysfunction of striatal medium spiny neurons (MSNs), which form the main output projections from the basal ganglia. Here, we used whole-exome sequencing to unravel the underlying genetic cause in three unrelated individuals with a very

  16. Cannabinoid-1 receptor antagonist rimonabant (SR141716) increases striatal dopamine D2 receptor availability

    NARCIS (Netherlands)

    Crunelle, Cleo L.; van de Giessen, Elsmarieke; Schulz, Sybille; Vanderschuren, Louk J. M. J.; de Bruin, Kora; van den Brink, Wim; Booij, Jan

    2013-01-01

    The cannabinoid 1 receptor antagonist rimonabant (SR141716) alters rewarding properties and intake of food and drugs. Additionally, striatal dopamine D2 receptor (DRD2) availability has been implicated in reward function. This study shows that chronic treatment of rats with rimonabant (1.0 and

  17. Apathy and striatal dopamine defects in non-demented patients with Parkinson's disease.

    Science.gov (United States)

    Chung, Su Jin; Lee, Jae Jung; Ham, Jee Hyun; Lee, Phil Hyu; Sohn, Young H

    2016-02-01

    Apathy is a common, disabling symptom in Parkinson's disease (PD). The mechanisms underlying apathy in PD are still unclear, although they may be related to dysfunction in the meso-cortico-limbic circuit, including the ventral striatum. Thus, we performed this study to investigate whether dopamine depletion in the ventral striatum contributes to apathy in PD. We conducted a survey of the degree of apathy (using the Korean version of the Apathy Evaluation Scale, AES-S) in 108 non-demented patients with PD who underwent dopamine transporter (DAT) positron emission tomography scans as an initial diagnostic work-up. Patients with AES-S scores of 37 or higher were defined as having apathetic PD. The Beck Depression Inventory (BDI) was administered to assess the severity of depression. Patients with BDI scores of 15 or higher were regarded as having depression. Apathetic patients (n = 34) tended to exhibit higher BDI scores than non-apathetic patients (n = 74); however, other clinical variables were comparable between the two groups. DAT activity in the striatal sub-regions was also similar between the two groups. Selecting only non-depressed patients, including 20 apathetic and 47 non-apathetic patients, did not alter the results. This study demonstrated that the pattern of striatal dopamine depletion does not contribute to the degree of apathy in early PD. Apathy in PD may be associated with extra-striatal lesions that accompany PD rather than striatal dopaminergic deficits. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Apathy and striatal dopamine transporter levels in de-novo, untreated Parkinson's disease patients.

    Science.gov (United States)

    Santangelo, Gabriella; Vitale, Carmine; Picillo, Marina; Cuoco, Sofia; Moccia, Marcello; Pezzella, Domenica; Erro, Roberto; Longo, Katia; Vicidomini, Caterina; Pellecchia, Maria Teresa; Amboni, Marianna; Brunetti, Arturo; Salvatore, Marco; Barone, Paolo; Pappatà, Sabina

    2015-05-01

    Apathy is a neuropsychiatric symptom in Parkinson's Disease (PD) which has a negative impact on quality of life and might be related in part to damage of presynaptic dopaminergic system. Little is known about relationship between striatal dopamine levels and apathy in PD patients without dementia and/or depression. The aim of the present study was to investigate the relationship between "pure apathy" and striatal dopamine uptake in untreated, drug-naïve PD patients without clinically significant dementia and/or depression. Fourteen PD patients with pure apathy and 14 PD patients without apathy, matched for age, side of motor symptoms at onset, motor disability and disease duration, underwent both neuropsychological and behavioral examination including self-rated version of the Apathy Evaluation Scale (AES-S). All patients underwent 123 I-FP-CIT (DaT-SCAN) SPECT to assess dopamine transporter (DAT) striatal uptake. PD patients with apathy showed lower DAT levels in the striatum than non-apathetic patients. After Bonferroni correction the difference between groups was significant in the right caudate. Apathy is associated with reduced striatal dopamine transporter levels, independent of motor disability and depression in non-demented PD patients. These findings suggest that dysfunction of dopaminergic innervation in the striatum and particularly in the right caudate may contribute to development of apathy in early PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Frizzled3 controls axonal polarity and intermediate target entry during striatal pathway development

    NARCIS (Netherlands)

    Morello, Francesca; Prasad, Asheeta A.; Rehberg, Kati; Baptista Vieira de Sá, Renata; Antón-Bolaños, Noelia; Leyva-Diaz, Eduardo; Adolfs, Youri; Tissir, Fadel; López-Bendito, Guillermina; Pasterkamp, R. Jeroen

    2015-01-01

    The striatum is a large brain nucleus with an important role in the control of movement and emotions.Mediumspiny neurons (MSNs) are striatal output neurons forming prominent descending axon tracts that target different brain nuclei. However, how MSN axon tracts in the forebrain develop remains

  20. Different correlation patterns of cholinergic and GABAergic interneurons with striatal projection neurons

    Directory of Open Access Journals (Sweden)

    Avital eAdler

    2013-09-01

    Full Text Available The striatum is populated by a single projection neuron group, the medium spiny neurons (MSNs, and several groups of interneurons. Two of the electrophysiologically well-characterized striatal interneuron groups are the tonically active neurons (TANs, which are presumably cholinergic interneurons, and the fast spiking interneurons (FSIs, presumably parvalbumin (PV expressing GABAergic interneurons. To better understand striatal processing it is thus crucial to define the functional relationship between MSNs and these interneurons in the awake and behaving animal. We used multiple electrodes and standard physiological methods to simultaneously record MSN spiking activity and the activity of TANs or FSIs from monkeys engaged in a classical conditioning paradigm. All three cell populations were highly responsive to the behavioral task. However, they displayed different average response profiles and a different degree of response synchronization (signal correlation. TANs displayed the most transient and synchronized response, MSNs the most diverse and sustained response and FSIs were in between on both parameters. We did not find evidence for direct monosynaptic connectivity between the MSNs and either the TANs or the FSIs. However, while the cross correlation histograms of TAN to MSN pairs were flat, those of FSI to MSN displayed positive asymmetrical broad peaks. The FSI-MSN correlogram profile implies that the spikes of MSNs follow those of FSIs and both are driven by a common, most likely cortical, input. Thus, the two populations of striatal interneurons are probably driven by different afferents and play complementary functional roles in the physiology of the striatal microcircuit.

  1. Glutamine triggers long-lasting increase in striatal network activity in vitro.

    Science.gov (United States)

    Fleischer, Wiebke; Theiss, Stephan; Schnitzler, Alfons; Sergeeva, Olga

    2017-04-01

    Accumulation of ammonium and glutamine in blood and brain is a key factor in hepatic encephalopathy (HE) - a neuropsychiatric syndrome characterized by various cognitive and motor deficits. MRI imaging identified abnormalities notably in the basal ganglia of HE patients, including its major input station, the striatum. While neurotoxic effects of ammonia have been extensively studied, glutamine is primarily perceived as "detoxified" form of ammonia. We applied ammonium and glutamine to striatal and cortical cells from newborn rats cultured on microelectrode arrays. Glutamine, but not ammonium significantly increased spontaneous spike rate with a long-lasting excitation outlasting washout. This effect was more prominent in striatal than in cortical cultures. Calcium imaging revealed that glutamine application caused a rise in intracellular calcium that depended both on system A amino acid transport and activation of ionotropic glutamate receptors. This pointed to downstream glutamate release that was triggered by intracellular glutamine. Using an enzymatic assay kit we confirmed glutamine-provoked glutamate release from striatal cells. Real-time PCR and immunocytochemistry demonstrated the presence of vesicular glutamate transporters (VGLUT1 and VGLUT2) necessary for synaptic glutamate release in striatal neurons. We conclude that extracellular glutamine is taken up by neurons, triggers synaptic release of glutamate which is then taken up by astrocytes and again converted to glutamine. This feedback-loop causes a sustained long-lasting excitation of network activity. Thus, apart from ammonia also its "detoxified" form glutamine might be responsible for the neuropsychiatric symptoms in HE. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Creative cognition and dopaminergic modulation of fronto-striatal networks: Integrative review and research agenda.

    Science.gov (United States)

    Boot, Nathalie; Baas, Matthijs; van Gaal, Simon; Cools, Roshan; De Dreu, Carsten K W

    2017-07-01

    Creative cognition is key to human functioning yet the underlying neurobiological mechanisms are sparsely addressed and poorly understood. Here we address the possibility that creative cognition is a function of dopaminergic modulation in fronto-striatal brain circuitries. It is proposed that (i) creative cognition benefits from both flexible and persistent processing, (ii) striatal dopamine and the integrity of the nigrostriatal dopaminergic pathway is associated with flexible processing, while (iii) prefrontal dopamine and the integrity of the mesocortical dopaminergic pathway is associated with persistent processing. We examine this possibility in light of studies linking creative ideation, divergent thinking, and creative problem-solving to polymorphisms in dopamine receptor genes, indirect markers and manipulations of the dopaminergic system, and clinical populations with dysregulated dopaminergic activity. Combined, studies suggest a functional differentiation between striatal and prefrontal dopamine: moderate (but not low or high) levels of striatal dopamine benefit creative cognition by facilitating flexible processes, and moderate (but not low or high) levels of prefrontal dopamine enable persistence-driven creativity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Diversity in Long-Term Synaptic Plasticity at Inhibitory Synapses of Striatal Spiny Neurons

    Science.gov (United States)

    Rueda-Orozco, Pavel E.; Mendoza, Ernesto; Hernandez, Ricardo; Aceves, Jose J.; Ibanez-Sandoval, Osvaldo; Galarraga, Elvira; Bargas, Jose

    2009-01-01

    Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term…

  4. Impaired dual tasking in Parkinson's disease is associated with reduced focusing of cortico-striatal activity.

    Science.gov (United States)

    Nieuwhof, Freek; Bloem, Bastiaan R; Reelick, Miriam F; Aarts, Esther; Maidan, Inbal; Mirelman, Anat; Hausdorff, Jeffrey M; Toni, Ivan; Helmich, Rick C

    2017-05-01

    See Bell et al. (doi:10.1093/awx063) for a scientific commentary on this article. Impaired dual tasking, namely the inability to concurrently perform a cognitive and a motor task (e.g. 'stops walking while talking'), is a largely unexplained and frequent symptom of Parkinson's disease. Here we consider two circuit-level accounts of how striatal dopamine depletion might lead to impaired dual tasking in patients with Parkinson's disease. First, the loss of segregation between striatal territories induced by dopamine depletion may lead to dysfunctional overlaps between the motor and cognitive processes usually implemented in parallel cortico-striatal circuits. Second, the known dorso-posterior to ventro-anterior gradient of dopamine depletion in patients with Parkinson's disease may cause a funnelling of motor and cognitive processes into the relatively spared ventro-anterior putamen, causing a neural bottleneck. Using functional magnetic resonance imaging, we measured brain activity in 19 patients with Parkinson's disease and 26 control subjects during performance of a motor task (auditory-cued ankle movements), a cognitive task (implementing a switch-stay rule), and both tasks simultaneously (dual task). The distribution of task-related activity respected the known segregation between motor and cognitive territories of the putamen in both groups, with motor-related responses in the dorso-posterior putamen and task switch-related responses in the ventro-anterior putamen. During dual task performance, patients made more motor and cognitive errors than control subjects. They recruited a striatal territory (ventro-posterior putamen) not engaged during either the cognitive or the motor task, nor used by controls. Relatively higher ventro-posterior putamen activity in controls was associated with worse dual task performance. These observations suggest that dual task impairments in Parkinson's disease are related to reduced spatial focusing of striatal activity. This

  5. Extrastriatal binding of [¹²³I]FP-CIT in the thalamus and pons

    DEFF Research Database (Denmark)

    Koch, Walter; Unterrainer, Marcus; Xiong, Guoming

    2014-01-01

    PURPOSE: Apart from binding to the dopamine transporter (DAT), [(123)I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate...... extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. METHODS: SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes...... of interest analysis for the thalamus and the pons. Data were examined for gender and age effects as well as for potential influence of striatal DAT radiotracer binding. RESULTS: Thalamic binding was significantly higher than pons binding. Partial correlations showed an influence of putaminal DAT binding...

  6. Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.

    Directory of Open Access Journals (Sweden)

    Nicola J Platt

    Full Text Available Mutations in, or elevated dosage of, SNCA, the gene for α-synuclein (α-syn, cause familial Parkinson's disease (PD. Mouse lines overexpressing the mutant human A53Tα-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of α-syn, and deficits in dopamine-dependent corticostriatal plasticity, which, in the absence of overt nigrostriatal degeneration, suggest there are age-related deficits in striatal dopamine (DA signalling. In addition A53Tα-syn overexpression in cultured rodent neurons has been reported to inhibit transmitter release. Therefore here we have characterized for the first time DA release in the striatum of mice overexpressing human A53Tα-syn, and explored whether A53Tα-syn overexpression causes deficits in the release of DA. We used fast-scan cyclic voltammetry to detect DA release at carbon-fibre microelectrodes in acute striatal slices from two different lines of A53Tα-syn-overexpressing mice, at up to 24 months. In A53Tα-syn overexpressors, mean DA release evoked by a single stimulus pulse was not different from wild-types, in either dorsal striatum or nucleus accumbens. However the frequency responsiveness of DA release was slightly modified in A53Tα-syn overexpressors, and in particular showed slight deficiency when the confounding effects of striatal ACh acting at presynaptic nicotinic receptors (nAChRs were antagonized. The re-release of DA was unmodified after single-pulse stimuli, but after prolonged stimulation trains, A53Tα-syn overexpressors showed enhanced recovery of DA release at old age, in keeping with elevated striatal DA content. In summary, A53Tα-syn overexpression in mice causes subtle changes in the regulation of DA release in the striatum. While modest, these modifications may indicate or contribute to striatal dysfunction.

  7. Youth at risk for obesity show greater activation of striatal and somatosensory regions to food.

    Science.gov (United States)

    Stice, Eric; Yokum, Sonja; Burger, Kyle S; Epstein, Leonard H; Small, Dana M

    2011-03-23

    Obese humans, compared with normal-weight humans, have less striatal D2 receptors and striatal response to food intake; weaker striatal response to food predicts weight gain for individuals at genetic risk for reduced dopamine (DA) signaling, consistent with the reward-deficit theory of obesity. Yet these may not be initial vulnerability factors, as overeating reduces D2 receptor density, D2 sensitivity, reward sensitivity, and striatal response to food. Obese humans also show greater striatal, amygdalar, orbitofrontal cortex, and somatosensory region response to food images than normal-weight humans do, which predicts weight gain for those not at genetic risk for compromised dopamine signaling, consonant with the reward-surfeit theory of obesity. However, after pairings of palatable food intake and predictive cues, DA signaling increases in response to the cues, implying that eating palatable food contributes to increased responsivity. Using fMRI, we tested whether normal-weight adolescents at high- versus low-risk for obesity showed aberrant activation of reward circuitry in response to receipt and anticipated receipt of palatable food and monetary reward. High-risk youth showed greater activation in the caudate, parietal operculum, and frontal operculum in response to food intake and in the caudate, putamen, insula, thalamus, and orbitofrontal cortex in response to monetary reward. No differences emerged in response to anticipated food or monetary reward. Data indicate that youth at risk for obesity show elevated reward circuitry responsivity in general, coupled with elevated somatosensory region responsivity to food, which may lead to overeating that produces blunted dopamine signaling and elevated responsivity to food cues.

  8. Functional role for cortical-striatal circuitry in modulating alcohol self-administration.

    Science.gov (United States)

    Jaramillo, Anel A; Randall, Patrick A; Stewart, Spencer; Fortino, Brayden; Van Voorhies, Kalynn; Besheer, Joyce

    2018-03-01

    The cortical-striatal brain circuitry is heavily implicated in drug-use. As such, the present study investigated the functional role of cortical-striatal circuitry in modulating alcohol self-administration. Given that a functional role for the nucleus accumbens core (AcbC) in modulating alcohol-reinforced responding has been established, we sought to test the role of cortical brain regions with afferent projections to the AcbC: the medial prefrontal cortex (mPFC) and the insular cortex (IC). Long-Evans rats were trained to self-administer alcohol (15% alcohol (v/v)+2% sucrose (w/v)) during 30 min sessions. To test the functional role of the mPFC or IC, we utilized a chemogenetic technique (hM4D i -Designer Receptors Activation by Designer Drugs) to silence neuronal activity prior to an alcohol self-administration session. Additionally, we chemogenetically silenced mPFC→AcbC or IC→AcbC projections, to investigate the role of cortical-striatal circuitry in modulating alcohol self-administration. Chemogenetically silencing the mPFC decreased alcohol self-administration, while silencing the IC increased alcohol self-administration, an effect absent in mCherry-Controls. Interestingly, silencing mPFC→AcbC projections had no effect on alcohol self-administration. In contrast, silencing IC→AcbC projections decreased alcohol self-administration, in a reinforcer-specific manner as there was no effect in rats trained to self-administer sucrose (0.8%, w/v). Additionally, no change in self-administration was observed in the mCherry-Controls. Together these data demonstrate the complex role of the cortical-striatal circuitry while implicating a role for the insula-striatal circuit in modulating ongoing alcohol self-administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Survey of electrochemical metal winning processes. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Vaaler, L.E.

    1979-03-01

    The subject program was undertaken to find electrometallurgical technology that could be developed into energy saving commercial metal winning processes. Metals whose current production processes consume significant energy (excepting copper and aluminum) are magnesium, zinc, lead, chromium, manganese, sodium, and titanium. The technology of these metals, with the exception of titanium, was reviewed. Growth of titanium demand has been too small to justify the installation of an electrolyte process that has been developed. This fact and the uncertainty of estimates of future demand dissuaded us from reviewing titanium technology. Opportunities for developing energy saving processes were found for magnesium, zinc, lead, and sodium. Costs for R and D and demonstration plants have been estimated. It appeared that electrolytic methods for chromium and manganese cannot compete energywise or economically with the pyrometallurgical methods of producing the ferroalloys, which are satisfactory for most uses of chromium and manganese.

  10. Proceedings of the WIN-Global 2008 conference

    International Nuclear Information System (INIS)

    2008-01-01

    WiN-France hosted the 16. WIN-Global conference May 26-30, 2008, in Marseille, France. The conference was attended by over 150 delegates, representing 30 countries. Canadian participants, from many diverse backgrounds, attended the annual conference from AECL, Bruce Power, CNSC, NB Power and OPG. The theme: Maintaining Key Competencies, Arising Key Competencies for Nuclear Energy: A Challenge and Opportunity for Diversity Development, emphasized the challenges ahead in providing a skilled workforce for the nuclear renaissance, as new build projects and a vast number of retirements are expected around the world within the next 5 years. The conference addressed such questions as 'How will nuclear, attract, develop and retain staff?' A technical tour of Marcoule invited conference attendees to visit one of: Atalante, a high level nuclear chemistry laboratory; Phenix, a fast breeding research reactor; or AVM, a vitrification plant. A subsequent technical tour visited Cadarache providing the opportunity to view ITER, the international fusion research project

  11. Process for winning uranium from wet process phosphoric acid

    International Nuclear Information System (INIS)

    1980-01-01

    A process is described for winning uranium from wet process phosphoric acid by means of liquid-liquid extraction with organic phosphoric acid esters. The process is optimised by keeping the sulphate percentage in the phosphoric acid below 2% by weight, and preferably below 0.6% by weight, as compared to P 2 O 5 in the phosphoric acid. This is achieved by adding an excess of Ba and/or Ca carbonate or sulfide solution and filtering off the formed calcium and/or barium sulphate precipitates. Solid KClO 3 is then added to the filtrate to oxidise U 4+ to U 6+ . The normal extraction procedure using organic phosphoric esters as extraction liquid, can then be applied. (Th.P.)

  12. Survival in Academy Award-winning actors and actresses.

    Science.gov (United States)

    Redelmeier, D A; Singh, S M

    2001-05-15

    Social status is an important predictor of poor health. Most studies of this issue have focused on the lower echelons of society. To determine whether the increase in status from winning an academy award is associated with long-term mortality among actors and actresses. Retrospective cohort analysis. Academy of Motion Picture Arts and Sciences. All actors and actresses ever nominated for an academy award in a leading or a supporting role were identified (n = 762). For each, another cast member of the same sex who was in the same film and was born in the same era was identified (n = 887). Life expectancy and all-cause mortality rates. All 1649 performers were analyzed; the median duration of follow-up time from birth was 66 years, and 772 deaths occurred (primarily from ischemic heart disease and malignant disease). Life expectancy was 3.9 years longer for Academy Award winners than for other, less recognized performers (79.7 vs. 75.8 years; P = 0.003). This difference was equal to a 28% relative reduction in death rates (95% CI, 10% to 42%). Adjustment for birth year, sex, and ethnicity yielded similar results, as did adjustments for birth country, possible name change, age at release of first film, and total films in career. Additional wins were associated with a 22% relative reduction in death rates (CI, 5% to 35%), whereas additional films and additional nominations were not associated with a significant reduction in death rates. The association of high status with increased longevity that prevails in the public also extends to celebrities, contributes to a large survival advantage, and is partially explained by factors related to success.

  13. Gain in Body Fat Is Associated with Increased Striatal Response to Palatable Food Cues, whereas Body Fat Stability Is Associated with Decreased Striatal Response

    Science.gov (United States)

    Yokum, Sonja

    2016-01-01

    Cross-sectional brain-imaging studies reveal that obese versus lean humans show greater responsivity of reward and attention regions to palatable food cues, but lower responsivity of reward regions to palatable food receipt. However, these individual differences in responsivity may result from a period of overeating. We conducted a repeated-measures fMRI study to test whether healthy weight adolescent humans who gained body fat over a 2 or 3 year follow-up period show an increase in responsivity of reward and attention regions to a cue signaling impending milkshake receipt and a simultaneous decrease in responsivity of reward regions to milkshake receipt versus adolescents who showed stability of or loss of body fat. Adolescents who gained body fat, who largely remained in a healthy weight range, showed increases in activation in the putamen, mid-insula, Rolandic operculum, and precuneus to a cue signaling impending milkshake receipt versus those who showed stability of or loss of body fat, though these effects were partially driven by reductions in responsivity among the latter groups. Adolescents who gained body fat reported significantly greater milkshake wanting and milkshake pleasantness ratings at follow-up compared to those who lost body fat. Adolescents who gained body fat did not show a reduction in responsivity of reward regions to milkshake receipt or changes in responsivity to receipt and anticipated receipt of monetary reward. Data suggest that initiating a prolonged period of overeating may increase striatal responsivity to food cues, and that maintaining a balance between caloric intake and expenditure may reduce striatal, insular, and Rolandic operculum responsivity. SIGNIFICANCE STATEMENT This novel, repeated-measures brain-imaging study suggests that adolescents who gained body fat over our follow-up period experienced an increase in striatal responsivity to cues for palatable foods compared to those who showed stability of or loss of body fat

  14. Windows Calorimeter Control (WinCal) system configuration control board (SCCB) operating procedure

    International Nuclear Information System (INIS)

    Westsik, G.A.

    1997-01-01

    This document describes the operating procedure for the System Configuration Control Board (SCCB) performed in support of the Windows Calorimeter Control (WinCal) system. This board will consist of representatives from Babcock and Wilcox Hanford Company Babcock and Wilcox Protec, Inc.; and Lockheed Martin Services, Inc. In accordance with agreements for the joint use of the Babcock and Wilcox Hanford Company calorimeters located in the Hanford Site Plutonium Finishing Plant (PFP) Nondestructive Assay Laboratory, concurrence regarding changes to the WinCal system will be obtained from the International Atomic Energy Agency (IAEA). Further, changes to the WinCal software will be communicated to Los Alamos National Laboratory

  15. Military Engagement and Forward Presence: Down But Not Out as Tools to Shape and Win

    Science.gov (United States)

    2016-01-01

    Summer 2000, p. 36; Robert J. Art, “Geopolitics Updated: The Strategy of Selective Engagement,” International Security, Vol. 23, No. 3, Win - ter 1998-99...MILITARY ENGAGEMENT AND FORWARD PRESENCE: DOWN BUT NOT OUT AS TOOLS TO SHAPE AND WIN John R. Deni USAWC WebsiteSSI WebsiteThis Publication U.S...OUT AS TOOLS TO SHAPE AND WIN John R. Deni January 2016 The views expressed in this report are those of the author and do not necessarily reflect

  16. Populations of striatal medium spiny neurons encode vibrotactile frequency in rats: modulation by slow wave oscillations.

    Science.gov (United States)

    Hawking, Thomas G; Gerdjikov, Todor V

    2013-01-01

    Dorsolateral striatum (DLS) is implicated in tactile perception and receives strong projections from somatosensory cortex. However, the sensory representations encoded by striatal projection neurons are not well understood. Here we characterized the contribution of DLS to the encoding of vibrotactile information in rats by assessing striatal responses to precise frequency stimuli delivered to a single vibrissa. We applied stimuli in a frequency range (45-90 Hz) that evokes discriminable percepts and carries most of the power of vibrissa vibration elicited by a range of complex fine textures. Both medium spiny neurons and evoked potentials showed tactile responses that were modulated by slow wave oscillations. Furthermore, medium spiny neuron population responses represented stimulus frequency on par with previously reported behavioral benchmarks. Our results suggest that striatum encodes frequency information of vibrotactile stimuli which is dynamically modulated by ongoing brain state.

  17. Overeating Behavior and Striatal Dopamine with 6-[18F]-Fluoro-L--Tyrosine PET

    Directory of Open Access Journals (Sweden)

    Claire E. Wilcox

    2010-01-01

    Full Text Available Eating behavior may be affected by dopamine synthesis capacity. In this study, 6-[18F]-fluoro-L--tyrosine (FMT positron emission tomography (PET uptake in striatal subregions was correlated with BMI (kg/m2 and an estimate of the frequency of prior weight loss attempts in 15 healthy subjects. BMI was negatively correlated with FMT uptake in the dorsal caudate. Although the association between BMI and FMT uptake in the dorsal caudate was not significant upon correction for age and sex, the association fell within the range of a statistical trend. Weight loss attempts divided by years trying was also negatively correlated with FMT uptake in the dorsal putamen (=.05. These results suggest an association between low dorsal striatal presynaptic dopamine synthesis capacity and overeating behavior.

  18. Effects of the modern food environment on striatal function, cognition and regulation of ingestive behavior.

    Science.gov (United States)

    Burke, Mary V; Small, Dana M

    2016-06-01

    Emerging evidence from human and animal studies suggest that consumption of palatable foods rich in fat and/or carbohydrates may produce deleterious influences on brain function independently of body weight or metabolic disease. Here we consider two mechanisms by which diet can impact striatal circuits to amplify food cue reactivity and impair inhibitory control. First, we review findings demonstrating that the energetic properties of foods regulate nucleus accumbens food cue reactivity, a demonstrated predictor of weight gain susceptibility, which is then sensitized by chronic consumption of an energy dense diet. Second, we consider evidence for diet-induced adaptations in dorsal striatal dopamine signaling that is associated with impaired inhibitory control and negative outcome learning.

  19. The need of a win-win regulation regarding the harmonization of advantages for the renewable energy sector and the concerns about the environment

    Directory of Open Access Journals (Sweden)

    Moraru Dan

    2015-06-01

    Full Text Available The main theme of this paper is the evolution of theories and suppositions regarding environment and growth. The sustainable green growth and the sustainable green capitalism concepts have attracted the interest and imagination of policy makers and industry, and also stimulated many exciting new ideas and practical actions such as the “triple bottom line” which refers to harmonizing and balancing out the three interests that are linked with sustainable business: economic, environmental and social ones. The policy has to create a workable association between what the government can ensure and not tax and what it cannot ensure and must tax. In this manner we get a win-win regulation meaning that both sides win. National and supranational policies are part of the macro-level governance and very relevant for the sustainable development of the EU Member States and for the stability of the EU itself.

  20. Prolonged striatal disinhibition as a chronic animal model of tic disorders.

    Science.gov (United States)

    Vinner, Esther; Israelashvili, Michal; Bar-Gad, Izhar

    2017-12-01

    Experimental findings and theoretical models have associated Tourette syndrome with abnormal striatal inhibition. The expression of tics, the hallmark symptom of this disorder, has been transiently induced in non-human primates and rodents by the injection of GABA A antagonists into the striatum, leading to temporary disinhibition. The novel chronic model of tic expression utilizes mini-osmotic pumps implanted subcutaneously in the rat's back for prolonged infusion of bicuculline into the dorsolateral striatum. Tics were expressed on the contralateral side to the infusion over a period of multiple days. Tic expression was stable, and maintained similar properties throughout the infusion period. Electrophysiological recordings revealed the existence of tic-related local field potential spikes and individual neuron activity changes that remained stable throughout the infusion period. The striatal disinhibition model provides a unique combination of face validity (tic expression) and construct validity (abnormal striatal inhibition) but is limited to sub-hour periods. The new chronic model extends the period of tic expression to multiple days and thus enables the study of tic dynamics and the effects of behavior and pharmacological agents on tic expression. The chronic model provides similar behavioral and neuronal correlates of tics as the acute striatal disinhibition model but over prolonged periods of time, thus providing a unique, basal ganglia initiated model of tic expression. Chronic expression of symptoms is the key to studying the time varying properties of Tourette syndrome and the effects of multiple internal and external factors on this disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Basal ganglia disorders associated with imbalances in the striatal striosome and matrix compartments

    Directory of Open Access Journals (Sweden)

    Jill R. Crittenden

    2011-09-01

    Full Text Available The striatum is composed principally of GABAergic, medium spiny projection neurons (MSNs that can be categorized based on their gene expression, electrophysiological profiles and input-output circuits. Major subdivisions of MSN populations include 1 those in ventromedial and dorsolateral striatal regions, 2 those giving rise to the direct and indirect pathways, and 3 those that lie in the striosome and matrix compartments. The first two classificatory schemes have enabled advances in understanding of how basal ganglia circuits contribute to disease. However, despite the large number of molecules that are differentially expressed in the striosomes or the extra-striosomal matrix, and the evidence that these compartments have different input-output connections, our understanding of how this compartmentalization contributes to striatal function is still not clear. A broad view is that the matrix contains the direct and indirect pathway MSNs that form parts of sensorimotor and associative circuits, whereas striosomes contain MSNs that receive input from parts of limbic cortex and project directly or indirectly to the dopamine-containing neurons of the substantia nigra, pars compacta. Striosomes are widely distributed within the striatum and are thought to exert global, as well as local, influences on striatal processing by exchanging information with the surrounding matrix, including through interneurons that send processes into both compartments. It has been suggested that striosomes exert and maintain limbic control over behaviors driven by surrounding sensorimotor and associative parts of the striatal matrix. Consistent with this possibility, imbalances between striosome and matrix functions have been reported in relation to neurological disorders, including Huntington’s disease, L-DOPA-induced dyskinesias, dystonia and drug addiction. Here, we consider how signaling imbalances between the striosomes and matrix might relate to symptomatology in

  2. Distinct roles for direct and indirect pathway striatal neurons in reinforcement.

    Science.gov (United States)

    Kravitz, Alexxai V; Tye, Lynne D; Kreitzer, Anatol C

    2012-06-01

    Dopamine signaling is implicated in reinforcement learning, but the neural substrates targeted by dopamine are poorly understood. We bypassed dopamine signaling itself and tested how optogenetic activation of dopamine D1 or D2 receptor–expressing striatal projection neurons influenced reinforcement learning in mice. Stimulating D1 receptor–expressing neurons induced persistent reinforcement, whereas stimulating D2 receptor–expressing neurons induced transient punishment, indicating that activation of these circuits is sufficient to modify the probability of performing future actions.

  3. Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.

    Science.gov (United States)

    Pierozan, Paula; Ferreira, Fernanda; de Lima, Bárbara Ortiz; Pessoa-Pureur, Regina

    2015-02-01

    Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 μM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N-methyl-D-aspartate (50 µM DL-AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra- and extracellular Ca(2+) chelators (10 µM BAPTA-AM and 1 mM EGTA, respectively) and Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (10 µM verapamil) are implicated in QUIN-mediated effects. Cells immunostained for the neuronal markers βIII-tubulin and microtubule-associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN-treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron-astrocyte interaction playing a role in neuroprotection. © 2014 Wiley Periodicals, Inc.

  4. The hippocampal-striatal circuit for goal-directed and habitual choice

    OpenAIRE

    Chersi, Fabian

    2014-01-01

    It is now widely accepted that one of the roles of the hippocampus is to maintain episodic spatial representations, while parallel striatal pathways contribute to both declarative and procedural value computations by encoding different input-specific outcome predictions. In this paper we investigate the use of these brain mechanisms for action selection, linking them to model-based and model-free controllers for decision making. To this aim we propose a biologically inspired computational mod...

  5. Ventral striatal dopamine synthesis capacity predicts financial extravagance in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Andrew David Lawrence

    2013-02-01

    Full Text Available Impulse control disorders (ICDs, including disordered gambling, can occur in a significant number of patients with Parkinson’s disease (PD receiving dopaminergic therapy. The neurobiology underlying susceptibility to such problems is unclear, but risk likely results from an interaction between dopaminergic medication and a pre-existing trait vulnerability. Impulse control and addictive disorders form part of a broader psychopathological spectrum of disorders, which share a common underlying genetic vulnerability, referred to as externalizing. The broad externalizing risk factor is a continuously varying trait reflecting vulnerability to various impulse control problems, manifested at the overt level by disinhibitory symptoms and at the personality level by antecedent traits such as impulsivity and novelty/sensation seeking. Trait ‘disinhibition’ is thus a core endophenotype of ICDs, and a key target for neurobiological investigation. The ventral striatal dopamine system has been hypothesized to underlie individual variation in behavioural disinhibition. Here, we examined whether individual differences in ventral striatal dopamine synthesis capacity predicted individual variation in disinhibitory temperament traits in individuals with PD. Eighteen early-stage male PD patients underwent 6-[18F]Fluoro-L-DOPA (FDOPA positron emission tomography (PET scanning to measure striatal dopamine synthesis capacity, and completed a measure of disinhibited personality. Consistent with our predictions, we found that levels of ventral, but not dorsal, striatal dopamine synthesis capacity predicted disinhibited personality, particularly a propensity for financial extravagance. Our results are consistent with recent preclinical models of vulnerability to behavioural disinhibition and addiction proneness, and provide novel insights into the neurobiology of potential vulnerability to impulse control problems in PD and other disorders.

  6. Liquid computing on and off the edge of chaos with a striatal microcircuit

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    Carlos eToledo-Suárez

    2014-11-01

    Full Text Available In reinforcement learning theories of the basal ganglia, there is a need for the expected rewards corresponding to relevant environmental states to be maintained and modified during the learning process. However, the representation of these states that allows them to be associated with reward expectations remains unclear. Previous studies have tended to rely on pre-defined partitioning of states encoded by disjunct neuronal groups or sparse topological drives. A more likely scenario is that striatal neurons are involved in the encoding of multiple different states through their spike patterns, and that an appropriate partitioning of an environment is learned on the basis of task constraints, thus minimizing the number of states involved in solving a particular task. Here we show that striatal activity is sufficient to implement a liquid state, an important prerequisite for such a computation, whereby transient patterns of striatal activity are mapped onto the relevant states. We develop a simple small scale model of the striatum which can reproduce key features of the experimentally observed activity of the major cell types of the striatum. We then use the activity of this network as input for the supervised training of four simple linear readouts to learn three different functions on a plane, where the network is stimulated with the spike coded position of the agent. We discover that the network configuration that best reproduces striatal activity statistics lies on the edge of chaos and has good performance on all three tasks, but that in general, the edge of chaosis a poor predictor of network performance.

  7. The Fast Spiking Subpopulation of Striatal Neurons Coding for Temporal Cognition of Movements

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    Bo Shen

    2017-12-01

    Full Text Available Background: Timing dysfunctions occur in a number of neurological and psychiatric disorders such as Parkinson’s disease, obsessive-compulsive disorder, autism and attention-deficit-hyperactivity disorder. Several lines of evidence show that disrupted timing processing is involved in specific fronto-striatal abnormalities. The striatum encodes reinforcement learning and procedural motion, and consequently is required to represent temporal information precisely, which then guides actions in proper sequence. Previous studies highlighted the temporal scaling property of timing-relevant striatal neurons; however, it is still unknown how this is accomplished over short temporal latencies, such as the sub-seconds to seconds range.Methods: We designed a task with a series of timing behaviors that required rats to reproduce a fixed duration with robust action. Using chronic multichannel electrode arrays, we recorded neural activity from dorso-medial striatum in 4 rats performing the task and identified modulation response of each neuron to different events. Cell type classification was performed according to a multi-criteria clustering analysis.Results: Dorso-medial striatal neurons (n = 557 were recorded, of which 113 single units were considered as timing-relevant neurons, especially the fast-spiking subpopulation that had trial–to–trial ramping up or ramping down firing modulation during the time estimation period. Furthermore, these timing-relevant striatal neurons had to calibrate the spread of their firing pattern by rewarded experience to express the timing behavior accurately.Conclusion: Our data suggests that the dynamic activities of timing-relevant units encode information about the current duration and recent outcomes, which is needed to predict and drive the following action. These results reveal the potential mechanism of time calibration in a short temporal resolution, which may help to explain the neural basis of motor coordination

  8. DISC1 and striatal volume: a potential risk phenotype for mental illness

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    M. Mallar eChakravarty

    2012-06-01

    Full Text Available Disrupted-in-schizophrenia 1 was originally discovered in a large Scottish family with abnormally high rates of severe mental illness, including schizophrenia, bipolar disorder, and depression. An accumulating body of evidence from genetic, postmortem, and animal data supports a role for DISC1 in different forms of mental illness. DISC1 may play an important role in determining structure and function of several brain regions. One brain region of particular importance for several mental disorders is the striatum, and DISC1 mutant mice have demonstrated an increase in dopamine (D2 receptors in this structure. However, association between DISC1 functional polymorphisms and striatal structure have not been examined in humans to our knowledge. We, therefore hypothesized that there would be a relationship between human striatal volume and DISC1 genotype, specifically in the Leu607Phe (rs6675281 and Ser704Cys (rs821618 single nucleotide polymorphisms. We tested our hypothesis by automatically identifying the striatum in fifty-four healthy volunteers recruited for this study. We also performed an exploratory analysis of cortical thickness, cortical surface area, and structure volume. Our results demonstrate that Phe allele carriers have larger striatal volume bilaterally (left striatum: p=0.017; right striatum: p=0.016. From the exploratory analyses we found that Phe carriers also had larger right hemisphere volumes and right occipital lobe surface area (p=0.014 compared to LeuLeu homozygotes (p=0.0074. However, these exploratory findings do not survive a conservative correction for multiple comparisons. Our findings demonstrate that a functional DISC1 variant influences striatal volumes. Taken together with animal data that this gene influences D2 receptor levels in striatum, a key risk pathway for mental illnesses such as schizophrenia and bipolar disorder may be conferred via DISC1’s effects on the striatum .

  9. Cortico-striatal spike-timing dependent plasticity after activation of subcortical pathways

    Directory of Open Access Journals (Sweden)

    Jan M Schulz

    2010-07-01

    Full Text Available Cortico-striatal spike-timing dependent plasticity (STDP is modulated by dopamine in vitro. The present study investigated STDP in vivo using alternative procedures for modulating dopaminergic inputs. Postsynaptic potentials (PSP were evoked in intracellularly recorded spiny neurons by electrical stimulation of the contralateral motor cortex. PSPs often consisted of up to three distinct components, likely representing distinct cortico-striatal pathways. After baseline recording, bicuculline (BIC was ejected into the superior colliculus (SC to disinhibit visual pathways to the dopamine cells and striatum. Repetitive cortical stimulation (~60; 0.2 Hz was then paired with postsynaptic spike discharge induced by an intracellular current pulse, with each pairing followed 250 ms later by a light flash to the contralateral eye (n=13. Changes in PSPs, measured as the maximal slope normalised to 5 min pre, ranged from potentiation (~120% to depression (~80%. The determining factor was the relative timing between PSP components and spike: PSP components coinciding or closely following the spike tended towards potentiation, whereas PSP components preceding the spike were depressed. Importantly, STDP was only seen in experiments with successful BIC-mediated disinhibition (n=10. Cortico-striatal high-frequency stimulation (50 pulses at 100 Hz followed 100 ms later by a light flash did not induce more robust synaptic plasticity (n=9. However, an elevated post-light spike rate correlated with depression across plasticity protocols (R2=0.55, p=0.009, n=11 active neurons. These results confirm that the direction of cortico-striatal plasticity is determined by the timing of pre- and postsynaptic activity and that synaptic modification is dependent on the activation of additional subcortical inputs.

  10. Striatal activation by optogenetics induces dyskinesias in the 6-hydroxydopamine rat model of Parkinson disease.

    Science.gov (United States)

    F Hernández, Ledia; Castela, Ivan; Ruiz-DeDiego, Irene; Obeso, Jose A; Moratalla, Rosario

    2017-04-01

    Long-term levodopa (l-dopa) treatment is associated with the development of l-dopa-induced dyskinesias in the majority of patients with Parkinson disease (PD). The etiopathogonesis and mechanisms underlying l-dopa-induced dyskinesias are not well understood. We used striatal optogenetic stimulation to induce dyskinesias in a hemiparkinsonian model of PD in rats. Striatal dopamine depletion was induced unilaterally by 6-hydroxydopamine injection into the medial forebrain bundle. For the optogenetic manipulation, we injected adeno-associated virus particles expressing channelrhodopsin to stimulate striatal medium spiny neurons with a laser source. Simultaneous optical activation of medium spiny neurons of the direct and indirect striatal pathways in the 6-hydroxydopamine lesion but l-dopa naïve rats induced involuntary movements similar to l-dopa-induced dyskinesias, labeled here as optodyskinesias. Noticeably, optodyskinesias were facilitated by l-dopa in animals that did not respond initially to the laser stimulation. In general, optodyskinesias lasted while the laser stimulus was applied, but in some instances remained ongoing for a few seconds after the laser was off. Postmortem tissue analysis revealed increased FosB expression, a molecular marker of l-dopa-induced dyskinesias, primarily in medium spiny neurons of the direct pathway in the dopamine-depleted hemisphere. Selective optogenetic activation of the dorsolateral striatum elicits dyskinesias in the 6-hydroxydopamine rat model of PD. This effect was associated with a preferential activation of the direct striato-nigral pathway. These results potentially open new avenues in the understanding of mechanisms involved in l-dopa-induced dyskinesias. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  11. Increased TRPC5 glutathionylation contributes to striatal neuron loss in Huntington's disease.

    Science.gov (United States)

    Hong, Chansik; Seo, Hyemyung; Kwak, Misun; Jeon, Jeha; Jang, Jihoon; Jeong, Eui Man; Myeong, Jongyun; Hwang, Yu Jin; Ha, Kotdaji; Kang, Min Jueng; Lee, Kyu Pil; Yi, Eugene C; Kim, In-Gyu; Jeon, Ju-Hong; Ryu, Hoon; So, Insuk

    2015-10-01

    Aberrant glutathione or Ca(2+) homeostasis due to oxidative stress is associated with the pathogenesis of neurodegenerative disorders. The Ca(2+)-permeable transient receptor potential cation (TRPC) channel is predominantly expressed in the brain, which is sensitive to oxidative stress. However, the role of the TRPC channel in neurodegeneration is not known. Here, we report a mechanism of TRPC5 activation by oxidants and the effect of glutathionylated TRPC5 on striatal neurons in Huntington's disease. Intracellular oxidized glutathione leads to TRPC5 activation via TRPC5 S-glutathionylation at Cys176/Cys178 residues. The oxidized glutathione-activated TRPC5-like current results in a sustained increase in cytosolic Ca(2+), activated calmodulin-dependent protein kinase and the calpain-caspase pathway, ultimately inducing striatal neuronal cell death. We observed an abnormal glutathione pool indicative of an oxidized state in the striatum of Huntington's disease transgenic (YAC128) mice. Increased levels of endogenous TRPC5 S-glutathionylation were observed in the striatum in both transgenic mice and patients with Huntington's disease. Both knockdown and inhibition of TRPC5 significantly attenuated oxidation-induced striatal neuronal cell death. Moreover, a TRPC5 blocker improved rearing behaviour in Huntington's disease transgenic mice and motor behavioural symptoms in littermate control mice by increasing striatal neuron survival. Notably, low levels of TRPC1 increased the formation of TRPC5 homotetramer, a highly Ca(2+)-permeable channel, and stimulated Ca(2+)-dependent apoptosis in Huntington's disease cells (STHdh(Q111/111)). Taken together, these novel findings indicate that increased TRPC5 S-glutathionylation by oxidative stress and decreased TRPC1 expression contribute to neuronal damage in the striatum and may underlie neurodegeneration in Huntington's disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain

  12. Increased TRPC5 glutathionylation contributes to striatal neuron loss in Huntington’s disease

    Science.gov (United States)

    Hong, Chansik; Seo, Hyemyung; Kwak, Misun; Jeon, Jeha; Jang, Jihoon; Jeong, Eui Man; Myeong, Jongyun; Hwang, Yu Jin; Ha, Kotdaji; Kang, Min Jueng; Lee, Kyu Pil; Yi, Eugene C.; Kim, In-Gyu; Jeon, Ju-Hong

    2015-01-01

    Aberrant glutathione or Ca2+ homeostasis due to oxidative stress is associated with the pathogenesis of neurodegenerative disorders. The Ca2+-permeable transient receptor potential cation (TRPC) channel is predominantly expressed in the brain, which is sensitive to oxidative stress. However, the role of the TRPC channel in neurodegeneration is not known. Here, we report a mechanism of TRPC5 activation by oxidants and the effect of glutathionylated TRPC5 on striatal neurons in Huntington’s disease. Intracellular oxidized glutathione leads to TRPC5 activation via TRPC5 S-glutathionylation at Cys176/Cys178 residues. The oxidized glutathione-activated TRPC5-like current results in a sustained increase in cytosolic Ca2+, activated calmodulin-dependent protein kinase and the calpain-caspase pathway, ultimately inducing striatal neuronal cell death. We observed an abnormal glutathione pool indicative of an oxidized state in the striatum of Huntington’s disease transgenic (YAC128) mice. Increased levels of endogenous TRPC5 S-glutathionylation were observed in the striatum in both transgenic mice and patients with Huntington’s disease. Both knockdown and inhibition of TRPC5 significantly attenuated oxidation-induced striatal neuronal cell death. Moreover, a TRPC5 blocker improved rearing behaviour in Huntington’s disease transgenic mice and motor behavioural symptoms in littermate control mice by increasing striatal neuron survival. Notably, low levels of TRPC1 increased the formation of TRPC5 homotetramer, a highly Ca2+-permeable channel, and stimulated Ca2+-dependent apoptosis in Huntington’s disease cells (STHdhQ111/111). Taken together, these novel findings indicate that increased TRPC5 S-glutathionylation by oxidative stress and decreased TRPC1 expression contribute to neuronal damage in the striatum and may underlie neurodegeneration in Huntington’s disease. PMID:26133660

  13. Alterations in Striatal Synaptic Transmission are Consistent across Genetic Mouse Models of Huntington's Disease

    Directory of Open Access Journals (Sweden)

    Damian M Cummings

    2010-05-01

    Full Text Available Since the identification of the gene responsible for HD (Huntington's disease, many genetic mouse models have been generated. Each employs a unique approach for delivery of the mutated gene and has a different CAG repeat length and background strain. The resultant diversity in the genetic context and phenotypes of these models has led to extensive debate regarding the relevance of each model to the human disorder. Here, we compare and contrast the striatal synaptic phenotypes of two models of HD, namely the YAC128 mouse, which carries the full-length huntingtin gene on a yeast artificial chromosome, and the CAG140 KI*** (knock-in mouse, which carries a human/mouse chimaeric gene that is expressed in the context of the mouse genome, with our previously published data obtained from the R6/2 mouse, which is transgenic for exon 1 mutant huntingtin. We show that striatal MSNs (medium-sized spiny neurons in YAC128 and CAG140 KI mice have similar electrophysiological phenotypes to that of the R6/2 mouse. These include a progressive increase in membrane input resistance, a reduction in membrane capacitance, a lower frequency of spontaneous excitatory postsynaptic currents and a greater frequency of spontaneous inhibitory postsynaptic currents in a subpopulation of striatal neurons. Thus, despite differences in the context of the inserted gene between these three models of HD, the primary electrophysiological changes observed in striatal MSNs are consistent. The outcomes suggest that the changes are due to the expression of mutant huntingtin and such alterations can be extended to the human condition.

  14. Concomitant Appearance of Pisa Syndrome and Striatal Hand in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2011-10-01

    Full Text Available Pisa syndrome is (PS usually seen in patients receiving antipsychotic drugs and characterised by lateral flexion of trunk and axial dystonia. It is believed that antipsychotic drugs lead to dopamine blockage causing PS. We describe a Parkinson’s disease patient who was doing well with levodopa/carbidopa for 3 years and developed lateral flexion of trunk. His abnormal posture used to completely improve upon lying down position. He also had striatal hand deformity suggestive of focal dystonia.

  15. Dopamine D1-like receptors depress excitatory synaptic transmissions in striatal neurons after transient forebrain ischemia.

    Science.gov (United States)

    Zhang, Yuchun; Deng, Ping; Ruan, Yiwen; Xu, Zao C

    2008-08-01

    Spiny neurons in the neostriatum are highly vulnerable to ischemia. Despite an enormous body of research suggesting that dopamine is involved in ischemia-induced neuronal loss in the striatum, it remains unclear how dopamine interacts with the glutamatergic excitotoxicity that is widely accepted as a major cause of ischemic cell death. Our study was designed to investigate the effects of dopamine D1 receptor (D1R) activation on excitatory neurotransmission in postischemic striatal neurons. We used the 4-vessel occlusion ischemia model and brain slice preparations. Whole-cell voltage-clamp recording was performed on striatal neurons to measure excitatory postsynaptic currents (EPSCs). Systemic administration of a D1R agonist after ischemia and hematoxylin/eosin staining were performed to evaluate the effects of D1R activation on ischemia-induced neuronal degeneration in the striatum. D1R activation depressed EPSCs in postischemic striatal neurons. The depression was attributable to inhibition of presynaptic release. An activator of cAMP-dependent protein kinase A (PKA) mimicked the depressive effects of D1R activation. Bath application of a PKA inhibitor blocked the depression of EPSCs, whereas intracellular postsynaptic application of the PKA inhibitor had no effect. The D1R agonist failed to reduce EPSC amplitude in the presence of an adenosine A1 receptor antagonist. Systemic administration of a D1R agonist after ischemia significantly attenuated ischemia-induced cell death in the striatum. These results indicate that D1R activation presynaptically depresses excitatory synaptic transmission in striatal neurons after ischemia through activation of PKA and adenosine A1 receptors and thus demonstrate a novel mechanism of D1R-mediated protection against ischemia.

  16. Motor Skill Learning Is Associated with Phase-Dependent Modifications in the Striatal cAMP/PKA/DARPP-32 Signaling Pathway in Rodents.

    Directory of Open Access Journals (Sweden)

    Yu Qian

    Full Text Available Abundant evidence points to a key role of dopamine in motor skill learning, although the underlying cellular and molecular mechanisms are still poorly understood. Here, we used a skilled-reaching paradigm to first examine changes in the expression of the plasticity-related gene Arc to map activity in cortico-striatal circuitry during different phases of motor skill learning in young animals. In the early phase, Arc mRNA was significantly induced in the medial prefrontal cortex (mPFC, cingulate cortex, primary motor cortex, and striatum. In the late phase, expression of Arc did not change in most regions, except in the mPFC and dorsal striatum. In the second series of experiments, we studied the learning-induced changes in the phosphorylation state of dopamine and cAMP-regulated phosphoprotein, 32k Da (DARPP-32. Western blot analysis of the phosphorylation state of DARPP-32 and its downstream target cAMP response element-binding protein (CREB in the striatum revealed that the early, but not late, phase of motor skill learning was associated with increased levels of phospho-Thr34-DARPP-32 and phospho-Ser133-CREB. Finally, we used the DARPP-32 knock-in mice with a point mutation in the Thr34 regulatory site (i.e., protein kinase A site to test the significance of this pathway in motor skill learning. In accordance with our hypothesis, inhibition of DARPP-32 activity at the Thr34 regulatory site strongly attenuated the motor learning rate and skilled reaching performance of mice. These findings suggest that the cAMP/PKA/DARPP-32 signaling pathway is critically involved in the acquisition of novel motor skills, and also demonstrate a dynamic shift in the contribution of cortico-striatal circuitry during different phases of motor skill learning.

  17. Does a Least-Preferred Candidate Win a Seat? A Comparison of Three Electoral Systems

    Directory of Open Access Journals (Sweden)

    Yoichi Hizen

    2015-01-01

    Full Text Available In this paper, the differences between two variations of proportional representation (PR, open-list PR and closed-list PR, are analyzed in terms of their ability to accurately reflect voter preference. The single nontransferable vote (SNTV is also included in the comparison as a benchmark. We construct a model of voting equilibria with a candidate who is least preferred by voters in the sense that replacing the least-preferred candidate in the set of winners with any loser is Pareto improving, and our focus is on whether the least-preferred candidate wins under each electoral system. We demonstrate that the least-preferred candidate never wins under the SNTV, but can win under open-list PR, although this is less likely than winning under closed-list PR.

  18. Consequences of winning: the role of gambling outcomes in the development of irrational beliefs.

    Science.gov (United States)

    Monaghan, Sally; Blaszczynski, Alex; Nower, Lia

    2009-01-01

    The development and maintenance of gambling and problem gambling with its corresponding irrational beliefs may be fundamentally linked to patterns of wins and losses during electronic gaming machine (EGM) play. The current study investigated the extent to which irrational thoughts and erroneous perceptions of chance differed based on individual wins or losses. Undergraduate students (n = 45) completed questionnaires assessing irrational beliefs and perceptions of chance prior to and following EGM play with credits rather than money. It was found that players who lost reported a significantly greater decrease in irrational thoughts and erroneous perceptions of chance and significantly fewer superstitious beliefs than winning players following play. Future studies are needed to further investigate the relationship of winning to cognitive distortions to guide education and interventions.

  19. Combined Joint Task Force-Horn of Africa: Winning the War on Terror with Information Engagement

    National Research Council Canada - National Science Library

    Garcia, Michelle M

    2007-01-01

    ...) to win the Global War on Terrorism (GWOT) in the Horn of Africa. Because of the mission, the resources available to the task force, and the nature of the conflict, the command chose a COA that uses Information Operations (IO...

  20. Contribution of fronto-striatal regions to emotional valence and repetition under cognitive conflict.

    Science.gov (United States)

    Chun, Ji-Won; Park, Hae-Jeong; Kim, Dai Jin; Kim, Eosu; Kim, Jae-Jin

    2017-07-01

    Conflict processing mediated by fronto-striatal regions may be influenced by emotional properties of stimuli. This study aimed to examine the effects of emotion repetition on cognitive control in a conflict-provoking situation. Twenty-one healthy subjects were scanned using functional magnetic resonance imaging while performing a sequential cognitive conflict task composed of emotional stimuli. The regional effects were analyzed according to the repetition or non-repetition of cognitive congruency and emotional valence between the preceding and current trials. Post-incongruence interference in error rate and reaction time was significantly smaller than post-congruence interference, particularly under repeated positive and non-repeated positive, respectively, and post-incongruence interference, compared to post-congruence interference, increased activity in the ACC, DLPFC, and striatum. ACC and DLPFC activities were significantly correlated with error rate or reaction time in some conditions, and fronto-striatal connections were related to the conflict processing heightened by negative emotion. These findings suggest that the repetition of emotional stimuli adaptively regulates cognitive control and the fronto-striatal circuit may engage in the conflict adaptation process induced by emotion repetition. Both repetition enhancement and repetition suppression of prefrontal activity may underlie the relationship between emotion and conflict adaptation. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Reduced amygdala and ventral striatal activity to happy faces in PTSD is associated with emotional numbing.

    Directory of Open Access Journals (Sweden)

    Kim L Felmingham

    Full Text Available There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1 individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2 that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.

  2. Beyond Neuronal Activity Markers: Select Immediate Early Genes in Striatal Neuron Subtypes Functionally Mediate Psychostimulant Addiction

    Directory of Open Access Journals (Sweden)

    Ramesh Chandra

    2017-06-01

    Full Text Available Immediate early genes (IEGs were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected. Nonetheless, there is a subset of research that investigates the functional role of IEGs in molecular, cellular and behavioral alterations by psychostimulants through striatal medium spiny neuron (MSN subtypes, the two projection neuron subtypes in striatum. This review article will address and highlight the studies that provide a functional mechanism by which IEGs mediate psychostimulant molecular, cellular and behavioral plasticity through MSN subtypes. Insight into the functional role of IEGs in striatal MSN subtypes could provide improved understanding into addiction and neuropsychiatric diseases affecting striatum, such as affective disorders and compulsive disorders characterized by dysfunctional motivation and habitual behavior.

  3. Dermatoglyphic asymmetries and fronto-striatal dysfunction in young-adults reporting non-clinical psychosis

    Science.gov (United States)

    Mittal, Vijay A.; Dean, Derek J.; Pelletier, Andrea

    2012-01-01

    Objective Growing evidence indicates that non-clinical psychotic-like experiences occur in otherwise healthy individuals, suggesting that psychosis may occur on a continuum. However, little is know about how the diathesis for formal psychosis maps on to individuals at the non-clinical side of this continuum. Our current understanding of the pathophysiology of schizophrenia implicates certain key factors such as early developmental abnormalities and fronto-striatal dysfunction. To date, no studies have examined these core factors in the context of non-clinical psychosis. Method A total of 221 young adults were assessed for distressing attenuated positive symptoms (DAPS), dermatoglyphic asymmetries (a marker of early developmental insult), and procedural memory (a proxy for fronto-striatal function). Results Participants reporting DAPS (n=16; 7.2%) and no-DAPS (n=205; 92.7%) were split into two groups. The DAPS group showed significantly elevated depression, elevated dermatoglyphic asymmetries, and a pattern of procedural learning consistent with other studies with formally psychotic patients. Conclusion The results indicate that the non-clinical side of the psychosis continuum also shares key vulnerability factors implicated in schizophrenia, suggesting that both early developmental disruption and abnormalities in fronto-striatal function are core aspects underlying the disorder. PMID:22519833

  4. Dermatoglyphic asymmetries and fronto-striatal dysfunction in young adults reporting non-clinical psychosis.

    Science.gov (United States)

    Mittal, V A; Dean, D J; Pelletier, A

    2012-10-01

    Growing evidence indicates that non-clinical psychotic-like experiences occur in otherwise healthy individuals, suggesting that psychosis may occur on a continuum. However, little is known about how the diathesis for formal psychosis maps on to individuals at the non-clinical side of this continuum. Our current understanding of the pathophysiology of schizophrenia implicates certain key factors such as early developmental abnormalities and fronto-striatal dysfunction. To date, no studies have examined these core factors in the context of non-clinical psychosis. A total of 221 young adults were assessed for distressing attenuated positive symptoms (DAPS), dermatoglyphic asymmetries (a marker of early developmental insult), and procedural memory (a proxy for fronto-striatal function). Participants reporting DAPS (n = 16; 7.2%) and no-DAPS (n = 205; 92.7%) were split into two groups. The DAPS group showed significantly elevated depression, elevated dermatoglyphic asymmetries, and a pattern of procedural learning consistent with other studies with formally psychotic patients. The results indicate that the non-clinical side of the psychosis continuum also shares key vulnerability factors implicated in schizophrenia, suggesting that both early developmental disruption and abnormalities in fronto-striatal function are core aspects underlying the disorder. © 2012 John Wiley & Sons A/S.

  5. A negative relationship between ventral striatal loss anticipation response and impulsivity in borderline personality disorder.

    Science.gov (United States)

    Herbort, Maike C; Soch, Joram; Wüstenberg, Torsten; Krauel, Kerstin; Pujara, Maia; Koenigs, Michael; Gallinat, Jürgen; Walter, Henrik; Roepke, Stefan; Schott, Björn H

    2016-01-01

    Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BPD patients and 23 age-matched female healthy controls using functional magnetic resonance imaging (fMRI). Participants performed a delayed monetary incentive task in which three categories of objects predicted a potential gain, loss, or neutral outcome. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11). Compared to healthy controls, BPD patients exhibited significantly reduced fMRI responses of the ventral striatum/nucleus accumbens (VS/NAcc) to both reward-predicting and loss-predicting cues. BIS-11 scores showed a significant positive correlation with the VS/NAcc reward anticipation responses in healthy controls, and this correlation, while also nominally positive, failed to reach significance in BPD patients. BPD patients, on the other hand, exhibited a significantly negative correlation between ventral striatal loss anticipation responses and BIS-11 scores, whereas this correlation was significantly positive in healthy controls. Our results suggest that patients with BPD show attenuated anticipation responses in the VS/NAcc and, furthermore, that higher impulsivity in BPD patients might be related to impaired prediction of aversive outcomes.

  6. Disrupted functional connectivity of striatal sub-regions in Bell's palsy patients

    Directory of Open Access Journals (Sweden)

    Wenwen Song

    2017-01-01

    Full Text Available The striatum plays an important role in controlling motor function in humans, and its degeneration has the ability to cause severe motor disorders. More specifically, previous studies have demonstrated a disruption in the connectivity of the cortico-striatal loop in patients suffering from motor disorders caused by dopamine dysregulation, such as Parkinson's disease. However, little is known about striatal functional connectivity in patients with motor dysfunction not caused by dopamine dysregulation. In this study, we used early-state Bell's palsy (BP patients (within 14 days of onset to investigate how functional connectivity between the striatum and motor cortex is affected by peripheral nerve injury in which the dopamine system remains fully functional. We found a significant increase in the connectivity between the contralateral putamen, and the ipsilateral primary sensory (S1 and motor cortex (M1 in BP patients compared to healthy controls. We also found increased connectivity between the ventral striatum and supplementary motor area (SMA, and the dorsal caudate and medial prefrontal lobe in BP patients compared to healthy controls. Our results demonstrate that the entirety of the striatum is affected following acute peripheral nerve injury, and suggests that this disrupted striatal functional connectivity may reflect a compensatory mechanism for the sensory-motor mismatch caused by BP.

  7. Postural & striatal deformities in Parkinson`s disease: Are these rare?

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2016-01-01

    Full Text Available Parkinson`s disease (PD is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.

  8. In Vitro Manganese Exposure Disrupts MAPK Signaling Pathways in Striatal and Hippocampal Slices from Immature Rats

    Directory of Open Access Journals (Sweden)

    Tanara Vieira Peres

    2013-01-01

    Full Text Available The molecular mechanisms mediating manganese (Mn-induced neurotoxicity, particularly in the immature central nervous system, have yet to be completely understood. In this study, we investigated whether mitogen-activated protein kinases (MAPKs and tyrosine hydroxylase (TH could represent potential targets of Mn in striatal and hippocampal slices obtained from immature rats (14 days old. The aim of this study was to evaluate if the MAPK pathways are modulated after subtoxic Mn exposure, which do not significantly affect cell viability. The concentrations of manganese chloride (MnCl2; 10–1,000 μM caused no change in cell viability in slices exposed for 3 or 6 hours. However, Mn exposure significantly increased extracellular signal-regulated kinase (ERK 1/2, as well as c-Jun N-terminal kinase (JNK 1/2/3 phosphorylation at both 3 and 6 hours incubations, in both brain structures. Furthermore, Mn exposure did not change the total content or phosphorylation of TH at the serine 40 site in striatal slices. Thus, Mn at concentrations that do not disrupt cell viability causes activation of MAPKs (ERK1/2 and JNK1/2/3 in immature hippocampal and striatal slices. These findings suggest that altered intracellular MAPKs signaling pathways may represent an early event concerning the effects of Mn in the immature brain.

  9. A negative relationship between ventral striatal loss anticipation response and impulsivity in borderline personality disorder

    Directory of Open Access Journals (Sweden)

    Maike C. Herbort

    2016-01-01

    Full Text Available Patients with borderline personality disorder (BPD frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BPD patients and 23 age-matched female healthy controls using functional magnetic resonance imaging (fMRI. Participants performed a delayed monetary incentive task in which three categories of objects predicted a potential gain, loss, or neutral outcome. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11. Compared to healthy controls, BPD patients exhibited significantly reduced fMRI responses of the ventral striatum/nucleus accumbens (VS/NAcc to both reward-predicting and loss-predicting cues. BIS-11 scores showed a significant positive correlation with the VS/NAcc reward anticipation responses in healthy controls, and this correlation, while also nominally positive, failed to reach significance in BPD patients. BPD patients, on the other hand, exhibited a significantly negative correlation between ventral striatal loss anticipation responses and BIS-11 scores, whereas this correlation was significantly positive in healthy controls. Our results suggest that patients with BPD show attenuated anticipation responses in the VS/NAcc and, furthermore, that higher impulsivity in BPD patients might be related to impaired prediction of aversive outcomes.

  10. Phasic Dopamine Modifies Sensory-Driven Output of Striatal Neurons through Synaptic Plasticity.

    Science.gov (United States)

    Wieland, Sebastian; Schindler, Sebastian; Huber, Cathrin; Köhr, Georg; Oswald, Manfred J; Kelsch, Wolfgang

    2015-07-08

    Animals are facing a complex sensory world in which only few stimuli are relevant to guide behavior. Value has to be assigned to relevant stimuli such as odors to select them over concurring information. Phasic dopamine is involved in the value assignment to stimuli in the ventral striatum. The underlying cellular mechanisms are incompletely understood. In striatal projection neurons of the ventral striatum in adult mice, we therefore examined the features and dynamics of phasic dopamine-induced synaptic plasticity and how this plasticity may modify the striatal output. Phasic dopamine is predicted to tag inputs that occur in temporal proximity. Indeed, we observed D1 receptor-dependent synaptic potentiation only when odor-like bursts and optogenetically evoked phasic dopamine release were paired within a time window of synaptic potentiation persisted after the phasic dopamine signal had ceased, but gradually reversed when odor-like bursts continued to be presented. The synaptic plasticity depended on the sensory input rate and was input specific. Importantly, synaptic plasticity amplified the firing response to a given olfactory input as the dendritic integration and the firing threshold remained unchanged during synaptic potentiation. Thus, phasic dopamine-induced synaptic plasticity can change information transfer through dynamic increases of the output of striatal projection neurons to specific sensory inputs. This plasticity may provide a neural substrate for dynamic value assignment in the striatum. Copyright © 2015 the authors 0270-6474/15/359946-11$15.00/0.

  11. Winning strategies for pseudo-telepathy games using single non-local box

    International Nuclear Information System (INIS)

    Kunkri, S.; Kar, G.; Ghosh, S.; Roy, A.

    2006-12-01

    Using a single NL-box, a winning strategy is given for the impossible colouring pseudo-telepathy game for the set of vectors having Kochen-Specker property in four dimension. A sufficient condition given regarding the structure of the impossible colouring pseudo-telepathy game for general d-dimension. A winning strategy for this game is then described with single use of NL-box. (author)

  12. Improving working equine welfare in 'hard-win' situations, where gains are difficult, expensive or marginal.

    Science.gov (United States)

    Pritchard, Joy; Upjohn, Melissa; Hirson, Tamsin

    2018-01-01

    Brooke is a non-government organisation with working equine welfare programmes across Africa, Asia and Latin America. In 2014, staff from ten country programmes were asked to identify 'no-win' situations (subsequently reframed as 'hard-wins')-where improving equine welfare is proving difficult, expensive and/or marginal-in order to inform strategic decisions on how to approach, manage and mitigate for such situations. The Delphi-type consultation process had three phases. Round 1 posed five questions in the form of a workshop, survey and semi-structured interviews. Round 2 re-presented key themes and sense-checked initial conclusions. Round 3 reviewed the nature and prevalence of hard-win situations at an international meeting of all participants. Reasons given for hard-win situations included: no economic or social benefit from caring for working animals; poor resource availability; lack of empathy for working equids or their owners among wider stakeholders; deep-seated social issues, such as addiction or illegal working; areas with a high animal turnover or migratory human population; lack of community cooperation or cohesion; unsafe areas where welfare interventions cannot be adequately supported. Participants estimated the prevalence of hard-win situations as 40-70% of their work. They suggested some current ways of working that may be contributing to the problem, and opportunities to tackle hard-wins more effectively. Respondents agreed that if equine welfare improvements are to span generations of animals, interventions cannot rely on relatively simple, technical knowledge-transfer strategies and quick-wins alone. Programmes need to be more flexible and iterative and less risk-averse in their approaches to embedding good equine welfare practices in all relevant actors. Consultation recommendations informed development of Brooke's new global strategy, a revised organisational structure and redefinition of roles and responsibilities to streamline ways to

  13. CERN Club Football wins 40 year old tradition cup

    CERN Multimedia

    Dave Underhill

    2016-01-01

    Already two weeks since the CERN football team, representing the Dave Underhill XI in the annual match with the Geneva Scottish Football Club, made a late, late rally to win the Jean Pierre Fillettaz Trophy. They started well with some good passing movements, but the Scots were also playing well and began to take control towards the end of the first half. Then, following a series of poor finishing and good goalkeeping by the CERN keeper, they finally found the back of the net, and the lads in white trooped off for well-earned oranges and water, just 1-0 down at half time. The second half was again evenly matched, but while we were not making the goal chances the Scots were squandering theirs. THEN with just 10 minutes to go a sudden resurgence of energy and aggression, the CERNites made the chances which counted, and in the space 5 minutes turned the score around and were happy to hear the final whistle and celebrate a famous 2-1 victory. Victory and commiserations were celebrated in the "Club Ho...

  14. Proceedings of the WIN-Global 2008 conference

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2008-07-01

    WiN-France hosted the 16. WIN-Global conference May 26-30, 2008, in Marseille, France. The conference was attended by over 150 delegates, representing 30 countries. Canadian participants, from many diverse backgrounds, attended the annual conference from AECL, Bruce Power, CNSC, NB Power and OPG. The theme: Maintaining Key Competencies, Arising Key Competencies for Nuclear Energy: A Challenge and Opportunity for Diversity Development, emphasized the challenges ahead in providing a skilled workforce for the nuclear renaissance, as new build projects and a vast number of retirements are expected around the world within the next 5 years. The conference addressed such questions as 'How will nuclear, attract, develop and retain staff?' A technical tour of Marcoule invited conference attendees to visit one of: Atalante, a high level nuclear chemistry laboratory; Phenix, a fast breeding research reactor; or AVM, a vitrification plant. A subsequent technical tour visited Cadarache providing the opportunity to view ITER, the international fusion research project.

  15. Autoradiography: (/sup 125/I)SCH 23982 binds with picomolar affinity to D1 sites on striatonigral neurons

    Energy Technology Data Exchange (ETDEWEB)

    Altar, C.A.; Marien, M.R.

    1986-03-01

    SCH 23390 is selective D1 antagonist. The authors show for the first time, with iodinated SCH 23390, (/sup 125/I)SCH 23982, D1 binding sites on striatonigral neurons. Rat brain sections were covered for 1 hr by a pH 7.6 TRIS buffer containing 2-770 pM (/sup 125/I)SCH 23982, rinsed 2 min at 4 /sup 0/C, dried, and exposed to film for 18 hr. (/sup 125/I)SCH 23982 was displaced by D1 (SCH 23390; IC50= 200 pM; cis-flupenthixol, 10 nM; SKF 38393, 90 nM) but not D2 (sulpiride, LY171555) ligands. Intermediate D1 binding was found in the internal capsule and entopeduncular nucleus. Striatal quinolinate (100 nmol) decreased nigral and striatal D1 binding. Intranigral 6-hydroxydopamine (6 ..mu..g) that destroyed > 90% of nigrostriatal dopamine neurons did not alter nigral or striatal D1 binding. Thus, (/sup 125/I)SCH 23982 labels with pM affinity D1 sites that reside on striatonigral neurons.

  16. International land deals, local people's livelihood, and environment nexus (How to create win-win land deals in Ethiopia?)

    Science.gov (United States)

    Teklemariam Gebremeskel, Dereje; Witlox, Frank; Azadi, Hossein; Haile, Mitiku; Nyssen, Jan

    2013-04-01

    Following the global raise in demand for food and biofuel production, transnational companies are acquiring large scale agricultural land in developing countries such as Ethiopia. Considering land as one of the factors to be outsourced for development, the government of Ethiopia is supplying millions of hectares of land to transnational companies in the form of longterm lease. Many of the companies which engage in large scale land acquisition are of Indian, Chinese, Ethiopian diaspora, German, Malaysian, Italian, British, Dutch, Turkish, and Saudi-Arabian origin. The boom in the acquisition of farm land in the country has sparked an all-rounded debate among civil society groups, international institutions, nongovernmental organizations and independent development experts. The common reflections concerning the land deals in Ethiopia and elsewhere contain much rhetoric and hype which lack analysis of the real situation "on the ground" giving different connotations such as 'land grabbing', 'agricultural outsourcing', 'neo-colonialism', 'agrarian colonialism', and 'land underdevelopment'. However, deforestation, soil degradation, marginalization of local indigenous communities, and minimally unfair gains from investment by the host country are among the real points of concern arising out of the long term land lease contracts. Scientific evidence is lacking concerning the pragmatic impacts of large scale agricultural land acquisitions by transnational companies upon the natural environment (forest and land), local peoples' livelihood, and the contacting parties (the host country and the companies). The major objective of this study is to investigate the impacts in the context of Ethiopia, orienting to reinvent win-win land use models which constitute sustainable land use, local peoples' livelihood and the company-host country interests. To achieve this overall objective, the study employs a number of methods and methodologies constituting both qualitative and

  17. Capturing SCL and HR changes to win and loss events during gambling on electronic machines.

    Science.gov (United States)

    Wilkes, Benjamin L; Gonsalvez, Craig J; Blaszczynski, Alex

    2010-12-01

    The role of physiological arousal is central to theories about the onset and maintenance of gambling behaviours including problem gambling. The range of possibilities suggested include tonic underarousal and phasic abnormalities such as hypersensitivity to reward and/or reduced sensitivity to negative consequences associated with losses. Among the various types of gambling, electronic gambling machines (EGMs) are associated with the large majority of gambling related problems. The demonstration that physiological changes associated with rapidly occurring win and loss events during electronic gambling can be reliably captured is fundamental to further progress in the psychophysiology of gambling. The current study monitored electrodermal and cardiac activities of twenty-four healthy participants to event outcomes (losses, fake wins, small wins and big wins) during a task on a real EGM. The results demonstrated that it is possible to reliably capture the profile of physiological changes as they occurred in real time to the many different win and loss events during electronic gambling. Relative to baseline levels, win events produced significant increases in skin conductance levels, (but not in HR) whereas loss events produced no significant changes. The study has important applications for further experimental and clinical research. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. Faking or Convincing: Why Do Some Advertising Campaigns Win Creativity Awards?

    Directory of Open Access Journals (Sweden)

    Raoul V. Kübler

    2012-05-01

    Full Text Available Since the Sarbanes-Oxley Act was passed in 2002, it has become commonplace in the advertising industry to use creativity-award-show prizes instead of gross income figures to attract new customers. Therefore, achieving a top creativity ranking and winning creativity awards have become high priorities in the advertising industry. Agencies and marketers have always wondered what elements in the advertising creation process would lead to the winning of creativity awards. Although this debate has been dominated by pure speculation about the success of different routines, approaches and strategies in winning creativity awards, for the first time our study delivers an empirical insight into the key drivers of creativity award success. We investigate what strategies and which elements of an advertising campaign are truly likely to lead to winning the maximum number of creativity awards. Using a sample of 108 campaigns, we identify factors that influence campaign success at international advertising award shows. We identify innovativeness and the integration of multiple channels as the key drivers of creativity award success. In contrast to industry beliefs, meaningful or personally connecting approaches do not seem to generate a significant benefit in terms of winning creativity awards. Finally, our data suggest that the use of so-called “fake campaigns” to win more creativity awards does not prove to be effective.

  19. Morphological features of neurons containing calcium-binding proteins in the human striatum.

    Science.gov (United States)

    Prensa, L; Giménez-Amaya, J M; Parent, A

    1998-01-26

    An immunohistochemical approach was used to characterize the morphological phenotype of neurons containing the calcium-binding proteins calretinin (CR), parvalbumin (PV), or calbindin-D28k (CB) in the normal human striatum. The protein CR occurs in at least four morphologically distinct types of neurons. Apart from the numerous medium-sized aspiny interneurons and the less abundant giant aspiny interneurons, CR also labels some medium-sized spiny neurons morphologically identical to striatal projection neurons. This finding indicates that CR is not only confined to striatal interneurons but also may be involved in the function of certain projection neurons. Some small and peculiar bushy-like aspiny neurons also are enriched with CR. These neurons could correspond to the dwarf or neurogliform neurons first described by Ramón y Cajal (1911). Three types of PV-immunoreactive striatal neurons can be visualized in the human striatum: 1) the common medium-sized aspiny leptodendritic neurons, 2) some smaller and profusely arborized aspiny neurons, and 3) a few large and intensely stained neurons with conspicuously beaded and poorly branched dendrites. The protein CB labels virtually all medium-sized spiny projection neurons located in the striatal matrix but also identifies a small subset of large and more intensely immunostained aspiny neurons. The latter finding indicates that CB is not entirely confined to striatal projection neurons but also may play a role in local circuit neurons. These normative data should help our understanding of the chemical anatomy of the human striatum in both health and disease.

  20. Differential up-regulation of striatal dopamine transporter and α-synuclein by the pyrethroid insecticide permethrin

    International Nuclear Information System (INIS)

    Gillette, Jeffrey S.; Bloomquist, Jeffrey R.

    2003-01-01

    The effects of permethrin on striatal dopaminergic biomarkers were assessed in this study. Retired breeder male C57 B1/6 mice were given an ip dose of permethrin (0.1-200 mg/kg) at 7-day intervals, over a 2-week period (Days 0, 7, and 14). Animals were then sacrificed 1 day (t = 1), 14 days (t 14), or 28 days after the last treatment (t = 28). Dopamine transporter (DAT) protein as assayed by Western blotting was increased to 115% in the 0.8 mg/kg group over that of control mice at t = 1 (P 3 H]GBR 12935, used to assay DAT binding, followed the same trend as that for the Western blotting data for 0.8 and 1.5 mg/kg doses of permethrin over the 4 weeks posttreatment. At 200 mg/kg permethrin, DAT protein was unchanged vs controls (t = 1), but had significantly increased by t = 14 and continued to increase at t = 28, suggesting that the reduced dopamine transport at this dose was due to nerve terminal stress and that recovery had occurred. The protein α-synuclein was also significantly induced at the 1.5 mg/kg dose at t = 1; however, unlike DAT up-regulation, this effect had declined to control values by t 14. Maximal induction of α-synuclein protein occurred at a dose of 50 mg/kg permethrin. These data provide evidence that the pyrethroid class of insecticides can modulate the dopaminergic system at low doses, in a persistent manner, which may render neurons more vulnerable to toxicant injury

  1. A simple algorithm for subregional striatal uptake analysis with partial volume correction in dopaminergic PET imaging

    International Nuclear Information System (INIS)

    Lue Kunhan; Lin Hsinhon; Chuang Kehshih; Kao Chihhao, K.; Hsieh Hungjen; Liu Shuhsin

    2014-01-01

    In positron emission tomography (PET) of the dopaminergic system, quantitative measurements of nigrostriatal dopamine function are useful for differential diagnosis. A subregional analysis of striatal uptake enables the diagnostic performance to be more powerful. However, the partial volume effect (PVE) induces an underestimation of the true radioactivity concentration in small structures. This work proposes a simple algorithm for subregional analysis of striatal uptake with partial volume correction (PVC) in dopaminergic PET imaging. The PVC algorithm analyzes the separate striatal subregions and takes into account the PVE based on the recovery coefficient (RC). The RC is defined as the ratio of the PVE-uncorrected to PVE-corrected radioactivity concentration, and is derived from a combination of the traditional volume of interest (VOI) analysis and the large VOI technique. The clinical studies, comprising 11 patients with Parkinson's disease (PD) and 6 healthy subjects, were used to assess the impact of PVC on the quantitative measurements. Simulations on a numerical phantom that mimicked realistic healthy and neurodegenerative situations were used to evaluate the performance of the proposed PVC algorithm. In both the clinical and the simulation studies, the striatal-to-occipital ratio (SOR) values for the entire striatum and its subregions were calculated with and without PVC. In the clinical studies, the SOR values in each structure (caudate, anterior putamen, posterior putamen, putamen, and striatum) were significantly higher by using PVC in contrast to those without. Among the PD patients, the SOR values in each structure and quantitative disease severity ratings were shown to be significantly related only when PVC was used. For the simulation studies, the average absolute percentage error of the SOR estimates before and after PVC were 22.74% and 1.54% in the healthy situation, respectively; those in the neurodegenerative situation were 20.69% and 2

  2. Dopamine D(1) receptor-mediated control of striatal acetylcholine release by endogenous dopamine.

    Science.gov (United States)

    Acquas, E; Di Chiara, G

    1999-10-27

    The role of dopamine D(1) and D(2) receptors in the control of acetylcholine release in the dorsal striatum by endogenous dopamine was investigated by monitoring with microdialysis the effect of the separate or combined administration of the dopamine D(1) receptor antagonist, SCH 39166 ¿(-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride¿ (50 microg/kg subcutaneous (s.c.)), of the dopamine D(2)/D(3) receptor agonist, quinpirole (trans-(-)-4aR, 4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo-(3,4-g)-quinoline hydrochloride) (5 and 10 microg/kg s.c.), and of the D(3) receptor selective agonist, PD 128,907 [S(+)-(4aR,10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin -9-ol hydrochloride] (50 microg/kg s.c.), on in vivo dopamine and acetylcholine release. Microdialysis was performed with a Ringer containing low concentrations (0.01 microM) of the acetylcholinesterase inhibitor, neostigmine. Quinpirole (10 microg/kg s.c.) decreased striatal dopamine and acetylcholine release. Administration of PD 128,907 (50 microg/kg) decreased dopamine but failed to affect acetylcholine release. SCH 39166 (50 microg/kg s.c.) stimulated dopamine release and reduced acetylcholine release. Pretreatment with quinpirole reduced (5 microg/kg s.c.) or completely prevented (10 microg/kg s.c.) the stimulation of dopamine release elicited by SCH 39166 (50 microg/kg s.c.); on the other hand, pretreatment with quinpirole (5 and 10 microg/kg) potentiated the reduction of striatal acetylcholine release induced by SCH 39166 (50 microg/kg s.c.). Similarly, pretreatment with PD 128,907 (50 microg/kg) which prevented the increase of dopamine release induced by SCH 39166 (50 microg/kg), potentiated the reduction of striatal acetylcholine transmission elicited by SCH 39166. Thus, pretreatment with low doses of quinpirole or PD 128,907 influences in opposite manner the effect of SCH 39166 on striatal dopamine and

  3. A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations.

    Science.gov (United States)

    Sharott, Andrew; Vinciati, Federica; Nakamura, Kouichi C; Magill, Peter J

    2017-10-11

    Classical schemes of basal ganglia organization posit that parkinsonian movement difficulties presenting after striatal dopamine depletion stem from the disproportionate firing rates of spiny projection neurons (SPNs) therein. There remains, however, a pressing need to elucidate striatal SPN firing in the context of the synchronized network oscillations that are abnormally exaggerated in cortical-basal ganglia circuits in parkinsonism. To address this, we recorded unit activities in the dorsal striatum of dopamine-intact and dopamine-depleted rats during two brain states, respectively defined by cortical slow-wave activity (SWA) and activation. Dopamine depletion escalated striatal net output but had contrasting effects on "direct pathway" SPNs (dSPNs) and "indirect pathway" SPNs (iSPNs); their firing rates became imbalanced, and they disparately engaged in network oscillations. Disturbed striatal activity dynamics relating to the slow (∼1 Hz) oscillations prevalent during SWA partly generalized to the exaggerated beta-frequency (15-30 Hz) oscillations arising during cortical activation. In both cases, SPNs exhibited higher incidences of phase-locked firing to ongoing cortical oscillations, and SPN ensembles showed higher levels of rhythmic correlated firing, after dopamine depletion. Importantly, in dopamine-depleted striatum, a widespread population of iSPNs, which often displayed excessive firing rates and aberrant phase-locked firing to cortical beta oscillations, preferentially and excessively synchronized their firing at beta frequencies. Conversely, dSPNs were neither hyperactive nor synchronized to a large extent during cortical activation. These data collectively demonstrate a cell type-selective entrainment of SPN firing to parkinsonian beta oscillations. We conclude that a population of overactive, excessively synchronized iSPNs could orchestrate these pathological rhythms in basal ganglia circuits. SIGNIFICANCE STATEMENT Chronic depletion of dopamine

  4. Striatal hypometabolism in premanifest and manifest Huntington's disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Mora, Diego Alfonso; Camacho, Valle; Fernandez, Alejandro; Montes, Alberto; Carrio, Ignasi [Autonomous University of Barcelona, Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Perez-Perez, Jesus; Martinez-Horta, Sauel; Kulisevsky, Jaime [Autonomous University of Barcelona, Movement Disorders Unit, Neurology Department, Hospital Sant Pau, Barcelona (Spain); Sampedro, Frederic [University of Barcelona, Barcelona (Spain); Lozano-Martinez, Gloria Andrea; Gomez-Anson, Beatriz [Autonomous University of Barcelona, Neuroradiology, Radiology Department, Hospital Sant Pau, Barcelona (Spain)

    2016-11-15

    To assess metabolic changes in cerebral {sup 18}F-FDG PET/CT in premanifest and manifest Huntington's disease (HD) subjects compared to a control group and to correlate {sup 18}F-FDG uptake patterns with different disease stages. Thirty-three gene-expanded carriers (Eight males; mean age: 43 y/o; CAG > 39) were prospectively included. Based on the Unified Huntington's Disease Rating Scale Total Motor Score and the Total Functional Capacity, subjects were classified as premanifest (preHD = 15) and manifest (mHD = 18). Estimated time disease-onset was calculated using the Langbehn formula, which allowed classifying preHD as far-to (preHD-A) and close-to (PreHD-B) disease-onset. Eighteen properly matched participants were included as a control group (CG). All subjects underwent brain {sup 18}F-FDG PET/CT and MRI. {sup 18}F-FDG PET/CT were initially assessed by two nuclear medicine physicians identifying qualitative metabolic changes in the striatum. Quantitative analysis was performed using SPM8 with gray matter atrophy correction using the BPM toolbox. Visual analysis showed a marked striatal hypometabolism in mHD. A normal striatal distribution of {sup 18}F-FDG uptake was observed for most of the preHD subjects. Quantitative analysis showed a significant striatal hypometabolism in mHD subjects compared to CG (p < 0.001 uncorrected, k = 50 voxels). In both preHD groups we observed a significant striatal hypometabolism with respect to CG (p < 0.001 uncorrected, k = 50 voxels). In mHD subjects we observed a significant striatal hypometabolism with respect to both preHD groups (p < 0.001 uncorrected, k = 50 voxels). {sup 18}F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. {sup 18}F-FDG PET/CT appears as a

  5. Serotonin 1B Receptor Binding Is Associated With Trait Anger and Level of Psychopathy in Violent Offenders

    DEFF Research Database (Denmark)

    da Cunha-Bang, Sofi; Hjordt, Liv Vadskjaer; Perfalk, Erik

    2017-01-01

    anger (difference in slopes, pcorrected = .04). In the violent offender group, striatal 5-HT1BR binding was positively correlated with self-reported trait anger (p = .0004), trait psychopathy (p = .008), and level of psychopathy according to the Psychopathy Checklist-Revised (p = .02). We found no group...... differences in 5-HT1BR binding. CONCLUSIONS: Our data demonstrate for the first time in humans a specific involvement of 5-HT1BR binding in anger and psychopathy. 5-HT1BRs putatively represent a molecular target for development of pharmacologic antiaggressive treatments....

  6. Not quite a win-win: the corporate agenda of the stay at work/return to work project.

    Science.gov (United States)

    Lax, Michael

    2015-05-01

    The idea that efforts are necessary to transform the dominant framework of workplace safety and health in the United States, from one of compensation and disability to one of stay at work/return to work (SAW/RTW) for workers injured or made ill on the job, has become increasingly widespread. SAW/RTW advocates argue that everyone "wins" when unnecessary disability is reduced. Toward this end, advocates have put forward a program and implemented a strategy with strong proponents among a coalition of corporate-connected professionals. The seemingly obvious conclusions of their arguments bear closer critical scrutiny, however. Addressing key questions-why injured workers do not SAW/RTW, who the coalition of SAW/RTW proponents includes, and what the coalition proposes-reveals that the SAW/RTW approach mainly benefits employers and the corporate-connected advocates. These assertions are detailed, and principles of an alternative approach that will serve the needs of injured workers are outlined. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  7. GDNF control of the glutamatergic cortico-striatal pathway requires tonic activation of adenosine A2A Receptors

    Science.gov (United States)

    Gomes, Catarina A.R.V.; Simões, Patrícia F.; Canas, Paula M.; Quiroz, César; Sebastião, Ana M.; Ferré, Sergi; Cunha, Rodrigo A.; Ribeiro, Joaquim A.

    2009-01-01

    Glial cell line-derived neurotrophic factor (GDNF) affords neuroprotection in Parkinson’s disease in accordance with its ability to bolster nigrostriatal innervation. We previously found that GDNF facilitates dopamine release in a manner dependent on adenosine A2A receptor activation. Since motor dysfunction also involves modifications of striatal glutamatergic innervation, we now tested if GDNF and its receptor system, Ret (rearranged during transfection) and GFRα1 (GDNF family receptor alpha 1) controlled the cortico-striatal glutamatergic pathway in an A2A receptor-dependent manner. GDNF (10 ng/ml) enhanced (by ≈13%) glutamate release from rat striatal nerve endings, an effect potentiated (up to ≈ 30%) by the A2A receptor agonist CGS 21680 (10 nM) and prevented by the A2A receptor antagonist, SCH 58261 (50 nM). Triple immunocytochemical studies revealed that Ret and GFRα1 were located in 50% of rat striatal glutamatergic terminals (immunopositive for vesicular glutamate transporters-1/2), where they were found to be co-located with A2A receptors. Activation of the glutamatergic system upon in vivo electrical stimulation of the rat cortico-striatal input induced striatal Ret phosphoprylation that was prevented by pre-treatment with the A2A receptor antagonist, MSX-3 (3 mg/kg). The results provide the first functional and morphological evidence that GDNF controls cortico-striatal glutamatergic pathways in a manner largely dependent on the co-activation of adenosine A2A receptors. PMID:19141075

  8. Growth hormone (GH) is a survival rather than a proliferative factor for embryonic striatal neural precursor cells.

    Science.gov (United States)

    Regalado-Santiago, Citlalli; López-Meraz, María Leonor; Santiago-García, Juan; Fernández-Pomares, Cynthia; Juárez-Aguilar, Enrique

    2013-10-01

    A possible role of GH during central nervous system (CNS) development has been suggested by the presence of this hormone and its receptor in brain areas before its production by the pituitary gland. Although several effects have been reported for GH, the specific role of this hormone during CNS development remains unclear. Here, we examined the effect of GH on proliferation, survival and neurosphere formation in primary cultures of striatal tissue from 14-day-old (E14) mouse embryos. GH receptor gene expression was confirmed by RT-PCR. Primary cultures of embryonic striatal cells were treated with different doses of GH in serum free media, then the number of neurospheres was determined. To examine the GH effect on proliferation and survival of the striatal primary cultures, bromodeoxyuridine (BrdU) and TUNEL immunoreactivity was conducted. In the presence of the epidermal growth factor (EGF), GH increased the formation of neurospheres, with a maximal response at 10 ng/ml, higher doses were inhibitory. In absence of EGF, GH failed to stimulate neurosphere formation. Proliferation rate in the primary striatal cultures was inhibited by 24 or 48 h incubation with GH. However, in the absence of EGF, GH increased BrdU incorporation. GH treatment decreases the rate of apoptosis of nestin and GFAP positive cells in the primary striatal cultures, enhancing neurosphere formation. Our in vitro data demonstrate that GH plays a survival role on the original population of embryonic striatal cells, improving Neural Precursor Cells (NPCs) expansion. We suggest that this GH action could be predominant during striatal neurodevelopment. © 2013.

  9. Ascorbic acid and striatal transport of (/sup 3/H)1-methyl-4-phenylpyridine (MPP/sup +/) and (/sup 3/H)dopamine

    Energy Technology Data Exchange (ETDEWEB)

    Debler, E.A.; Hashim, A.; Lajtha, A.; Sershen, H.

    1988-01-01

    The inhibition of uptake of (/sup 3/H)dopamine and (/sup 3/H)1-methyl-4-phenylpyridine (MPP/sup +/) was examined in mouse striatal synaptosomal preparations. Kinetic analysis indicated that ascorbic acid is a noncompetitive inhibitor of (/sup 3/H)MPP/sup +/ uptake. No inhibition of (/sup 3/H)dopamine uptake is observed. The dopamine uptake blockers, GBR-12909, cocaine, and mazindol strongly inhibit (IC/sub 50/ < 1 ..mu..M) both (/sup 3/H)dopamine and (/sup 3/H)MPP/sup +/ transport. Nicotine, its metabolites, and other tobacco alkaloids are weak inhibitors except 4-phenylpyridine and lobeline, which are moderate inhibitors of both (/sup 3/H)dopamine and (/sup 3/H)MPP/sup +/ uptake. These similarities in potencies are in agreement with the suggestion that (/sup 3/H)MPP/sup +/ and (/sup 3/H) are transported by the same carrier. The differences observed in the alteration of dopaminergic transport and mazindol binding by ascorbic acid suggest that ascorbic acid's effects on (/sup 3/H)MPP/sup +/ transport are related to translocation and/or dissociation processes occurring subsequent to the initial binding event.

  10. The Perceptions of Administrators from Quality Award-Winning School Districts and a Comparison of Student Academic Achievement in Quality Award-Winning Districts

    Science.gov (United States)

    Jauch, Kevin

    2010-01-01

    This research project served two main purposes. The first was to uncover the perceptions of district administrators from Quality award-winning school districts in regard to the use of the Malcolm Baldrige National Quality Award program as a management framework. This was accomplished by using the Interstate School Leaders Licensure Consortium's…

  11. DIFFERENCES IN GAME STATISTICS BETWEEN WINNING AND LOSING RUGBY TEAMS IN THE SIX NATIONS TOURNAMENT

    Directory of Open Access Journals (Sweden)

    José M. Palao

    2009-12-01

    Full Text Available The objective of the present study was to analyze the differences in rugby game statistics between winning and losing teams. The data from 58 games of round robin play from the Six Nations tournament from the 2003-2006 seasons were analyzed. The groups of variables studied were: number of points scored, way in which the points were scored; way teams obtained the ball and how the team used it; and technical and tactical aspects of the game. A univariate (t-test and multivariate (discriminant analysis of data was done. Winning teams had average values that were significantly higher in points scored, conversions, successful drops, mauls won, line breaks, possessions kicked, tackles completed, and turnovers won. Losing teams had significantly higher averages for the variables scrums lost and line-outs lost. The results showed that: a in the phases of obtaining the ball and more specifically in scrummage and line-out, winning teams lose fewer balls than losing teams (winning teams have an efficacy of 90% in both actions; b the winning team tends to play more with their feet when they obtain the ball, to utilize the maul as a way of attacking, and to break the defensive line more often than the losing team does; and c On defence, winning teams recovered more balls and completed more tackles than losing teams, and the percentage of tackles completed by winning teams was 94%. The value presented could be used as a reference for practice and competition in peak performance teams

  12. Improvement of information on the nuclear energy health effects, the aim of win Slovakia

    International Nuclear Information System (INIS)

    Petrasova, M.; Nikodemova, D.

    1998-01-01

    International organisation WIN Global and national organisation WIN Slovakia which as a section of Slovak Nuclear Society, offer unique opportunities for the improvement of radiation risk communication. WIN Global was established in 1993 and currently has about 600 members in 39 countries. WIN Slovakia was established in the end of 1997 and has 20 members. WIN Slovakia is the association of women working professionally in the fields of nuclear energy and application of radiation and willing to devote time to public information. Members of WIN Slovakia all have one thing in common: They want the general public to have a better understanding of nuclear and radiation matter. The members of WIN Slovakia would like and plane to make presentations, discuss and give information material on subjects as: energy and sustainable development; radiation, radioactivity, and health effects; medical applications, radiation protection; nuclear energy, uranium mining; nuclear power plants and their safety; radioactive waste; nuclear and environment; natural radiation, radon. In 1996-1997 a comparative risk perception study was carried out in Slovak Republic. Real data were collected through the administration of a questionnaires distributed among a group of 14-17 years old children (N 1 = 308) and teenagers (N 2 = 150). The list of 44 items covered a wide range of risks and hazards, including risks from technology (nuclear power plants, water-dams etc.) pollution (air-, water-, soil, waste management) nature (floods, fire, etc.), life style (smoking, drugs, alcohol abuse) and society (crime, conflicts, war, terror etc.). The questionnaire contains the questions about the sources of risk information. The topic of the study was the self assessment of the knowledge on particular risks too. The results were summarised

  13. Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC mouse

    Directory of Open Access Journals (Sweden)

    Belknap John

    2010-10-01

    Full Text Available Abstract Background The current study focused on the extent genetic diversity within a species (Mus musculus affects gene co-expression network structure. To examine this issue, we have created a new mouse resource, a heterogeneous stock (HS formed from the same eight inbred strains that have been used to create the collaborative cross (CC. The eight inbred strains capture > 90% of the genetic diversity available within the species. For contrast with the HS-CC, a C57BL/6J (B6 × DBA/2J (D2 F2 intercross and the HS4, derived from crossing the B6, D2, BALB/cJ and LP/J strains, were used. Brain (striatum gene expression data were obtained using the Illumina Mouse WG 6.1 array, and the data sets were interrogated using a weighted gene co-expression network analysis (WGCNA. Results Genes reliably detected as expressed were similar in all three data sets as was the variability of expression. As measured by the WGCNA, the modular structure of the transcriptome networks was also preserved both on the basis of module assignment and from the perspective of the topological overlap maps. Details of the HS-CC gene modules are provided; essentially identical results were obtained for the HS4 and F2 modules. Gene ontology annotation of the modules revealed a significant overrepresentation in some modules for neuronal processes, e.g., central nervous system development. Integration with known protein-protein interactions data indicated significant enrichment among co-expressed genes. We also noted significant overlap with markers of central nervous system cell types (neurons, oligodendrocytes and astrocytes. Using the Allen Brain Atlas, we found evidence of spatial co-localization within the striatum for several modules. Finally, for some modules it was possible to detect an enrichment of transcription binding sites. The binding site for Wt1, which is associated with neurodegeneration, was the most significantly overrepresented. Conclusions Despite the marked

  14. Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC) mouse.

    Science.gov (United States)

    Iancu, Ovidiu D; Darakjian, Priscila; Walter, Nicole A R; Malmanger, Barry; Oberbeck, Denesa; Belknap, John; McWeeney, Shannon; Hitzemann, Robert

    2010-10-19

    The current study focused on the extent genetic diversity within a species (Mus musculus) affects gene co-expression network structure. To examine this issue, we have created a new mouse resource, a heterogeneous stock (HS) formed from the same eight inbred strains that have been used to create the collaborative cross (CC). The eight inbred strains capture > 90% of the genetic diversity available within the species. For contrast with the HS-CC, a C57BL/6J (B6) × DBA/2J (D2) F2 intercross and the HS4, derived from crossing the B6, D2, BALB/cJ and LP/J strains, were used. Brain (striatum) gene expression data were obtained using the Illumina Mouse WG 6.1 array, and the data sets were interrogated using a weighted gene co-expression network analysis (WGCNA). Genes reliably detected as expressed were similar in all three data sets as was the variability of expression. As measured by the WGCNA, the modular structure of the transcriptome networks was also preserved both on the basis of module assignment and from the perspective of the topological overlap maps. Details of the HS-CC gene modules are provided; essentially identical results were obtained for the HS4 and F2 modules. Gene ontology annotation of the modules revealed a significant overrepresentation in some modules for neuronal processes, e.g., central nervous system development. Integration with known protein-protein interactions data indicated significant enrichment among co-expressed genes. We also noted significant overlap with markers of central nervous system cell types (neurons, oligodendrocytes and astrocytes). Using the Allen Brain Atlas, we found evidence of spatial co-localization within the striatum for several modules. Finally, for some modules it was possible to detect an enrichment of transcription binding sites. The binding site for Wt1, which is associated with neurodegeneration, was the most significantly overrepresented. Despite the marked differences in genetic diversity, the transcriptome

  15. Longitudinal study of striatal activation to reward and loss anticipation from mid-adolescence into late adolescence/early adulthood.

    Science.gov (United States)

    Lamm, C; Benson, B E; Guyer, A E; Perez-Edgar, K; Fox, N A; Pine, D S; Ernst, M

    2014-08-01

    Adolescent risk-taking behavior has been associated with age-related changes in striatal activation to incentives. Previous cross-sectional studies have shown both increased and decreased striatal activation to incentives for adolescents compared to adults. The monetary incentive delay (MID) task, designed to assess functional brain activation in anticipation of reward, has been used extensively to examine striatal activation in both adult and adolescent populations. The current study used this task with a longitudinal approach across mid-adolescence and late adolescence/early adulthood. Twenty-two participants (13 male) were studied using the MID task at two time-points, once in mid-adolescence (mean age=16.11; SD=1.44) and a second time in late adolescence/early adulthood (mean age=20.14; SD=.67). Results revealed greater striatal activation with increased age in high- compared to low-incentive contexts (incentive magnitude), for gain as well as for loss trials (incentive valence). Results extend cross-sectional findings and show reduced striatal engagement in adolescence compared to adulthood during preparation for action in an incentive context. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Predicting treatment response in schizophrenia: The role of striatal and frontal dopamine D2/D3 receptor binding potential

    DEFF Research Database (Denmark)

    Nørbak, Henrik; Wulff, Sanne; Nielsen, Mette Ødegaard

    included 25 patients. The ligand [123I]epidepride was used for quantification of extrastriatal dopamine D2/D3 receptors. Patients were randomised to twelve weeks of treatment with either risperidone or zuclopenthixol. Results: In the IBZMcohort the mean PANSS total score was 79 at baseline and 65 at follow...... group (Rho=-0,417 P=0,060). In the EPIcohort the mean PANSS total score was 70 at baseline and 48 at follow up. In the frontal cortex we found a positive correlation (Rho=0.56 P=0.003) between BP and change in positive symptom score for the whole group as well as in the subgroup treated with risperidone...

  17. Timing of caloric intake during weight loss differentially affects striatal dopamine transporter and thalamic serotonin transporter binding

    NARCIS (Netherlands)

    Versteeg, Ruth I.; Schrantee, Anouk; Adriaanse, Sofie M.; Unmehopa, Unga A.; Booij, Jan; Reneman, Liesbeth; Fliers, Eric; la Fleur, Susanne E.; Serlie, Mireille J.

    2017-01-01

    Recent studies have shown that meal timing throughout the day contributes to maintaining or regaining weight after hypocaloric diets. Although brain serotonin and dopamine are well known to be involved in regulating feeding, it is unknown whether meal timing during energy restriction affects these

  18. Automated striatal uptake analysis of 18F-FDOPA PET images applied to Parkinson's disease patients

    International Nuclear Information System (INIS)

    Chang Icheng; Lue Kunhan; Hsieh Hungjen; Liu Shuhsin; Kao, Chinhao K.

    2011-01-01

    6-[ 18 F]Fluoro-L-DOPA (FDOPA) is a radiopharmaceutical valuable for assessing the presynaptic dopaminergic function when used with positron emission tomography (PET). More specifically, the striatal-to-occipital ratio (SOR) of FDOPA uptake images has been extensively used as a quantitative parameter in these PET studies. Our aim was to develop an easy, automated method capable of performing objective analysis of SOR in FDOPA PET images of Parkinson's disease (PD) patients. Brain images from FDOPA PET studies of 21 patients with PD and 6 healthy subjects were included in our automated striatal analyses. Images of each individual were spatially normalized into an FDOPA template. Subsequently, the image slice with the highest level of basal ganglia activity was chosen among the series of normalized images. Also, the immediate preceding and following slices of the chosen image were then selected. Finally, the summation of these three images was used to quantify and calculate the SOR values. The results obtained by automated analysis were compared with manual analysis by a trained and experienced image processing technologist. The SOR values obtained from the automated analysis had a good agreement and high correlation with manual analysis. The differences in caudate, putamen, and striatum were -0.023, -0.029, and -0.025, respectively; correlation coefficients 0.961, 0.957, and 0.972, respectively. We have successfully developed a method for automated striatal uptake analysis of FDOPA PET images. There was no significant difference between the SOR values obtained from this method and using manual analysis. Yet it is an unbiased time-saving and cost-effective program and easy to implement on a personal computer. (author)

  19. Striatal fast-spiking interneurons: from firing patterns to postsynaptic impact

    Directory of Open Access Journals (Sweden)

    Andreas eKlaus

    2011-07-01

    Full Text Available In the striatal microcircuit, fast-spiking (FS interneurons have an important role in mediating inhibition onto neighboring medium spiny (MS projection neurons. In this study, we combined computational modeling with in vitro and in vivo electrophysiological measurements to investigate FS cells in terms of their discharge properties and their synaptic efficacies onto MS neurons. In vivo firing of striatal FS interneurons is characterized by a high firing variability. It is not known, however, if this variability results from the input that FS cells receive, or if it is promoted by the stuttering spike behavior of these neurons. Both our model and measurements in vitro show that FS neurons that exhibit random stuttering discharge in response to steady depolarization, do not show the typical stuttering behavior when they receive fluctuating input. Importantly, our model predicts that electrically coupled FS cells show substantial spike synchronization only when they are in the stuttering regime. Therefore, together with the lack of synchronized firing of striatal FS interneurons that has been reported in vivo, these results suggest that neighboring FS neurons are not in the stuttering regime simultaneously and that in vivo FS firing variability is more likely determined by the input fluctuations. Furthermore, the variability in FS firing is translated to variability in the postsynaptic amplitudes in MS neurons due to the strong synaptic depression of the FS-to-MS synapse. Our results support the idea that these synapses operate over a wide range from strongly depressed to almost fully recovered. The strong inhibitory effects that FS cells can impose on their postsynaptic targets, and the fact that the FS-to-MS synapse model showed substantial depression over extended periods of time might indicate the importance of cooperative effects of multiple presynaptic FS interneurons and the precise orchestration of their activity.

  20. Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype.

    Directory of Open Access Journals (Sweden)

    Ismael Huertas

    Full Text Available Parkinson's disease (PD patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA, a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36, intermediate (I, n = 22, and tremor-dominant (TD, n = 17 subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001 and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25% and I (45% patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.

  1. Striatal Volume Increases in Active Methamphetamine-Dependent Individuals and Correlation with Cognitive Performance

    Directory of Open Access Journals (Sweden)

    Rob R. Kydd

    2012-10-01

    Full Text Available The effect of methamphetamine (MA dependence on the structure of the human brain has not been extensively studied, especially in active users. Previous studies reported cortical deficits and striatal gains in grey matter (GM volume of abstinent MA abusers compared with control participants. This study aimed to investigate structural GM changes in the brains of 17 active MA-dependent participants compared with 20 control participants aged 18–46 years using voxel-based morphometry and region of interest volumetric analysis of structural magnetic resonance imaging data, and whether these changes might be associated with cognitive performance. Significant volume increases were observed in the right and left putamen and left nucleus accumbens of MA-dependent compared to control participants. The volumetric gain in the right putamen remained significant after Bonferroni correction, and was inversely correlated with the number of errors (standardised z-scores on the Go/No-go task. MA-dependent participants exhibited cortical GM deficits in the left superior frontal and precentral gyri in comparison to control participants, although these findings did not survive correction for multiple comparisons. In conclusion, consistent with findings from previous studies of abstinent users, active chronic MA-dependent participants showed significant striatal enlargement which was associated with improved performance on the Go/No-go, a cognitive task of response inhibition and impulsivity. Striatal enlargement may reflect the involvement of neurotrophic effects, inflammation or microgliosis. However, since it was associated with improved cognitive function, it is likely to reflect a compensatory response to MA-induced neurotoxicity in the striatum, in order to maintain cognitive function. Follow-up studies are recommended to ascertain whether this effect continues to be present following abstinence. Several factors may have contributed to the lack of more

  2. Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Naaijen, Jilly; Forde, Natalie J; Lythgoe, David J; Akkermans, Sophie E A; Openneer, Thaira J C; Dietrich, Andrea; Zwiers, Marcel P; Hoekstra, Pieter J; Buitelaar, Jan K

    2017-01-01

    Both Tourette's disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) have been related to abnormalities in glutamatergic neurochemistry in the fronto-striatal circuitry. TD and ADHD often co-occur and the neural underpinnings of this co-occurrence have been insufficiently investigated in prior studies. We used proton magnetic resonance spectroscopy (1H-MRS) in children between 8 and 12 years of age (TD n  = 15, ADHD n  = 39, TD + ADHD n  = 29, and healthy controls n  = 53) as an in vivo method of evaluating glutamate concentrations in the fronto-striatal circuit. Spectra were collected on a 3 Tesla Siemens scanner from two voxels in each participant: the anterior cingulate cortex (ACC) and the left dorsal striatum. LC-model was used to process spectra and generate glutamate concentrations in institutional units. A one-way analysis of variance was performed to determine significant effects of diagnostic group on glutamate concentrations. We did not find any group differences in glutamate concentrations in either the ACC (F (3132)  = 0.97, p  = 0.41) or striatum (F (3121)  = 0.59, p  = 0.62). Furthermore, variation in glutamate concentration in these regions was unrelated to age, sex, medication use, IQ, tic, or ADHD severity. Obsessive-compulsive (OC) symptoms were positively correlated with ACC glutamate concentration within the participants with TD (rho = 0.35, p uncorrected  = 0.02). We found no evidence for glutamatergic neuropathology in TD or ADHD within the fronto-striatal circuits. However, the correlation of OC-symptoms with ACC glutamate concentrations suggests that altered glutamatergic transmission is involved in OC-symptoms within TD, but this needs further investigation.

  3. Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

    Science.gov (United States)

    Webber, Emily S; Mankin, David E; Cromwell, Howard C

    2016-01-01

    The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats ( Rattus norvegicus ) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

  4. Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype.

    Science.gov (United States)

    Huertas, Ismael; Jesús, Silvia; Lojo, José Antonio; García-Gómez, Francisco Javier; Cáceres-Redondo, María Teresa; Oropesa-Ruiz, Juan Manuel; Carrillo, Fátima; Vargas-Gonzalez, Laura; Martín Rodríguez, Juan Francisco; Gómez-Garre, Pilar; García-Solís, David; Mir, Pablo

    2017-01-01

    Parkinson's disease (PD) patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA), a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT) availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36), intermediate (I, n = 22), and tremor-dominant (TD, n = 17) subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001) and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25%) and I (45%) patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.

  5. Convergence of dopamine and glutamate signalling onto striatal ERK activation in response to drugs of abuse.

    Directory of Open Access Journals (Sweden)

    Emma eCahill

    2014-01-01

    Full Text Available Despite their distinct targets, all addictive drugs commonly abused by humans evoke increases in dopamine (DA concentration within the striatum. The main DA G-Protein Coupled Receptors (GPCRs expressed by medium-sized spiny neurons (MSNs of the striatum are the D1R and D2R, which are positively and negatively coupled to cAMP/protein kinase A (PKA signalling, respectively. These two DA GPCRs are largely segregated into distinct neuronal populations, where they are co-expressed with glutamate receptors in dendritic spines. Direct and indirect interactions between DA GPCRs and glutamate receptors are the molecular basis by which DA modulates glutamate transmission and controls striatal plasticity and behaviour induced by drugs of abuse. A major downstream target of striatal D1R is the Extracellular signal-Regulated Kinase (ERK kinase pathway. ERK activation by drugs of abuse behaves as a key integrator of D1R and glutamate NMDAR signalling. Once activated, ERK can trigger chromatin remodelling and induce gene expression that permits long-term cellular alterations and drug-induced morphological and behavioural changes. Besides the classical cAMP/PKA pathway, downstream of D1R, recent evidence implicates a cAMP-independent crosstalk mechanism by which the D1R potentiates NMDAR-mediated calcium influx and ERK activation. The mounting evidence of reciprocal modulation of DA and glutamate receptors adds further intricacy to striatal synaptic signalling and is liable to prove relevant for addictive drug-induced signalling, plasticity and behaviour. Herein, we review the evidence that built our understanding of the consequences of this synergistic signalling for the actions of drugs of abuse.

  6. Near Misses in Slot Machine Gambling Developed Through Generalization of Total Wins.

    Science.gov (United States)

    Belisle, Jordan; Dixon, Mark R

    2016-06-01

    The purpose of the present study was to evaluate the development of the near miss effect in slot machine gambling as a product of stimulus generalization from total wins. The study was conducted across two experiments. Twelve college students participated in the first experiment, which demonstrated that greater post-reinforcement pauses followed losing outcomes that were formally similar to total wins, relative to losing outcomes that were formally dissimilar [F (5, 7) = 5.24, p = .025] along a generalization gradient (R (2) = .96). Additionally, 11 out of 12 participants showed greater response latencies following near-misses than following total wins. Thirteen college students participated in the second experiment, which demonstrated that symbols that more saliently indicated a loss resulted in lower response latencies than functionally equivalent but visually dissimilar losing symbols [F (3, 10) = 15.50, p = .01]. A generalization gradient was observed across winning symbols (R (2) = .98), and an inverse of the gradient observed across winning symbols was observed across symbols that were the least formally similar (R (2) = .69). The present study replicates and extends previous research on near misses in slot machine gambling, and provides discussion around the clinical utility of such findings on the prevention of problem gambling.

  7. Match statistics related to winning in the group stage of 2014 Brazil FIFA World Cup.

    Science.gov (United States)

    Liu, Hongyou; Gomez, Miguel-Ángel; Lago-Peñas, Carlos; Sampaio, Jaime

    2015-01-01

    Identifying match statistics that strongly contribute to winning in football matches is a very important step towards a more predictive and prescriptive performance analysis. The current study aimed to determine relationships between 24 match statistics and the match outcome (win, loss and draw) in all games and close games of the group stage of FIFA World Cup (2014, Brazil) by employing the generalised linear model. The cumulative logistic regression was run in the model taking the value of each match statistic as independent variable to predict the logarithm of the odds of winning. Relationships were assessed as effects of a two-standard-deviation increase in the value of each variable on the change in the probability of a team winning a match. Non-clinical magnitude-based inferences were employed and were evaluated by using the smallest worthwhile change. Results showed that for all the games, nine match statistics had clearly positive effects on the probability of winning (Shot, Shot on Target, Shot from Counter Attack, Shot from Inside Area, Ball Possession, Short Pass, Average Pass Streak, Aerial Advantage and Tackle), four had clearly negative effects (Shot Blocked, Cross, Dribble and Red Card), other 12 statistics had either trivial or unclear effects. While for the close games, the effects of Aerial Advantage and Yellow Card turned to trivial and clearly negative, respectively. Information from the tactical modelling can provide a more thorough and objective match understanding to coaches and performance analysts for evaluating post-match performances and for scouting upcoming oppositions.

  8. Winning fights induces hyperaggression via the action of the biogenic amine octopamine in crickets.

    Directory of Open Access Journals (Sweden)

    Jan Rillich

    Full Text Available Winning an agonistic interaction against a conspecific is known to heighten aggressiveness, but the underlying events and mechanism are poorly understood. We quantified the effect of experiencing successive wins on aggression in adult male crickets (Gryllus bimaculatus by staging knockout tournaments and investigated its dependence on biogenic amines by treatment with amine receptor antagonists. For an inter-fight interval of 5 min, fights between winners escalated to higher levels of aggression and lasted significantly longer than the preceding round. This winner effect is transient, and no longer evident for an inter-fight interval of 20 min, indicating that it does not result from selecting individuals that were hyper-aggressive from the outset. A winner effect was also evident in crickets that experienced wins without physical exertion, or that engaged in fights that were interrupted before a win was experienced. Finally, the winner effect was abolished by prior treatment with epinastine, a highly selective octopamine receptor blocker, but not by propranolol, a ß-adrenergic receptor antagonist, nor by yohimbine, an insect tyramine receptor blocker nor by fluphenazine an insect dopamine-receptor blocker. Taken together our study in the cricket indicates that the physical exertion of fighting, together with some rewarding aspect of the actual winning experience, leads to a transient increase in aggressive motivation via activation of the octopaminergic system, the invertebrate equivalent to the adrenergic system of vertebrates.

  9. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...

  10. Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation

    Science.gov (United States)

    Sameiro-Barbosa, Catia M.; Geiser, Eveline

    2016-01-01

    The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system. PMID:27559306

  11. Key modulatory role of presynaptic adenosine A2A receptors in cortical neurotransmission to the striatal direct pathway.

    Science.gov (United States)

    Quiroz, César; Luján, Rafael; Uchigashima, Motokazu; Simoes, Ana Patrícia; Lerner, Talia N; Borycz, Janusz; Kachroo, Anil; Canas, Paula M; Orru, Marco; Schwarzschild, Michael A; Rosin, Diane L; Kreitzer, Anatol C; Cunha, Rodrigo A; Watanabe, Masahiko; Ferré, Sergi

    2009-11-18

    Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D1 and D2 receptors, respectively. Adenosine A2A receptors are considered novel antiparkinsonian targets, based on their selective postsynaptic localization in the indirect pathway, where they modulate D2 receptor function. The present study provides evidence for the existence of an additional, functionally significant, segregation of A2A receptors at the presynaptic level. Using integrated anatomical, electrophysiological, and biochemical approaches, we demonstrate that presynaptic A2A receptors are preferentially localized in cortical glutamatergic terminals that contact striatal neurons of the direct pathway, where they exert a selective modulation of corticostriatal neurotransmission. Presynaptic striatal A2A receptors could provide a new target for the treatment of neuropsychiatric disorders.

  12. Key Modulatory Role of Presynaptic Adenosine A2A Receptors in Cortical Neurotransmission to the Striatal Direct Pathway

    Directory of Open Access Journals (Sweden)

    César Quiroz

    2009-01-01

    Full Text Available Basal ganglia processing results from a balanced activation of direct and indirect striatal efferent pathways, which are controlled by dopamine D1 and D2 receptors, respectively. Adenosine A2A receptors are considered novel antiparkinsonian targets, based on their selective postsynaptic localization in the indirect pathway, where they modulate D2 receptor function. The present study provides evidence for the existence of an additional, functionally significant, segregation of A2A receptors at the presynaptic level. Using integrated anatomical, electrophysiological, and biochemical approaches, we demonstrate that presynaptic A2A receptors are preferentially localized in cortical glutamatergic terminals that contact striatal neurons of the direct pathway, where they exert a selective modulation of corticostriatal neurotransmission. Presynaptic striatal A2A receptors could provide a new target for the treatment of neuropsychiatric disorders.

  13. Greenhouse Gas Emission Mitigation And Agriculture, Trade-off Or Win-win Situation: Bioeconomic Farm Modelling In The Sudanian Area of Burkina Faso

    Science.gov (United States)

    Some, T. E.; Barbier, B.

    2015-12-01

    Climate changes talks regularly underline that developing countries' agriculture could play a stronger role in GHGs mitigation strategies and benefit from the Kyoto Protocol program of subsidies. Scientists explain that agriculture can contribute to carbon mitigation by storing more carbon in the soil through greener cropping systems. In this context, a growing number of research projects have started to investigate how developing countries agriculture can contribute to these objectives. The clean development mechanism (CDM) proposed in the Kyoto protocol is one particular policy instrument that can incite farmers to mitigate the GHG balance towards more sequestration and less emission. Some economists such as Michael Porter think that environmental regulation lead to a win-win outcome, in which case subsidies are not necessary. If it is a trade-off between incomes and the environment, subsidies are required. CDM can be mobilized to support the mitigation strategy. Agriculture implies the use of inputs. Reducing the emission implies the reduction of those inputs which will in turn imply a yield decrease. The study aims to assess whether this measure will imply a trade-off between environmental and economic objectives or a win-win situation. I apply this study to the case of small farmers in Burkina Faso through environmental instruments such as the emissions limits and agroforestry using a bioeconomic model, in which the farmers maximize their utility subject to constraints. The study finds that the limitation of emissions in annual crops production involves a trade-off. by impacting negatively their net cash come. By integrating perennial crops in the farming system, the farmers' utility increases. Around 6,118 kg are sequestrated individually. By computing the value on this carbon balance, farmers' net cash incomes go better. Then practicing agroforestry is a win-win situation, as they reach a higher level of income, and reduce emissions. Policymakers must

  14. Neonatal astrocyte damage is sufficient to trigger progressive striatal degeneration in a rat model of glutaric acidemia-I.

    Directory of Open Access Journals (Sweden)

    Silvia Olivera-Bravo

    Full Text Available BACKGROUND: We have investigated whether an acute metabolic damage to astrocytes during the neonatal period may critically disrupt subsequent brain development, leading to neurodevelopmental disorders. Astrocytes are vulnerable to glutaric acid (GA, a dicarboxylic acid that accumulates in millimolar concentrations in Glutaric Acidemia I (GA-I, an inherited neurometabolic childhood disease characterized by degeneration of striatal neurons. While GA induces astrocyte mitochondrial dysfunction, oxidative stress and subsequent increased proliferation, it is presently unknown whether such astrocytic dysfunction is sufficient to trigger striatal neuronal loss. METHODOLOGY/PRINCIPAL FINDINGS: A single intracerebroventricular dose of GA was administered to rat pups at postnatal day 0 (P0 to induce an acute, transient rise of GA levels in the central nervous system (CNS. GA administration potently elicited proliferation of astrocytes expressing S100β followed by GFAP astrocytosis and nitrotyrosine staining lasting until P45. Remarkably, GA did not induce acute neuronal loss assessed by FluoroJade C and NeuN cell count. Instead, neuronal death appeared several days after GA treatment and progressively increased until P45, suggesting a delayed onset of striatal degeneration. The axonal bundles perforating the striatum were disorganized following GA administration. In cell cultures, GA did not affect survival of either striatal astrocytes or neurons, even at high concentrations. However, astrocytes activated by a short exposure to GA caused neuronal death through the production of soluble factors. Iron porphyrin antioxidants prevented GA-induced astrocyte proliferation and striatal degeneration in vivo, as well as astrocyte-mediated neuronal loss in vitro. CONCLUSIONS/SIGNIFICANCE: Taken together, these results indicate that a transient metabolic insult with GA induces long lasting phenotypic changes in astrocytes that cause them to promote striatal

  15. Ventral striatal activity correlates with memory confidence for old- and new-responses in a difficult recognition test.

    Directory of Open Access Journals (Sweden)

    Ulrike Schwarze

    Full Text Available Activity in the ventral striatum has frequently been associated with retrieval success, i.e., it is higher for hits than correct rejections. Based on the prominent role of the ventral striatum in the reward circuit, its activity has been interpreted to reflect the higher subjective value of hits compared to correct rejections in standard recognition tests. This hypothesis was supported by a recent study showing that ventral striatal activity is higher for correct rejections than hits when the value of rejections is increased by external incentives. These findings imply that the striatal response during recognition is context-sensitive and modulated by the adaptive significance of "oldness" or "newness" to the current goals. The present study is based on the idea that not only external incentives, but also other deviations from standard recognition tests which affect the subjective value of specific response types should modulate striatal activity. Therefore, we explored ventral striatal activity in an unusually difficult recognition test that was characterized by low levels of confidence and accuracy. Based on the human uncertainty aversion, in such a recognition context, the subjective value of all high confident decisions is expected to be higher than usual, i.e., also rejecting items with high certainty is deemed rewarding. In an accompanying behavioural experiment, participants rated the pleasantness of each recognition response. As hypothesized, ventral striatal activity correlated in the current unusually difficult recognition test not only with retrieval success, but also with confidence. Moreover, participants indicated that they were more satisfied by higher confidence in addition to perceived oldness of an item. Taken together, the results are in line with the hypothesis that ventral striatal activity during recognition codes the subjective value of different response types that is modulated by the context of the recognition test.

  16. The WIN-Speller: A new Intuitive Auditory Brain-Computer Interface Spelling Application

    Directory of Open Access Journals (Sweden)

    Sonja C Kleih

    2015-10-01

    Full Text Available The objective of this study was to test the usability of a new auditory Brain-Computer Interface (BCI application for communication. We introduce a word based, intuitive auditory spelling paradigm the WIN-speller. In the WIN-speller letters are grouped by words, such as the word KLANG representing the letters A, G, K, L and N. Thereby, the decoding step between perceiving a code and translating it to the stimuli it represents becomes superfluous. We tested 11 healthy volunteers and 4 end-users with motor impairment in the copy spelling mode. Spelling was successful with an average accuracy of 84% in the healthy sample. Three of the end-users communicated with average accuracies of 80% or higher while one user was not able to communicate reliably. Even though further evaluation is required, the WIN-speller represents a potential alternative for BCI based communication in end-users.

  17. Compensating for Missing Data from Longitudinal Studies Using WinBUGS

    Directory of Open Access Journals (Sweden)

    Gretchen Carrigan

    2007-06-01

    Full Text Available Missing data is a common problem in survey based research. There are many packages that compensate for missing data but few can easily compensate for missing longitudinal data. WinBUGS compensates for missing data using multiple imputation, and is able to incorporate longitudinal structure using random effects. We demonstrate the superiority of longitudinal imputation over cross-sectional imputation using WinBUGS. We use example data from the Australian Longitudinal Study on Women’s Health. We give a SAS macro that uses WinBUGS to analyze longitudinal models with missing covariate date, and demonstrate its use in a longitudinal study of terminal cancer patients and their carers.

  18. The political economy of local government in Croatia: winning coalitions, corruption, and taxes

    Directory of Open Access Journals (Sweden)

    Vuk Vukovic

    2017-12-01

    Full Text Available This paper represents the first comprehensive effort to provide a theoretical and empirical explanation of systemic corruption in Croatian local government. It follows the logic of the selectorate theory, according to which staying in power for long periods of time depends on creating a small group of loyal but powerful supporters (the winning coalition. Mayors that exist within such environments not only maximize their chances of staying in power; they also engage in greater corruption and set higher taxes. Its citizens are stuck in a negative spiral of corruption, high taxes, and a politician that regardless of this keeps winning elections. The paper makes two main contributions to the current literature. First it provides a theoretical extension of the selectorate theory to Croatian local government by explicitly modeling the link between corruption and winning coalitions, and second, it empirically verifies the theoretical findings using a novel matching approach called entropy balancing.

  19. Gambling warning messages: The impact of winning and losing on message reception across a gambling session.

    Science.gov (United States)

    Ginley, Meredith K; Whelan, James P; Keating, Holly A; Meyers, Andrew W

    2016-12-01

    Gambling warning messages have been shown to lead to prevention and modification of risk-taking behaviors. Laboratory studies have shown messages can increase a player's knowledge about gambling specific risks, modify their gambling-related cognitive distortions, and even change play. In the present laboratory study, participants were randomly assigned to a winning or losing slot machine gambling experience where they either viewed periodic warning messages or not. It was hypothesized that those in the message conditions would place smaller bets, spend more time considering bets, and spend less time gambling than those in the control conditions. We also hypothesized participants would play differently across the contexts of winning or losing. The results showed those who received warning messages while winning made the fewest number of spins and did not speed up their bet rate over the course of play as much as those in other conditions. Players who received warning messages while losing decreased the size of their bets over the course of play compared to those who received messages while winning. Despite receiving warning messages, losing players did not decrease their number of spins or rate of betting. Winning or losing during slot machine play appears to have significant consequences on the impact of a warning message. Whereas a message to change gambling behavior may encourage a winning gambler to stop play, the same message for a losing player may lead to a small minimization in harm by helping them to decrease bet size, though not their rate of betting. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. What Can WiN Learn From Other Male Dominated Industries

    International Nuclear Information System (INIS)

    Thomas, C.

    2015-01-01

    Thomas Thor Associates is an Executive Recruitment company solely dedicated to the Nuclear industry. We have been involved with WiN UK in 2014–2015 to help them develop their own organization, this research was part of our partnership. The main purpose of this paper is to provide a clear picture of the techniques that are used by organizations similar to WiN, and business in other industries that are similar to Nuclear, to attract more women to pursue a career in a particular industry, and to support retention and career progression of women in these industries. This paper has taken a look at all industries that require technical and engineering staff, after which the Mining, Oil and Gas, Petro-chemicals, Rail, Renewable Energy, Technology and Construction industries were found to show most similarities with Nuclear, in terms of the technical staff required and their structure on gender diversity. From here, case studies of industry organizations and professional business have been prepared in order to inform WiN of best practice in these industries and provide a benchmark for future WiN operations. Finally, the report results into giving recommendations on projects WiN could add to their current approach to achieve their objectives. The recommendations are based on the results from the case studies, focusing on attracting, recruiting, retaining and developing female professionals. In summary, the recommendations are to: highlight potential career paths for women in Nuclear, educate women on Nuclear, support the development of women and to help companies to increase their bottom line by getting WiN certified. (author)

  1. Modulation of acetylcholine release from rat striatal slices by the GABA/benzodiazepine receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Supavilai, P.; Karobath, M.

    1985-02-04

    GABA, THIP and muscimol enhance spontaneous and inhibit electrically induced release of tritium labelled compounds from rat striatal slices which have been pre-labelled with /sup 3/H-choline. Baclofen is inactive in this model. Muscimol can inhibit electrically induced release of tritiated material by approximately 75% with half maximal effects at 2 ..mu..M. The response to muscimol can be blocked by the GABA antagonists bicuculline methobromide, picrotoxin, anisatin, R 5135 and CPTBO (cyclopentylbicyclophosphate). Drugs which act on the benzodiazepine receptor (BR) require the presence of muscimol to be effective and they modulate the effects of muscimol in a bidirectional manner. Thus BR agonists enhance and inverse BR agonists attenuate the inhibitory effects of muscimol on electrically induced release. Ro15-1788, a BR antagonist, does not modulate the inhibitory effects of muscimol but antagonizes the actions of clonazepam, a BR agonist, and of DMCM, an inverse BR agonist. These results demonstrate that a GABA/benzodiazepine receptor complex can modulate acetylcholine release from rat striatal slices in vitro. 24 references, 3 figures, 5 table.

  2. Effects of caffeine on striatal neurotransmission: focus on cannabinoid CB1 receptors.

    Science.gov (United States)

    Rossi, Silvia; De Chiara, Valentina; Musella, Alessandra; Mataluni, Giorgia; Sacchetti, Lucia; Siracusano, Alberto; Bernardi, Giorgio; Usiello, Alessandro; Centonze, Diego

    2010-04-01

    Caffeine is the most commonly self-administered psychoactive substance worldwide. At usual doses, the effects of caffeine on vigilance, attention, mood and arousal largely depend on the modulation of central adenosine receptors. The present review article describes the action of caffeine within the striatum, to provide a possible molecular mechanism at the basis of the psychomotor and reinforcing properties of this pharmacological agent. The striatum is in fact a subcortical area involved in sensorimotor, cognitive, and emotional processes, and recent experimental findings showed that chronic caffeine consumption enhances the sensitivity of striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptors. The endocannabinoid system is involved in the psychoactive effects of many compounds, and adenosine A2A receptors (the main receptor target of caffeine) elicit a permissive effect towards CB1 receptors, thus suggesting that A2A-CB1 receptor interaction plays a major role in the generation and maintenance of caffeine reinforcing behavior. Aim of this review is to describe the effects of caffeine on striatal neurotransmission with special reference to the modulation of the endocannabinoid system.

  3. Levodopa administration modulates striatal processing of punishment-associated items in healthy participants.

    Science.gov (United States)

    Wittmann, Bianca C; D'Esposito, Mark

    2015-01-01

    Appetitive and aversive processes share a number of features such as their relevance for action and learning. On a neural level, reward and its predictors are associated with increased firing of dopaminergic neurons, whereas punishment processing has been linked to the serotonergic system and to decreases in dopamine transmission. Recent data indicate, however, that the dopaminergic system also responds to aversive stimuli and associated actions. In this pharmacological functional magnetic resonance imaging study, we investigated the contribution of the dopaminergic system to reward and punishment processing in humans. Two groups of participants received either placebo or the dopamine precursor levodopa and were scanned during alternating reward and punishment anticipation blocks. Levodopa administration increased striatal activations for cues presented in punishment blocks. In an interaction with individual personality scores, levodopa also enhanced striatal activation for punishment-predictive compared with neutral cues in participants scoring higher on the novelty-seeking dimension. These data support recent indications that dopamine contributes to punishment processing and suggest that the novelty-seeking trait is a measure of susceptibility to drug effects on motivation. These findings are also consistent with the possibility of an inverted U-shaped response function of dopamine in the striatum, suggesting an optimal level of dopamine release for motivational processing.

  4. KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

    Directory of Open Access Journals (Sweden)

    M. Belén Pérez-Ramírez

    2015-01-01

    Full Text Available Striatal projection neurons (SPNs process motor and cognitive information. Their activity is affected by Parkinson’s disease, in which dopamine concentration is decreased and acetylcholine concentration is increased. Acetylcholine activates muscarinic receptors in SPNs. Its main source is the cholinergic interneuron that responds with a briefer latency than SPNs during a cortical command. Therefore, an important question is whether muscarinic G-protein coupled receptors and their signaling cascades are fast enough to intervene during synaptic responses to regulate synaptic integration and firing. One of the most known voltage dependent channels regulated by muscarinic receptors is the KV7/KCNQ channel. It is not known whether these channels regulate the integration of suprathreshold corticostriatal responses. Here, we study the impact of cholinergic muscarinic modulation on the synaptic response of SPNs by regulating KV7 channels. We found that KV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines compartment. In contrast, it is negligible in the somatic compartment. This modulation occurs on sub- and suprathreshold responses and lasts during the whole duration of the responses, hundreds of milliseconds, greatly altering SPNs firing properties. This modulation affected the behavior of the striatal microcircuit.

  5. Cortico-striatal oxidative status, dopamine turnover and relation with stereotypy in the deer mouse.

    Science.gov (United States)

    Güldenpfennig, Marianne; Wolmarans, De Wet; du Preez, Jan L; Stein, Dan J; Harvey, Brian H

    2011-06-01

    The deer mouse presents with spontaneous stereotypic movements that resemble the repetitive behaviours of obsessive-compulsive disorder (OCD), and demonstrates a selective response to serotonin reuptake inhibitors. OCD has been linked to altered redox status and since increased dopamine signalling can promote stereotypies as well as oxidative stress, we investigated whether the severity of deer mouse stereotypy may be associated with altered dopamine turnover and cortico-striatal redox status. Deer mice were separated into high (HSB), low (LSB) and non-stereotypy (NS) groups. Frontal cortical and striatal dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as superoxide dismutase (SOD) activity, reduced (GSH) and oxidised (GSSG) glutathione and glutathione redox index, were analysed as markers for regional dopamine turnover and oxidative stress, respectively. Dopamine and its metabolites and SOD activity did not differ across the stereotypy groups. Significantly reduced GSH and GSSG and increased glutathione redox index were only observed in the frontal cortex of HSB animals. Frontal cortical GSH and GSSG were inversely correlated while glutathione redox index was positively correlated with stereotypy. Deer mouse stereotypy is thus characterised by a deficient glutathione system in the frontal cortex but not striatum, and provides a therapeutic rationale for using glutathione-active antioxidants in OCD. The evidence for a primary frontal lesion has importance for future OCD research. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Phasic dopamine release drives rapid activation of striatal D2-receptors

    Science.gov (United States)

    Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P

    2014-01-01

    Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

  7. Somatostatin regulates dopamine release in rat striatal slices and cat caudate nuclei

    International Nuclear Information System (INIS)

    Chesselet, M.F.; Reisine, T.D.

    1983-01-01

    The effects of somatostatin on the release of tritiated dopamine (DA) formed continuously from tritiated tyrosine were studied in vitro in superfused striatal slices and in vivo in both caudate nuclei and both substantiae nigrae of halothane-anesthetized cats using a push-pull cannula technique. Somatostatin (3 X 10(-10) to 3 X 10(-7) M) increased the spontaneous tritiated dopamine release from rat striatal slices. This effect was dose dependent and was completely prevented by tetrodotoxin (5 X 10(-7) M). When applied for 30 min in one cat caudate nucleus, somatostatin (10(-7) M) immediately increased the local release of tritiated DA, while a gradual inhibition of the tritiated amine's efflux was observed in the contralateral caudate nucleus. No changes in tritiated dopamine were seen in either substantia nigra during or after the peptide's application in the caudate nucleus. These results suggest that somatostatin in the striatum may play a role in the local and the distal control of dopamine release from the terminals of dopaminergic nigrostriatal neurons

  8. FACS identifies unique cocaine-induced gene regulation in selectively activated adult striatal neurons.

    Science.gov (United States)

    Guez-Barber, Danielle; Fanous, Sanya; Golden, Sam A; Schrama, Regina; Koya, Eisuke; Stern, Anna L; Bossert, Jennifer M; Harvey, Brandon K; Picciotto, Marina R; Hope, Bruce T

    2011-03-16

    Numerous studies with the neural activity marker Fos indicate that cocaine activates only a small proportion of sparsely distributed striatal neurons. Until now, efficient methods were not available to assess neuroadaptations induced specifically within these activated neurons. We used fluorescence-activated cell sorting (FACS) to purify striatal neurons activated during cocaine-induced locomotion in naive and cocaine-sensitized cfos-lacZ transgenic rats. Activated neurons were labeled with an antibody against β-galactosidase, the protein product of the lacZ gene. Cocaine induced a unique gene expression profile selectively in the small proportion of activated neurons that was not observed in the nonactivated majority of neurons. These genes included altered levels of the immediate early genes arc, fosB, and nr4a3, as well as genes involved in p38 MAPK signaling and cell-type specificity. We propose that this FACS method can be used to study molecular neuroadaptations in specific neurons encoding the behavioral effects of abused drugs and other learned behaviors.

  9. DRD4 and striatal modulation of the link between childhood behavioral inhibition and adolescent anxiety

    Science.gov (United States)

    Hardee, Jillian E.; Guyer, Amanda E.; Benson, Brenda E.; Nelson, Eric E.; Gorodetsky, Elena; Goldman, David; Fox, Nathan A.; Pine, Daniel S.; Ernst, Monique

    2014-01-01

    Behavioral inhibition (BI), a temperament characterized by vigilance to novelty, sensitivity to approach–withdrawal cues and social reticence in childhood, is associated with risk for anxiety in adolescence. Independent studies link reward hyper-responsivity to BI, adolescent anxiety and dopamine gene variants. This exploratory study extends these observations by examining the impact of DRD4 genotype and reward hyper-responsivity on the BI–anxiety link. Adolescents (N = 78) completed a monetary incentive delay task in the fMRI environment. Participants were characterized based on a continuous score of BI and the 7-repeat allele (7R+) of the DRD4 functional polymorphism. Parent-report and self-report measures of anxiety were also collected. Across the entire sample, striatal activation increased systematically with increases in the magnitude of anticipated monetary gains and losses. DRD4 status moderated the relation between BI and activation in the caudate nucleus. Childhood BI was associated with parent report of adolescent anxiety among 7R+ participants with elevated levels of striatal response to incentive cues. DRD4 genotype influenced the relations among neural response to incentives, early childhood BI and anxiety. The findings help refine our understanding of the role reward-related brain systems play in the emergence of anxiety in temperamentally at-risk individuals, building a foundation for future larger scale studies. PMID:23314010

  10. Compromised fronto-striatal functioning in HIV: an fMRI investigation of semantic event sequencing.

    Science.gov (United States)

    Melrose, Rebecca J; Tinaz, Sule; Castelo, J Mimi Boer; Courtney, Maureen G; Stern, Chantal E

    2008-04-09

    The human immunodeficiency virus (HIV) damages fronto-striatal regions, and is associated with deficits in executive functioning. We recently developed a semantic event sequencing task based on the Picture Arrangement subtest of the Wechsler Adult Intelligence Scale-III for use with functional magnetic resonance imaging (fMRI) and found recruitment of dorsolateral prefrontal cortex and basal ganglia in healthy participants. To assess the impact of HIV on the functioning of the basal ganglia and prefrontal cortex, we administered this task to 11 HIV+ and 11 Control participants matched for age and education. Neuropsychological evaluation demonstrated that the HIV+ group had mild impairment in memory retrieval and motor functioning, but was not demented. Morphometric measurements suggested no atrophy in basal ganglia regions. The results of the fMRI analysis revealed hypoactivation of the left caudate, left dorsolateral prefrontal cortex, and bilateral ventral prefrontal cortex in the HIV+ group. Functional connectivity analysis demonstrated less functional connectivity between the caudate and prefrontal cortex and basal ganglia regions in the HIV+ group. In contrast, the HIV+ group demonstrated increased activation of right postcentral/supramarginal gyrus, and greater connectivity between the caudate and this same anterior parietal region. The results of this study extend previous investigations by demonstrating compromised function of the caudate and connected prefrontal regions in HIV during cognition. This disruption of fronto-striatal circuitry likely precedes the development of cognitive impairment in HIV.

  11. Optogenetic approaches to evaluate striatal function in animal models of Parkinson disease.

    Science.gov (United States)

    Parker, Krystal L; Kim, Youngcho; Alberico, Stephanie L; Emmons, Eric B; Narayanan, Nandakumar S

    2016-03-01

    Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels. The introduction of optogenetic approaches has facilitated the dissection of neural circuits. Optogenetics allows for the precise stimulation and inhibition of specific sets of neurons and their projections with fine temporal specificity. These techniques are ideally suited to investigating neural circuitry underlying motor and cognitive dysfunction in animal models of human disease. Here, we focus on how optogenetics has been used over the last decade to probe striatal circuits that are involved in Parkinson disease, a neurodegenerative condition involving motor and cognitive abnormalities resulting from degeneration of midbrain dopaminergic neurons. The precise mechanisms underlying the striatal contribution to both cognitive and motor dysfunction in Parkinson disease are unknown. Although optogenetic approaches are somewhat removed from clinical use, insight from these studies can help identify novel therapeutic targets and may inspire new treatments for Parkinson disease. Elucidating how neuronal and behavioral functions are influenced and potentially rescued by optogenetic manipulation in animal models could prove to be translatable to humans. These insights can be used to guide future brain-stimulation approaches for motor and cognitive abnormalities in Parkinson disease and other neuropsychiatric diseases.

  12. Episodic Memory Encoding Interferes with Reward Learning and Decreases Striatal Prediction Errors

    Science.gov (United States)

    Braun, Erin Kendall; Daw, Nathaniel D.

    2014-01-01

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. PMID:25378157

  13. Low striatal glutamate levels underlie cognitive decline in the elderly: evidence from in vivo molecular spectroscopy.

    Science.gov (United States)

    Zahr, Natalie M; Mayer, Dirk; Pfefferbaum, Adolf; Sullivan, Edith V

    2008-10-01

    Glutamate (Glu), the principal excitatory neurotransmitter of prefrontal cortical efferents, potentially mediates higher order cognitive processes, and its altered availability may underlie mechanisms of age-related decline in frontally based functions. Although animal studies support a role for Glu in age-related cognitive deterioration, human studies, which require magnetic resonance spectroscopy for in vivo measurement of this neurotransmitter, have been impeded because of the similarity of Glu's spectroscopic signature to those of neighboring spectral brain metabolites. Here, we used a spectroscopic protocol, optimized for Glu detection, to examine the effect of age in 3 brain regions targeted by cortical efferents--the striatum, cerebellum, and pons--and to test whether performance on frontally based cognitive tests would be predicted by regional Glu levels. Healthy elderly men and women had lower Glu in the striatum but not pons or cerebellum than young adults. In the combined age groups, levels of striatal Glu (but no other proton metabolite also measured) correlated selectively with performance on cognitive tests showing age-related decline. The selective relations between performance and striatal Glu provide initial and novel, human in vivo support for age-related modification of Glu levels as contributing to cognitive decline in normal aging.

  14. Clinical report on and CT findings in two siblings with bilateral striatal necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Maya, Kiyomi; Imai, Terukuni; Hashimoto, Shuji; Yamasaki, Masahiro (Kitano Hospital, Osaka (Japan)); Kajiura, Ichiro

    1983-12-01

    Two siblings, a 13-year-old girl and a 9-year-old boy, presented a similar progressive extrapyramidal disorder. The onsets were at the age of 4 years and at that of 2 1/2 years respectively, and a certain febrile illness had preceded it for two or three months in both cases. The major clinical features were progressive gait disturbance, dysarthria, and dystonia; they were associated with secondary skeletal deformities in the sister and with abnormal ocular movements in the brother. The CT findings, essentially similar in both cases, were characterized by symmetrical hypodensity lesions and an atrophy of the corpora striata, namely, the putamen and the caudate nucleus. Based on the clinical features and the CT findings, and on a comparison with the previous clinico-pathological reports in the literature, the present cases were diagnosed as bilateral striatal necrosis. The disorder termed ''bilateral striatal necrosis'' has not been widely known; this report stresses the great usefulness of CT examination in the clinical diagnosis of this rare disorder.

  15. Emotion-induced loss aversion and striatal-amygdala coupling in low-anxious individuals.

    Science.gov (United States)

    Charpentier, Caroline J; De Martino, Benedetto; Sim, Alena L; Sharot, Tali; Roiser, Jonathan P

    2016-04-01

    Adapting behavior to changes in the environment is a crucial ability for survival but such adaptation varies widely across individuals. Here, we asked how humans alter their economic decision-making in response to emotional cues, and whether this is related to trait anxiety. Developing an emotional decision-making task for functional magnetic resonance imaging, in which gambling decisions were preceded by emotional and non-emotional primes, we assessed emotional influences on loss aversion, the tendency to overweigh potential monetary losses relative to gains. Our behavioral results revealed that only low-anxious individuals exhibited increased loss aversion under emotional conditions. This emotional modulation of decision-making was accompanied by a corresponding emotion-elicited increase in amygdala-striatal functional connectivity, which correlated with the behavioral effect across participants. Consistent with prior reports of 'neural loss aversion', both amygdala and ventral striatum tracked losses more strongly than gains, and amygdala loss aversion signals were exaggerated by emotion, suggesting a potential role for this structure in integrating value and emotion cues. Increased loss aversion and striatal-amygdala coupling induced by emotional cues may reflect the engagement of adaptive harm-avoidance mechanisms in low-anxious individuals, possibly promoting resilience to psychopathology. © The Author (2015). Published by Oxford University Press.

  16. Perineuronal nets play a role in regulating striatal function in the mouse.

    Directory of Open Access Journals (Sweden)

    Hyunchul Lee

    Full Text Available The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs, aggregations of chondroitin-sulfate proteoglycans (CSPGs, form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41% of these structures surrounds parvalbumin positive (PV+ interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.

  17. Perineuronal nets play a role in regulating striatal function in the mouse.

    Science.gov (United States)

    Lee, Hyunchul; Leamey, Catherine A; Sawatari, Atomu

    2012-01-01

    The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs), aggregations of chondroitin-sulfate proteoglycans (CSPGs), form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41%) of these structures surrounds parvalbumin positive (PV+) interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.

  18. Episodic memory encoding interferes with reward learning and decreases striatal prediction errors.

    Science.gov (United States)

    Wimmer, G Elliott; Braun, Erin Kendall; Daw, Nathaniel D; Shohamy, Daphna

    2014-11-05

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. Copyright © 2014 the authors 0270-6474/14/3414901-12$15.00/0.

  19. Representations in Award-Winning LGBTQ Young Adult Literature from 2000-2013.

    Science.gov (United States)

    Jiménez, Laura M

    2015-01-01

    Lesbian, gay, bisexual, transgendered, and queer (LGBTQ) young adult (YA) literature is increasing in popularity, with novels like Bil Wright's Putting Makeup on the Fat Boy winning the two LGBTQ YA honors--the Lambda Literary and Stonewall Book Awards--as well awards commending their cultural diversity. Despite the upsurge of celebrated LGBTQ YA literature, a study of the protagonists in Lambda- and Stonewall-winning YA novels from 2000-2013 reveals three findings: the dominance of White, gay, male characters contradicts the trend toward strong female protagonists in mainstream YA; stories about lesbians are primarily tragic; and there are no bisexual protagonists.

  20. Digital image processing in the nuclear field with ImaWin 5.0

    International Nuclear Information System (INIS)

    Marajofsky, A.; Trafelati, A.A.; Lavagnino, C.E.

    2000-01-01

    ImaWin is a software project designed to cover a broad set of applications of Digital Image Processing in the Nuclear Field. Since 1994 the system has evolved in a complete tool that helped to face problems like densitometry calculus, quality control in pellets, deposit administration and surveillance. Neural network kernel and ImaScript scripting language are included within the package. The open and incremental development of ImaWin software has been allowing easy expansion upon a common re-engineering framework. (author)

  1. A2A adenosine receptor ligand binding and signalling is allosterically modulated by adenosine deaminase.

    Science.gov (United States)

    Gracia, Eduard; Pérez-Capote, Kamil; Moreno, Estefanía; Barkešová, Jana; Mallol, Josefa; Lluís, Carme; Franco, Rafael; Cortés, Antoni; Casadó, Vicent; Canela, Enric I

    2011-05-01

    A2ARs (adenosine A2A receptors) are highly enriched in the striatum, which is the main motor control CNS (central nervous system) area. BRET (bioluminescence resonance energy transfer) assays showed that A2AR homomers may act as cell-surface ADA (adenosine deaminase; EC 3.5.4.4)-binding proteins. ADA binding affected the quaternary structure of A2ARs present on the cell surface. ADA binding to adenosine A2ARs increased both agonist and antagonist affinity on ligand binding to striatal membranes where these proteins are co-expressed. ADA also increased receptor-mediated ERK1/2 (extracellular-signal-regulated kinase 1/2) phosphorylation. Collectively, the results of the present study show that ADA, apart from regulating the concentration of extracellular adenosine, may behave as an allosteric modulator that markedly enhances ligand affinity and receptor function. This powerful regulation may have implications for the physiology and pharmacology of neuronal A2ARs.

  2. WIN 55,212-2 Inhibits the Epithelial Mesenchymal Transition of Gastric Cancer Cells via COX-2 Signals

    Directory of Open Access Journals (Sweden)

    Xiangshu Xian

    2016-11-01

    Full Text Available Background: Cannabinoids (the active components of Cannabis sativa and their derivatives have received considerable interest due to reports that they can affect the tumor growth, migration, and metastasis. Previous studies showed that the cannabinoid agonist WIN 55,212-2 (WIN was associated with gastric cancer (GC metastasis, but the mechanisms were unknown. Methods: The effects of WIN on GC cell migration and invasion were analyzed by the wound-healing assay and Transwell assay. Quantitative real-time PCR and Western blot were used to evaluate changes in expression of COX-2 and EMT associated markers in SGC7901 and AGS cells. Results: WIN inhibited cell migration, invasion, and epithelial to mesenchymal transition (EMT in GC. WIN treatment resulted in the downregulation of cyclooxygenase-2 (COX-2 expression and decreased the phosphorylation of AKT, and inhibited EMT in SGC7901 cells. Decreased expression of COX-2 and vimentin, and increased expression of E-cadherin, which was induced by WIN, were normalized by overexpression of AKT, suggesting that AKT mediated, at least partially, the WIN suppressed EMT of GC cells. Conclusion: WIN can inhibit the EMT of GC cells through the downregulation of COX-2.

  3. Regional GABA concentration and [3H]-diazepam binding in rat brain following repeated electroconvulsive shock

    International Nuclear Information System (INIS)

    Bowdler, J.M.; Green, A.R.; Minchin, M.C.W.; Nutt, D.J.

    1983-01-01

    It has been confirmed that 24 hours following a series of electroconvulsive shocks (ECS) given once daily for 10 days (ECS x 10) to rats there is an increase in GABA concentration in the corpus striatum. A similar change was seen after the ECS had been given to rats anaesthetised with halothane, or when 5 ECS were given spread out over 10 days, the rats being anaesthetised during the ECS. A daily convulsion for 10 days elicited by flurothyl exposure resulted in an increased striatal GABA concentration, but also increased the GABA concentration in the hypothalamus, hippocampus and cortex. The increase in striatal GABA concentration was present 24 hours after ECS daily for 5 days or 3 days after ECS daily for 10 days. No change in [ 3 H]-diazepam binding was seen in hippocampus, cortex or corpus striatum 24 hours after the last of 10 once daily ECS. The increase in striatal GABA concentration was therefore seen at all times when enhanced monoaminemediated behaviours have been demonstrated following seizures. (Author)

  4. Presynaptic Dopamine Synthesis Capacity in Schizophrenia and Striatal Blood Flow Change During Antipsychotic Treatment and Medication-Free Conditions.

    Science.gov (United States)

    Eisenberg, Daniel Paul; Yankowitz, Lisa; Ianni, Angela M; Rubinstein, Dani Y; Kohn, Philip D; Hegarty, Catherine E; Gregory, Michael D; Apud, José A; Berman, Karen F

    2017-10-01

    Standard-of-care biological treatment of schizophrenia remains dependent upon antipsychotic medications, which demonstrate D 2 receptor affinity and elicit variable, partial clinical responses via neural mechanisms that are not entirely understood. In the striatum, where D 2 receptors are abundant, antipsychotic medications may affect neural function in studies of animals, healthy volunteers, and patients, yet the relevance of this to pharmacotherapeutic actions remains unresolved. In this same brain region, some individuals with schizophrenia may demonstrate phenotypes consistent with exaggerated dopaminergic signaling, including alterations in dopamine synthesis capacity; however, the hypothesis that dopamine system characteristics underlie variance in medication-induced regional blood flow changes has not been directly tested. We therefore studied a cohort of 30 individuals with schizophrenia using longitudinal, multi-session [ 15 O]-water and [ 18 F]-FDOPA positron emission tomography to determine striatal blood flow during active atypical antipsychotic medication treatment and after at least 3 weeks of placebo treatment, along with presynaptic dopamine synthesis capacity (ie, DOPA decarboxylase activity). Regional striatal blood flow was significantly higher during active treatment than during the placebo condition. Furthermore, medication-related increases in ventral striatal blood flow were associated with more robust amelioration of excited factor symptoms during active medication and with higher dopamine synthesis capacity. These data indicate that atypical medications enact measureable physiological alterations in limbic striatal circuitry that vary as a function of dopaminergic tone and may have relevance to aspects of therapeutic responses.

  5. Differences in spontaneously avoiding or approaching mice reflect differences in CB1-mediated signaling of dorsal striatal transmission.

    Directory of Open Access Journals (Sweden)

    Daniela Laricchiuta

    Full Text Available Approach or avoidance behaviors are accompanied by perceptual vigilance for, affective reactivity to and behavioral predisposition towards rewarding or punitive stimuli, respectively. We detected three subpopulations of C57BL/6J mice that responded with avoiding, balancing or approaching behaviors not induced by any experimental manipulation but spontaneously displayed in an approach/avoidance conflict task. Although the detailed neuronal mechanisms underlying the balancing between approach and avoidance are not fully clarified, there is growing evidence that endocannabinoid system (ECS plays a critical role in the control of these balancing actions. The sensitivity of dorsal striatal synapses to the activation of cannabinoid CB1 receptors was investigated in the subpopulations of spontaneously avoiding, balancing or approaching mice. Avoiding animals displayed decreased control of CB1 receptors on GABAergic striatal transmission and in parallel increase of behavioral inhibition. Conversely, approaching animals exhibited increased control of CB1 receptors and in parallel increase of explorative behavior. Balancing animals reacted with balanced responses between approach and avoidance patterns. Treating avoiding animals with URB597 (fatty acid amide hydrolase inhibitor or approaching animals with AM251 (CB1 receptor inverse agonist reverted their respective behavioral and electrophysiological patterns. Therefore, enhanced or reduced CB1-mediated control on dorsal striatal transmission represents the synaptic hallmark of the approach or avoidance behavior, respectively. Thus, the opposite spontaneous responses to conflicting stimuli are modulated by a different involvement of endocannabinoid signaling of dorsal striatal neurons in the range of temperamental traits related to individual differences.

  6. Aberrant neural signatures of decision-making: Pathological gamblers display cortico-striatal hypersensitivity to extreme gambles

    DEFF Research Database (Denmark)

    Gelskov, Sofie V.; Madsen, Kristoffer Hougaard; Ramsøy, Thomas Z.

    2016-01-01

    bets in an executive cortico-striatal network including the dorsolateral prefrontal cortex and caudate nucleus. This network is concerned with the evaluation of action-outcome contingencies, monitoring recent actions and anticipating their consequences. The dysregulation of this specific network...

  7. Adenosine A₂A receptors in striatal glutamatergic terminals and GABAergic neurons oppositely modulate psychostimulant action and DARPP-32 phosphorylation.

    Directory of Open Access Journals (Sweden)

    Hai-Ying Shen

    Full Text Available Adenosine A2A receptors (A2AR are located postsynaptically in striatopallidal GABAergic neurons, antagonizing dopamine D2 receptor functions, and are also located presynaptically at corticostriatal terminals, facilitating glutamate release. To address the hypothesis that these two A2AR populations differently control the action of psychostimulants, we characterized A2AR modulation of cocaine-induced effects at the level of DARPP-32 phosphorylation at Thr-34 and Thr-75, c-Fos expression, and psychomotor activity using two lines of cell-type selective A2AR knockout (KO mice with selective A2AR deletion in GABAergic neurons (striatum-A2AR-KO mice, or with A2AR deletion in both striatal GABAergic neurons and projecting cortical glutamatergic neurons (forebrain-A2AR-KO mice. We demonstrated that striatum-A2AR KO mice lacked A2ARs exclusively in striatal GABAergic terminals whereas forebrain-A2AR KO mice lacked A2ARs in both striatal GABAergic and glutamatergic terminals leading to a blunted A2AR-mediated facilitation of synaptosomal glutamate release. The inactivation of A2ARs in GABAergic neurons reduced striatal DARPP-32 phosphorylation at Thr-34 and increased its phosphorylation at Thr-75. Conversely, the additional deletion of corticostriatal glutamatergic A2ARs produced opposite effects on DARPP-32 phosphorylation at Thr-34 and Thr-75. This distinct modulation of DARPP-32 phosphorylation was associated with opposite responses to cocaine-induced striatal c-Fos expression and psychomotor activity in striatum-A2AR KO (enhanced and forebrain-A2AR KO mice (reduced. Thus, A2ARs in glutamatergic corticostriatal terminals and in GABAergic striatal neurons modulate the action of psychostimulants and DARPP-32 phosphorylation in opposite ways. We conclude that A2ARs in glutamatergic terminals prominently control the action of psychostimulants and define a novel mechanism by which A2ARs fine-tune striatal activity by integrating GABAergic, dopaminergic and

  8. Winning hearts and minds in the Namibian border war | de Visser ...

    African Journals Online (AJOL)

    During the Namibian border war, South African counterinsurgency doctrine acknowledged the importance of securing the allegiance and cooperation of the population. This article demonstrates that, in the operational zone, the responsibility of winning the hearts and minds of the Namibian people largely fell to the SADF ...

  9. Synthesis of [3H]WIN 35,065-2; a new radioligand for cocaine receptors

    International Nuclear Information System (INIS)

    Naseree, T.M.; Abraham, P.; Kepler, J.A.; Carroll, F.I.; Lewin, A.H.; Kuhar, M.J.

    1990-01-01

    Treatment of methyl (-)-3β-phenylnortropane-2β-carboxylate with [ 3 H]CH 3 I afforded [ 3 H]WIN 35,065-2 with specific activity of 25 Ci/mmol, a new ligand for the cocaine recognition site. (author)

  10. Windows Calorimeter Control (WinCal) program computer software configuration management plan

    International Nuclear Information System (INIS)

    1997-01-01

    This document describes the system configuration management activities performed in support of the Windows Calorimeter Control (WinCal) system, in accordance with Site procedures based on Institute of Electrical and Electronic Engineers (IEEE) Standard 828-1990, Standard for Software Configuration Management Plans (IEEE 1990) and IEEE Standard 1042-1987, Guide to Software Configuration Management (IEEE 1987)

  11. WinGraphics: An optimized windowing environment for interactive real-time simulations

    International Nuclear Information System (INIS)

    Verboncoeur, J.P.; Vahedi, V.

    1989-01-01

    We have developed a customized windowing environment, Win Graphics, which provides particle simulation codes with an interactive user interface. The environment supports real-time animation of the simulation, displaying multiple diagnostics as they evolve in time. In addition, keyboard and printer (PostScript and dot matrix) support is provided. This paper describes this environment

  12. At Issue: An Award-Winning Community College Instructor's Approach to Teaching and Learning

    Science.gov (United States)

    Welsh, Hilarie B.

    2015-01-01

    The author presents themes that were identified from a case study that focused on the instructional practices of an award-winning community college composition/literature teacher. The themes for this case study focus on the importance of student-centered learning which involve: (1) writing peer response strategies; (2) student engagement in using…

  13. Analysing the Subject of Peace in Award-Winning Children's and Adolescent Novels in Turkey

    Science.gov (United States)

    Aslan, Canan; Kepenekci, Yasemin Karaman; Güldenoglu, Bilge Nur Dogan; Karagül, Sedat

    2016-01-01

    The purpose of this study is to reveal how the concept of peace is addressed in the national award-winning novels written for secondary school students within the Republic of Turkey. Data for this study was obtained from child and youth literature award organizations, associations and publishers within Turkey. Each group which was researched has…

  14. Many Libraries Have Gone to Federated Searching to Win Users Back from Google. Is It Working?

    Science.gov (United States)

    King, Douglas

    2008-01-01

    In the last issue, this journal asked a question on many librarians' minds, and it was pleased with the depth and variety of responses. As suggested by this journal editorial board member Oliver Pesch, readers were asked, "Many libraries have gone to federated searching to win users back from Google. Is it working?" Respondents approached the…

  15. Which skills and factors better predict winning and losing in high-level men's volleyball?

    Science.gov (United States)

    Peña, Javier; Rodríguez-Guerra, Jorge; Buscà, Bernat; Serra, Núria

    2013-09-01

    The aim of this study was to determine which skills and factors better predicted the outcomes of regular season volleyball matches in the Spanish "Superliga" and were significant for obtaining positive results in the game. The study sample consisted of 125 matches played during the 2010-11 Spanish men's first division volleyball championship. Matches were played by 12 teams composed of 148 players from 17 different nations from October 2010 to March 2011. The variables analyzed were the result of the game, team category, home/away court factors, points obtained in the break point phase, number of service errors, number of service aces, number of reception errors, percentage of positive receptions, percentage of perfect receptions, reception efficiency, number of attack errors, number of blocked attacks, attack points, percentage of attack points, attack efficiency, and number of blocks performed by both teams participating in the match. The results showed that the variables of team category, points obtained in the break point phase, number of reception errors, and number of blocked attacks by the opponent were significant predictors of winning or losing the matches. Odds ratios indicated that the odds of winning a volleyball match were 6.7 times greater for the teams belonging to higher rankings and that every additional point in Complex II increased the odds of winning a match by 1.5 times. Every reception and blocked ball error decreased the possibility of winning by 0.6 and 0.7 times, respectively.

  16. Deploying the Win TR-20 computational engine as a web service

    Science.gov (United States)

    Despite its simplicity and limitations, the runoff curve number method remains a widely-used hydrologic modeling tool, and its use through the USDA Natural Resources Conservation Service (NRCS) computer application WinTR-20 is expected to continue for the foreseeable future. To facilitate timely up...

  17. Portraits of Learning 2007: We Present This Year's Winning Student Photos

    Science.gov (United States)

    Technology & Learning, 2007

    2007-01-01

    This year's more than 4,000 Portraits of Learning entries attest to the growing comfort with digital technologies and visual arts that today's kids have. This article presents 12 winning student photos of the Portraits of Learning 2007. The winners emerged from the selection of subjects that varied wildly--from grasshoppers, giraffes, zebras, and…

  18. Firms vie to offer DOE a prize-winning recipe for cleanup

    Energy Technology Data Exchange (ETDEWEB)

    Powers, M.B.

    1994-04-25

    Eager to get the most bang for its waste cleanup bucks, the US Department of Energy is conducting its own version of the Pillsbury bake-off. DOE is pitting two environmental contractors, Rust International Corp. and Lockheed Environmental Systems and Technologies Co., against each other to come up with the prize-winning recipe for cleaning up some nasty waste problems.

  19. Winning in NCAA Women?s Soccer: Does the Gender of the Coach Matter?

    Science.gov (United States)

    Brush, Brian C.; Naples, Gregory J.

    2011-01-01

    While women's intercollegiate soccer has grown rapidly over the past three decades, men still hold nearly two-thirds of all head coaching positions in NCAA Division I women's soccer programs. This paper explores whether the gender of the head coach affects success in winning games. After considering various reasons why gender might matter, we…

  20. WiN Argentina: Re Launch of National Chapter and New Activities

    International Nuclear Information System (INIS)

    Sayan, J.; Gervasoni, J.; Cantargi, F.; Cintas, A.; Garea, V.

    2015-01-01

    Women of the Argentinian Nuclear Sector have shared WiN Global’s vision since its birth in 1992. Many have become active members and participated in its Annual Conferences, by presenting papers or country reports (Sweden, 1995 and Russia 1996, Taiwan 1998). Due to several drastic changes in the Sector, such as projects cancellations and reduction of personnel, occurred during the late 1990’s, the National Chapter reduced its activities. Thanks to the restless work of its founder, Dr. Maela Viirsoo, and a group of new Members, the Chapter has been recently re-launched at the 40th Annual Meeting of the Argentinian Nuclear Technology Association (AATN) and new adherents have represented the country in last year’s WiN Global Annual Conference held in Australia. In this presentation, we will show our new membership and governing structure in order to fulfill the WiN Charter’s obligations and WiN Global “Rules and Procedures”. We will also present the planned activities to promote the benefits of nuclear technologies from women’s perspective. Professional women working in several nuclear fields, such as: science and technology, health, cultural, educational and social will improve the community perception towards nuclear technology by organizing lectures, exchanging ideas and stimulating joint initiatives in the educational local system. (author)

  1. A Descriptive-Analytic Study of the Practice Field Behavior of a Winning Female Coach.

    Science.gov (United States)

    Dodds, Patt; Rife, Frank

    A winning collegiate field hockey coach was observed across seventeen practice sessions through one complete competitive season. A category system for the event recording of verbal and nonverbal behaviors delivered to the team and to the sixteen individual players produced descriptive-analytic information about relative behavior frequencies for…

  2. Prepare for X-Win32 - the new X11 server software for Windows computers

    CERN Multimedia

    IT Department

    2011-01-01

    Starnet X-Win32 will replace Exceed as the X11 Server software on Windows computers by February 2012. X11 Server software allows a Windows user to have a graphical user interface on a remote Linux server. This change, initially motivated by a significant change of license conditions for Exceed, brings an easier integration of Windows and Linux logon mechanisms. At the same time, X-Win32 addresses the common use cases while providing a more intuitive configuration interface. CERN Predefined Connections will be available as before. They offer an easy way of starting applications on LXPLUS using PuTTY or starting the KDE, GNOME or ICE window managers. Since X-Win32 is better integrated with SSH and CERN Kerberos compared to Exceed, it is much simpler to set up secure access to Linux services. The decision to choose X-Win32 as the new X11 software resulted from an evaluation that involved various user communities and support teams. More information, including the documented use cases, is available at https://...

  3. Investigation of the effect of AtWIN1/SHN1 overexpression on poplar trees

    Science.gov (United States)

    Shaneka S.  Lawson

    2016-01-01

    Background: Interactions between plants and the environment occur primarily at the leaf level. The plant cuticle consists of a menagerie of lipids, waxes and polymers merging to form an insoluble membrane to protect plant leaves from contamination. In Arabidopsis, wax Inducer1/shine1 (WIN1/SHN1) and its family members have demonstrated roles in wax...

  4. Winning in the Rural Zone: How Cam Henderson Invented the Zone Defense.

    Science.gov (United States)

    Barnett, Bob

    1992-01-01

    Assesses the distinguished coaching career of Cam Henderson, who won over 611 games in 36 seasons of college basketball and coached over 151 college football wins at West Virginia colleges, mainly at Marshall University (Huntington). His influence has been so pervasive that Marshall University's basketball arena is named in his honor. (LP)

  5. 'No Win, No Fee', Cost-Shifting and the Costs of Civil Litigation

    DEFF Research Database (Denmark)

    Fenn, Paul; Grembi, Veronica; Rickman, Neil

    Expenditure on legal services has been rising for much of the last two decades and has attracted considerable policy attention in the UK. We argue that an important reason for this increase lies within the introduction of 'no win no fee' schemes in 1995 and a subsequent amendment which allowed...

  6. John Bardeen: The Only Person to Win Two Nobel Prizes in Physics

    Science.gov (United States)

    Hoddeson, L.

    2011-01-01

    John Bardeen worked on the theory of solids throughout his physics career, winning two Nobel Prizes: the first in 1956 for the invention of the transistor with Walter Brattain and William Shockley; and the second in 1972 for the development with Leon Cooper and J Robert Schrieffer of the Bardeen-Cooper-Schrieffer (BCS) theory of superconductivity.…

  7. An Analysis of Unassigned Recipients/Registrants in the WIN Program. Final Report.

    Science.gov (United States)

    Anderson, Robert

    A study was performed to determine (1) the characteristics of unassigned recipients in the Work Incentive (WIN) program; (2) what services are currently being offered to this group and what services they need to increase their employment potential; (3) the amount of time they spend in this status and the frequency of their movement in and out of…

  8. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    International Nuclear Information System (INIS)

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina; Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya; Pessoa-Pureur, Regina

    2014-01-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to 32 P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca 2+ /calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca 2+ quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca 2+ influx through voltage-dependent Ca 2+ channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative disorders. - Highlights:

  9. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil); Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya [Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil)

    2014-04-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to {sup 32}P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca{sup 2+}/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca{sup 2+} quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca{sup 2+} influx through voltage-dependent Ca{sup 2+} channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative

  10. Transfer after Dual n-Back Training Depends on Striatal Activation Change.

    Science.gov (United States)

    Salminen, Tiina; Kühn, Simone; Frensch, Peter A; Schubert, Torsten

    2016-09-28

    The dual n-back working memory (WM) training paradigm (comprising auditory and visual stimuli) has gained much attention since studies have shown widespread transfer effects. By including a multimodal dual-task component, the task is demanding to the human cognitive system. We investigated whether dual n-back training improves general cognitive resources or a task-specific WM updating process in participants. We expected: (1) widespread transfer effects and the recruitment of a common neuronal network by the training and the transfer tasks and (2) narrower transfer results and that a common activation network alone would not produce transfer, but instead an activation focus on the striatum, which is associated with WM updating processes. The training group showed transfer to an untrained dual-modality WM updating task, but not to single-task versions of the training or the transfer task. They also showed diminished neuronal overlap between the training and the transfer task from pretest to posttest and an increase in striatal activation in both tasks. Furthermore, we found an association between the striatal activation increase and behavioral improvement. The control groups showed no transfer and no change in the amount of activation overlap or in striatal activation from pretest to posttest. We conclude that, instead of improving general cognitive resources (which would have required a transfer effect to all transfer tasks and that a frontal activation overlap between the tasks produced transfer), dual n-back training improved a task-specific process: WM updating of stimuli from two modalities. The current study allows for a better understanding of the cognitive and neural effects of working memory (WM) training and transfer. It shows that dual n-back training mainly improves specific processes of WM updating, and this improvement leads to narrow transfer effects to tasks involving the same processes. On a neuronal level this is accompanied by increased neural

  11. Delta FosB and AP-1-mediated transcription modulate cannabinoid CB₁ receptor signaling and desensitization in striatal and limbic brain regions.

    Science.gov (United States)

    Lazenka, Matthew F; David, Bethany G; Lichtman, Aron H; Nestler, Eric J; Selley, Dana E; Sim-Selley, Laura J

    2014-10-01

    Repeated Δ(9)-tetrahydrocannabinol (THC) administration produces cannabinoid type 1 receptor (CB₁R) desensitization and downregulation, as well as tolerance to its in vivo pharmacological effects. However, the magnitude of CB₁R desensitization varies by brain region, with CB₁Rs in the striatum and its output nuclei undergoing less desensitization than other regions. A growing body of data indicates that regional differences in CB₁R desensitization are produced, in part, by THC-mediated induction of the stable transcription factor, ΔFosB, and subsequent regulation of CB₁Rs. The purpose of the present study was to determine whether THC-mediated induction of ΔFosB in the striatum inhibits CB₁R desensitization in the striatum and output nuclei. This hypothesis was tested using bitransgenic mice with inducible expression of ΔFosB or ΔcJun, a dominant negative inhibitor of AP-1-mediated transcription, in specific forebrain regions. Mice were treated repeatedly with escalating doses of THC or vehicle for 6.5 days, and CB₁R-mediated G-protein activation was assessed using CP55,940-stimulated [(35)S]GTPγS autoradiography. Overexpression of ΔFosB in striatal dopamine type 1 receptor-containing (D1R) medium spiny neurons (MSNs) attenuated CB₁R desensitization in the substantia nigra, ventral tegmental area (VTA) and amygdala. Expression of ΔcJun in striatal D1R- and dopamine type 2 receptor (D2R)-containing MSNs enhanced CB₁R desensitization in the caudate-putamen and attenuated desensitization in the hippocampus and VTA. THC-mediated in vivo pharmacological effects were then assessed in ΔcJun-expressing mice. Tolerance to THC-mediated hypomotility was enhanced in ΔcJun-expressing mice. These data reveal that ΔFosB and possibly other AP-1 binding proteins regulate CB₁R signaling and adaptation in the striatum and limbic system. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. The clinical benefit of imaging striatal dopamine transporters with [123I]FP-CIT SPET in differentiating patients with presynaptic parkinsonism from those with other forms of parkinsonism

    International Nuclear Information System (INIS)

    Booij, J.; Speelman, J.DE.; Horstink, M. W.I.M.; Wolters, E.C.

    2001-01-01

    [ 123 I]FP-CIT (N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane) has been developed successfully as a radioligand for single-photon emission tomography (SPET) imaging of dopamine transporters, which are situated in the membrane of dopaminergic neurons. Imaging of these transporters has shown promise as a clinical tool to detect degeneration of the dopaminergic nigrostriatal pathway. Several ''presynaptic parkinsonian'' syndromes, such as Parkinson's disease or multiple system atrophy, are characterised by degeneration of the nigrostriatal pathway. [ 123 I]FP-CIT SPET imaging studies have shown the ability to detect loss of striatal dopamine transporters in such syndromes. However, in clinical practice it is sometimes difficult, but important, to discriminate patients with ''presynaptic parkinsonism'' from those with other forms of parkinsonism not characterised by loss of presynaptic dopaminergic cells (e.g. psychogenic parkinsonism or drug-induced postsynaptic parkinsonism). In these inconclusive cases, it may be of value to confirm or exclude the existence of degeneration of nigrostriatal dopaminergic cells by using imaging techniques such as [ 123 I]FP-CIT SPET. Using [ 123 I]FP-CIT SPET, we have imaged the striatal dopamine transporters in a group of patients with inconclusive forms of parkinsonism, and, moreover, have been able to perform clinical follow-up of these patients 2-4 years after imaging. In 33 inconclusive cases, ratios of specific to non-specific binding were calculated for the caudate nucleus and putamen following [ 123 I]FP-CIT SPET imaging and compared with ratios obtained in healthy controls. In nine of the patients, degeneration of the nigrostriatal pathway was found scintigraphically and in all these cases, presynaptic parkinsonism was confirmed by clinical follow-up. In the other 24 subjects no degeneration was found scintigraphically. Forms of parkinsonism other than the presynaptic were confirmed at follow-up in 19 cases

  13. Winning in sequential Parrondo games by players with short-term memory

    Science.gov (United States)

    Cheung, K. W.; Ma, H. F.; Wu, D.; Lui, G. C.; Szeto, K. Y.

    2016-05-01

    The original Parrondo game, denoted as AB3, contains two independent games: A and B. The winning or losing of games A and B is defined by the change of one unit of capital. Game A is a losing game if played continuously, with winning probability p=0.5-ε , where ε =0.003 . Game B is also losing and has two coins: a good coin with winning probability {{p}\\text{g}}=0.75-ε is used if the player’s capital is not divisible by 3, otherwise a bad coin with winning probability {{p}\\text{b}}=0.1-ε is used. The Parrondo paradox refers to the situation where the mixture of games A and B in a sequence leads to winning in the long run. The paradox can be resolved using Markov chain analysis. We extend this setting of the Parrondo game to involve players with one-step memory. The player can win by switching his choice of A or B game in a Parrondo game sequence. If the player knows the identity of the game he plays and the state of his capital, then the player can win maximally. On the other hand, if the player does not know the nature of the game, then he is playing a (C, D) game, where either (C  =  A, D  =  B), or (C  =  B, D  =  A). For a player with one-step memory playing the AB3 game, he can achieve the highest expected gain with switching probability equal to 3/4 in the (C, D) game sequence. This result has been found first numerically and then proven analytically. Generalization to an AB mod(M) Parrondo game for other integers M has been made for the general domain of parameters {{p}\\text{b}}\\text{A}}capital is even, or the initial game is B and the initial capital is odd. There is still a possibility of the Parrondo effect for the other two cases when M is even: the initial game is A and the initial capital is odd, or the initial game is B and the initial capital is even. These observations from numerical experiments can be understood as the factorization of the Markov chains into two distinct cycles. Discussion of these effects

  14. Astronomers Win Protection for Key Part of Radio Spectrum

    Science.gov (United States)

    2000-06-01

    International Telecommunication Union meet to painstakingly parcel out the radio frequency spectrum between radio-based applications such as personal communications, satellite broadcasting, GPS and amateur radio, and the sciences of radio astronomy, earth exploration and deep space research. The WRC also coordinates sharing between services in the same radio bands. WRC decisions are incorporated into the Radio Regulations that govern radio services worldwide. The new spectrum allocations for radio astronomy are the first since 1979. Millimeter-wave astronomy was then in its infancy and many of its needs were not yet known. As astronomers began to explore this region of the spectrum they found spectral lines from many interesting molecules in space. Many of those lines had not fallen into the areas originally set aside for astronomy, but most will be under the new allocations. "It's a win for millimeter-wave science," said Dr. John Whiteoak of the Australia Telescope National Facility, Australian delegate to WRC-00. "This secures its future." The protection is a significant step for both existing millimeter-wave telescopes and new ones such as the Atacama Large Millimeter Array (ALMA) now being planned by a U.S.-European consortium. Even at its isolated site in Chile's Atacama desert, ALMA would be vulnerable to interference from satellite emissions. Sensitive radio astronomy receivers are blinded by these emissions, just as an optical telescope would be by a searchlight. "There is more energy at millimeter and sub-millimeter wavelengths washing through the Universe than there is of light or any other kind of radiation," said ALMA Project Scientist, Dr. Al Wootten of the National Radio Astronomy Observatory. "Imaging the sources of this energy can tell us a great deal about the formation of stars and galaxies, and even planets." "But the Earth's atmosphere isn't very kind to us - it has only a few windows at these frequencies, and not very transparent ones at that. They are

  15. Reduced frontal cortical thickness and increased caudate volume within fronto-striatal circuits in young adult smokers.

    Science.gov (United States)

    Li, Yangding; Yuan, Kai; Cai, Chenxi; Feng, Dan; Yin, Junsen; Bi, Yanzhi; Shi, Sha; Yu, Dahua; Jin, Chenwang; von Deneen, Karen M; Qin, Wei; Tian, Jie

    2015-06-01

    Smoking during early adulthood results in neurophysiological and brain structural changes that may promote nicotine dependence later in life. Previous studies have revealed the important roles of fronto-striatal circuits in the pathology of nicotine dependence; however, few studies have focused on both cortical thickness and subcortical striatal volume differences between young adult smokers and nonsmokers. Twenty-seven young male adult smokers and 22 age-, education- and gender-matched nonsmokers were recruited in the present study. The cortical thickness and striatal volume differences of young adult smokers and age-matched nonsmokers were investigated in the present study and then correlated with pack-years and Fagerström Test for Nicotine Dependence (FTND). The following results were obtained: (1) young adult smokers showed significant cortical thinning in the frontal cortex (left caudal anterior cingulate cortex (ACC), right lateral orbitofrontal cortex (OFC)), left insula, left middle temporal gyrus, right inferior parietal lobule, and right parahippocampus; (2) in regards to subcortical striatal volume, the volume of the right caudate was larger in young adult smokers than nonsmokers; and (3) the cortical thickness of the right dorsolateral prefrontal cortex (DLPFC) and OFC were associated with nicotine dependence severity (FTND) and cumulative amount of nicotine intake (pack-years) in smokers, respectively. This study revealed reduced frontal cortical thickness and increased caudate volume in the fronto-striatal circuits in young adult smokers compared to nonsmokers. These deficits suggest an imbalance between cognitive control (reduced protection factors) and reward drive behaviours (increased risk factors) associated with nicotine addiction and relapse. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Differences in number and distribution of striatal calbindin medium spiny neurons between a vocal-learner (Melopsittacus undulatus and a non-vocal learner bird (Colinus virginianus

    Directory of Open Access Journals (Sweden)

    Elena eGarcia-Calero

    2013-12-01

    Full Text Available Striatal projecting neurons, known as medium spiny neurons (MSNs, segregate into two compartments called matrix and striosome in the mammalian striatum. The matrix domain is characterized by the presence of calbindin immunopositive (CB+ MSNs, not observed in the striosome subdivision. The existence of a similar CB+ MSN population has recently been described in two striatal structures in male zebra finch (a vocal learner bird: the striatal capsule and the Area X, a nucleus implicated in song learning. Female zebra finches show a similar pattern of CB+ MSNs than males in the developing striatum but loose these cells in juveniles and adult stages. In the present work we analyzed the existence and allocation of CB+MSNs in the striatal domain of the vocal learner bird budgerigar (representative of psittaciformes order and the non-vocal learner bird quail (representative of galliformes order. We studied the co-localization of CB protein with FoxP1, a transcription factor expressed in vertebrate striatal MSNs. We observed CB+ MSNs in the medial striatal domain of adult male and female budgerigars, although this cell type was missing in the potentially homologous nucleus for Area X in budgerigar. In quail, we observed CB+ cells in the striatal domain at developmental and adult stages but they did not co-localize with the MSN marker FoxP1. We also described the existence of the CB+ striatal capsule in budgerigar and quail and compared these results with the CB+ striatal capsule observed in juvenile zebra finches. Together, these results point out important differences in CB+MSN distribution between two representative species of vocal learner and non-vocal learner avian orders (respectively the budgerigar and the quail, but also between close vocal learner bird families.

  17. Systems Genetic Analyses Highlight a TGFβ-FOXO3 Dependent Striatal Astrocyte Network Conserved across Species and Associated with Stress, Sleep, and Huntington's Disease.

    Science.gov (United States)

    Scarpa, Joseph R; Jiang, Peng; Losic, Bojan; Readhead, Ben; Gao, Vance D; Dudley, Joel T; Vitaterna, Martha H; Turek, Fred W; Kasarskis, Andrew

    2016-07-01

    Recent systems-based analyses have demonstrated that sleep and stress traits emerge from shared genetic and transcriptional networks, and clinical work has elucidated the emergence of sleep dysfunction and stress susceptibility as early symptoms of Huntington's disease. Understanding the biological bases of these early non-motor symptoms may reveal therapeutic targets that prevent disease onset or slow disease progression, but the molecular mechanisms underlying this complex clinical presentation remain largely unknown. In the present work, we specifically examine the relationship between these psychiatric traits and Huntington's disease (HD) by identifying striatal transcriptional networks shared by HD, stress, and sleep phenotypes. First, we utilize a systems-based approach to examine a large publicly available human transcriptomic dataset for HD (GSE3790 from GEO) in a novel way. We use weighted gene coexpression network analysis and differential connectivity analyses to identify transcriptional networks dysregulated in HD, and we use an unbiased ranking scheme that leverages both gene- and network-level information to identify a novel astrocyte-specific network as most relevant to HD caudate. We validate this result in an independent HD cohort. Next, we computationally predict FOXO3 as a regulator of this network, and use multiple publicly available in vitro and in vivo experimental datasets to validate that this astrocyte HD network is downstream of a signaling pathway important in adult neurogenesis (TGFβ-FOXO3). We also map this HD-relevant caudate subnetwork to striatal transcriptional networks in a large (n = 100) chronically stressed (B6xA/J)F2 mouse population that has been extensively phenotyped (328 stress- and sleep-related measurements), and we show that this striatal astrocyte network is correlated to sleep and stress traits, many of which are known to be altered in HD cohorts. We identify causal regulators of this network through Bayesian network

  18. Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo

    DEFF Research Database (Denmark)

    Kolko, M; Bruhn, T; Christensen, Thomas

    1999-01-01

    The secretory phospholipases A2 (sPLA2) OS2 (10, 20 and 50 pmol) or OS1, (50 pmol) purified from taipan snake Oxyuranus scutellatus scutellatus venom, and the excitatory amino acid glutamate (Glu) (2.5 and 5.0 micromol) were injected into the right striatum of male Wistar rats. Injection of 10...... no tissue damage or neurological abnormality. After injection of 5.0 micromol Glu, the animals initially circled towards the side of injection, and gradually developed generalized clonic convulsions. These animals showed a well demarcated striatal infarct. When non-toxic concentrations of 20 pmol OS2 and 2.......5 micromol Glu were co-injected, a synergistic neurotoxicity was observed. Extensive histological damage occurred in the entire right hemisphere, and in several rats comprising part of the contralateral hemisphere. These animals were apathetic in the immediate hours following injection, with circling towards...

  19. Reappraising striatal D1- and D2-neurons in reward and aversion.

    Science.gov (United States)

    Soares-Cunha, Carina; Coimbra, Barbara; Sousa, Nuno; Rodrigues, Ana J

    2016-09-01

    The striatum has been involved in complex behaviors such as motor control, learning, decision-making, reward and aversion. The striatum is mainly composed of medium spiny neurons (MSNs), typically divided into those expressing dopamine receptor D1, forming the so-called direct pathway, and those expressing D2 receptor (indirect pathway). For decades it has been proposed that these two populations exhibit opposing control over motor output, and recently, the same dichotomy has been proposed for valenced behaviors. Whereas D1-MSNs mediate reinforcement and reward, D2-MSNs have been associated with punishment and aversion. In this review we will discuss pharmacological, genetic and optogenetic studies that indicate that there is still controversy to what concerns the role of striatal D1- and D2-MSNs in this type of behaviors, highlighting the need to reconsider the early view that they mediate solely opposing aspects of valenced behaviour. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior.

    Science.gov (United States)

    O'Hare, Justin K; Li, Haofang; Kim, Namsoo; Gaidis, Erin; Ade, Kristen; Beck, Jeff; Yin, Henry; Calakos, Nicole

    2017-09-05

    Habit formation is a behavioral adaptation that automates routine actions. Habitual behavior correlates with broad reconfigurations of dorsolateral striatal (DLS) circuit properties that increase gain and shift pathway timing. The mechanism(s) for these circuit adaptations are unknown and could be responsible for habitual behavior. Here we find that a single class of interneuron, fast-spiking interneurons (FSIs), modulates all of these habit-predictive properties. Consistent with a role in habits, FSIs are more excitable in habitual mice compared to goal-directed and acute chemogenetic inhibition of FSIs in DLS prevents the expression of habitual lever pressing. In vivo recordings further reveal a previously unappreciated selective modulation of SPNs based on their firing patterns; FSIs inhibit most SPNs but paradoxically promote the activity of a subset displaying high fractions of gamma-frequency spiking. These results establish a microcircuit mechanism for habits and provide a new example of how interneurons mediate experience-dependent behavior.

  1. Reduced Levels of Proteasome Products in a Mouse Striatal Cell Model of Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Sayani Dasgupta

    Full Text Available Huntington's disease is the result of a long polyglutamine tract in the gene encoding huntingtin protein, which in turn causes a large number of cellular changes and ultimately results in neurodegeneration of striatal neurons. Although many theories have been proposed, the precise mechanism by which the polyglutamine expansion causes cellular changes is not certain. Some evidence supports the hypothesis that the long polyglutamine tract inhibits the proteasome, a multiprotein complex involved in protein degradation. However, other studies report normal proteasome function in cells expressing long polyglutamine tracts. The controversy may be due to the methods used to examine proteasome activity in each of the previous studies. In the present study, we measured proteasome function by examining levels of endogenous peptides that are products of proteasome cleavage. Peptide levels were compared among mouse striatal cell lines expressing either 7 glutamines (STHdhQ7/Q7 or 111 glutamines in the huntingtin protein, either heterozygous (STHdhQ7/Q111 or homozygous (STHdhQ111/Q111. Both of the cell lines expressing huntingtin with 111 glutamines showed a large reduction in nearly all of the peptides detected in the cells, relative to levels of these peptides in cells homozygous for 7 glutamines. Treatment of STHdhQ7/Q7 cells with proteasome inhibitors epoxomicin or bortezomib also caused a large reduction in most of these peptides, suggesting that they are products of proteasome-mediated cleavage of cellular proteins. Taken together, these results support the hypothesis that proteasome function is impaired by the expression of huntingtin protein containing long polyglutamine tracts.

  2. Decreased firing of striatal neurons related to licking during acquisition and overtraining of a licking task.

    Science.gov (United States)

    Tang, Chris C; Root, David H; Duke, Dawn C; Zhu, Yun; Teixeria, Kate; Ma, Sisi; Barker, David J; West, Mark O

    2009-11-04

    Neurons that fire in relation to licking, in the ventral part of the dorsolateral striatum (DLS), were studied during acquisition and performance of a licking task in rats for 14 sessions (2 h/d). Task learning was indicated by fewer errors of omission of licking and improved movement efficiency (i.e., shorter lick duration) over sessions. Number of licks did not change over sessions. Overtraining did not result in habit formation, as indicated by similar reductions of licking responses following devaluation by satiety in both early and late sessions. Twenty-nine lick neurons recorded and tracked over sessions exhibited a significant linear decrease in average firing rate across all neurons over sessions, correlating with concurrent declines in lick duration. Individually, most neurons (86%) exhibited decreased firing rates, while a small proportion (14%) exhibited increased firing rates, during lick movements that were matched over sessions. Reward manipulations did not alter firing patterns over sessions. Aside from the absence of habit formation, striatal processing during unconditioned movements (i.e., licking) was characterized by high activity of movement-related neurons during early performance and decreased activity of the same neurons during overtraining, similar to our previous report of head movement neurons during acquired, skilled, instrumental head movements that ultimately became habitual (Tang et al., 2007). Decreased activity in DLS neurons may reflect a common neural mechanism underlying improvement in movement efficiency with overtraining. Nonetheless, the decreased striatal firing in relation to a movement that did not become habitual demonstrates that not all DLS changes reflect habit formation.

  3. Pergolide inhibition of calcium-induced 3H-dopamine release from striatal synaptosomes

    International Nuclear Information System (INIS)

    Bowyer, J.F.; Weiner, N.

    1986-01-01

    Several investigators have reported that dopamine agonists or antagonists are unable to modulate the K + -evoked release of 3 H-dopamine ( 3 H-DA) from striatal synaptosomes. To further assess the role of DA in regulating its release, they have examined the effects of pergolide on Ca ++ (1.25 mM)-evoked release of 3 H-DA from partially K + -depolarized striatal synaptosomes. Synaptosomes (P2 pellet) were isolated from rat striatum and incubated for 5 min at 37 0 C in a Ca ++ -free Krebs-Ringer buffer containing 25 nM 3 H-DA. After radiolabeling, the synaptosomes were superfused for 12 min with Ca ++ -free 6 mM Krebs-Ringer buffer to determine basal release of 3 H-DA. Synaptosomes were then exposed to test drugs for 8 min prior to Ca ++ challenge. Ca ++ addition resulted in a 3-fold increase in 3 H-DA release within 2-4 min. Pergolide inhibited the release of 3 H-DA in a concentration-dependent manner. Release was inhibited to 56% of control by 10 nM pergolide. This was largely reversed by 0.1 μM S-sulpiride. Ca ++ -evoked release was inhibited over 70% by 1 μM tetrodotoxin (TTX), indicating that voltage-dependent Na + channels may play a role in the release process. The combination of pergolide and TTX inhibited release to a degree similar to TTX alone. These results suggest that pergolide may inhibit 3 H-DA release by a TTX-sensitive mechanism and that the dopaminergic autoreceptors may be linked to voltage-sensitive Na + channels

  4. Cortical-striatal gene expression in neonatal hippocampal lesion (NVHL)-amplified cocaine sensitization.

    Science.gov (United States)

    Chambers, R A; McClintick, J N; Sentir, A M; Berg, S A; Runyan, M; Choi, K H; Edenberg, H J

    2013-07-01

    Cortical-striatal circuit dysfunction in mental illness may enhance addiction vulnerability. Neonatal ventral hippocampal lesions (NVHL) model this dual diagnosis causality by producing a schizophrenia syndrome with enhanced responsiveness to addictive drugs. Rat genome-wide microarrays containing >24 000 probesets were used to examine separate and co-occurring effects of NVHLs and cocaine sensitization (15 mg/kg/day × 5 days) on gene expression within medial prefrontal cortex (MPFC), nucleus accumbens (NAC), and caudate-putamen (CAPU). Two weeks after NVHLs robustly amplified cocaine behavioral sensitization, brains were harvested for genes of interest defined as those altered at P cocaine effects or interactions. Among 135 genes so impacted, NVHLs altered twofold more than cocaine, with half of all changes in the NAC. Although no genes were changed in the same direction by both NVHL and cocaine history, the anatomy and directionality of significant changes suggested synergy on the neural circuit level generative of compounded behavioral phenotypes: NVHL predominantly downregulated expression in MPFC and NAC while NVHL and cocaine history mostly upregulated CAPU expression. From 75 named genes altered by NVHL or cocaine, 27 had expression levels that correlated significantly with degree of behavioral sensitization, including 11 downregulated by NVHL in MPFC/NAC, and 10 upregulated by NVHL or cocaine in CAPU. These findings suggest that structural and functional impoverishment of prefrontal-cortical-accumbens circuits in mental illness is associated with abnormal striatal plasticity compounding with that in addictive disease. Polygenetic interactions impacting neuronal signaling and morphology within these networks likely contribute to addiction vulnerability in mental illness. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  5. Increased impulsivity retards the transition to dorsolateral striatal dopamine control of cocaine seeking.

    Science.gov (United States)

    Murray, Jennifer E; Dilleen, Ruth; Pelloux, Yann; Economidou, Daina; Dalley, Jeffrey W; Belin, David; Everitt, Barry J

    2014-07-01

    Development of maladaptive drug-seeking habits occurs in conjunction with a ventral-to-dorsal striatal shift in dopaminergic control over behavior. Although these habits readily develop as drug use continues, high impulsivity predicts loss of control over drug seeking and taking. However, whether impulsivity facilitates the transition to dorsolateral striatum (DLS) dopamine-dependent cocaine-seeking habits or whether impulsivity and cocaine-induced intrastriatal shifts are additive processes is unknown. High- and low-impulsive rats identified in the five-choice serial reaction-time task were trained to self-administer cocaine (.25 mg/infusion) with infusions occurring in the presence of a cue-light conditioned stimulus. Dopamine transmission was blocked in the DLS after three stages of training: early, transition, and late-stage, by bilateral intracranial infusions of α-flupenthixol (0, 5, 10, or 15 μg/side) during 15-min cocaine-seeking test sessions in which each response was reinforced by a cocaine-associated conditioned stimulus presentation. In early-stage tests, neither group was affected by DLS dopamine receptor blockade. In transition-stage tests, low-impulsive rats showed a significant dose-dependent reduction in cocaine seeking, whereas high-impulsive rats were still unaffected by α-flupenthixol infusions. In the final, late-stage seeking test, both groups showed dose-dependent sensitivity to dopamine receptor blockade. The results demonstrate that high impulsivity is associated with a delayed transition to DLS-dopamine-dependent control over cocaine seeking. This suggests that, if impulsivity confers an increased propensity to addiction, it is not simply through a more rapid development of habits but instead through interacting corticostriatal and striato-striatal processes that result ultimately in maladaptive drug-seeking habits. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

  6. PET evaluation of the relationship between D2 receptor binding and glucose metabolism in patients with parkinsonism

    International Nuclear Information System (INIS)

    Nakagawa, Makoto; Kuwabara, Yasuo; Taniwaki, Takayuki; Koga, Hirofumi; Kaneko, Koichiro; Hayashi, Kazutaka; Kira, Jun-ichi; Honda, Hiroshi; Sasaki, Masayuki

    2005-01-01

    The objective of this study was to clarify the relationship between D 2 receptor binding and the cerebral metabolic rate for glucose (CMRGlu) in patients with parkinsonism, we simultaneously measured both of these factors, and then compared the results. The subjects consisted of 24 patients: 9 with Parkinson's disease (PD), 3 with Juvenile Parkinson's disease (JPD), 9 with multiple system atrophy (MSA), and 3 with progressive supranuclear palsy (PSP). The striatal D 2 receptor binding was measured by the C-11 raclopride transient equilibrium method. CMRGlu was investigated by the F-18 fluorodeoxyglucose autoradiographic method. The D 2 receptor binding in both the caudate nucleus and putamen showed a positive correlation with the CMRGlu in the PD-JPD group, but the two parameters demonstrated no correlation in the MSA-PSP group. The left/right (L/R) ratio of D 2 receptor binding in the putamen showed a positive correlation with that of CMRGlu in the MSA-PSP group, while the two demonstrated no correlation in the PD-JPD group. Our PET study showed striatal D 2 receptor binding and the CMRGlu to be closely related in patients with parkinsonism, even though the results obtained using the L/R ratios tended to differ substantially from those obtained using absolute values. The reason for this difference is not clear, but this finding may reflect the pathophysiology of these disease entities. (author)

  7. Mazindol analogues as potential inhibitors of the cocaine binding site at the dopamine transporter.

    Science.gov (United States)

    Houlihan, William J; Kelly, Lawrence; Pankuch, Jessica; Koletar, Judith; Brand, Leonard; Janowsky, Aaron; Kopajtic, Theresa A

    2002-09-12

    A series of mazindol (2) and homomazindol (3) analogues with a variety of electron-donating and electron-withdrawing groups in the pendant aryl group and the benzo ring C, as well as H, methoxy, and alkyl groups replacing the hydroxyl group were synthesized, and their binding affinities at the dopamine transporter (DAT) on rat or guinea pig striatal membranes were determined. Several active analogues were also evaluated for their ability to block uptake of DA, 5-HT, and NE and inhibit binding of [(125)I] RTI-55 at HEK-hDAT, HEK-hSERT, and HEK-hNET cells. Mazindane (26) was found to be a pro-drug, oxidizing (5-H --> 5-OH) to mazindol on rat striatal membranes and HEK-hDAT cells. The 4',7,8-trichloro analogue (38) of mazindol was the most potent and selective ligand for HEK-hDAT cells (DAT K(i) = 1.1 nM; SERT/DAT = 1283 and NET/DAT = 38). Experimental results strongly favor the cyclic or ol tautomers of 2 and 3 to bind more tightly at the DAT than the corresponding keto tautomers.

  8. Extrastriatal binding of [{sup 123}I]FP-CIT in the thalamus and pons: gender and age dependencies assessed in a European multicentre database of healthy controls

    Energy Technology Data Exchange (ETDEWEB)

    Koch, Walter; Unterrainer, Marcus; Xiong, Guoming; Bartenstein, Peter [University of Munich, Department of Nuclear Medicine, Munich (Germany); Diemling, Markus [Hermes Medical Solutions, Stockholm (Sweden); Varrone, Andrea [Karolinska University Hospital, Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm (Sweden); Dickson, John C. [UCLH NHS Foundation Trust and University College, Institute of Nuclear Medicine, London (United Kingdom); Tossici-Bolt, Livia [University Hospitals Southampton NHS Trust, Department of Medical Physics, Southampton (United Kingdom); Sera, Terez [University of Szeged, Department of Nuclear Medicine and Euromedic Szeged, Szeged (Hungary); Asenbaum, Susanne [Medical University of Vienna, Department of Neurology, Vienna (Austria); Booij, Jan [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Centre, Amsterdam (Netherlands); Kapucu, Ozlem L. [Gazi University, Department of Nuclear Medicine, Faculty of Medicine, Ankara (Turkey); Kluge, Andreas [ABX-CRO, Dresden (Germany); Ziebell, Morten [Rigshospitalet and University of Copenhagen, Neurobiology Research Unit, Copenhagen (Denmark); Darcourt, Jacques [University of Nice-Sophia Antipolis, Nuclear Medicine Department, Centre Antoine Lacassagne, Nice (France); Nobili, Flavio [University of Genoa, Clinical Neurology Unit, Department of Neuroscience (DINOGMI), Genoa (Italy); Pagani, Marco [CNR, Institute of Cognitive Sciences and Technologies, Rome (Italy); Karolinska Hospital, Department of Nuclear Medicine, Stockholm (Sweden); Hesse, Swen [University of Leipzig, Department of Nuclear Medicine, Leipzig (Germany); Leipzig University Medical Centre, Molecular Neuroimaging IFB Adiposity Diseases, Leipzig (Germany); Borght, Thierry Vander [Universite Catholique de Louvain, Nuclear Medicine Division, CHU Dinant Godinne, Yvoir (Belgium); Laere, Koen van [University Hospital and K.U. Leuven, Nuclear Medicine, Leuven (Belgium); Tatsch, Klaus [Staedtisches Klinikum Karlsruhe, Department of Nuclear Medicine, Karlsruhe (Germany); La Fougere, Christian [University of Munich, Department of Nuclear Medicine, Munich (Germany); University of Tuebingen, Department of Nuclear Medicine, Tuebingen (Germany)

    2014-10-15

    Apart from binding to the dopamine transporter (DAT), [{sup 123}I]FP-CIT shows moderate affinity for the serotonin transporter (SERT), allowing imaging of both monoamine transporters in a single imaging session in different brain areas. The aim of this study was to systematically evaluate extrastriatal binding (predominantly due to SERT) and its age and gender dependencies in a large cohort of healthy controls. SPECT data from 103 healthy controls with well-defined criteria of normality acquired at 13 different imaging centres were analysed for extrastriatal binding using volumes of interest analysis for the thalamus and the pons. Data were examined for gender and age effects as well as for potential influence of striatal DAT radiotracer binding. Thalamic binding was significantly higher than pons binding. Partial correlations showed an influence of putaminal DAT binding on measured binding in the thalamus but not on the pons. Data showed high interindividual variation in extrastriatal binding. Significant gender effects with 31 % higher binding in women than in men were observed in the thalamus, but not in the pons. An age dependency with a decline per decade (±standard error) of 8.2 ± 1.3 % for the thalamus and 6.8 ± 2.9 % for the pons was shown. The potential to evaluate extrastriatal predominant SERT binding in addition to the striatal DAT in a single imaging session was shown using a large database of [{sup 123}I]FP-CIT scans in healthy controls. For both the thalamus and the pons, an age-related decline in radiotracer binding was observed. Gender effects were demonstrated for binding in the thalamus only. As a potential clinical application, the data could be used as a reference to estimate SERT occupancy in addition to nigrostriatal integrity when using [{sup 123}I]FP-CIT for DAT imaging in patients treated with selective serotonin reuptake inhibitors. (orig.)

  9. Multiple [3H]-nemonapride binding sites in calf brain.

    Science.gov (United States)

    Helmeste, D M; Tang, S W; Li, M; Fang, H

    1997-07-01

    [3H]-Nemonapride has been the ligand of choice to label D4 dopamine receptors. Its specificity was questioned when it was discovered that sigma (sigma) sites were also labeled by [3H]-nemonapride. To further characterize the binding of [3H]-nemonapride, three areas of calf brain (striatum, frontal cortex and cerebellum) were examined. In all three areas, [3H]-nemonapride labeled multiple sites. Dopaminergic and sigma sites were the most prominent. The sigma binding profile was sigma-1 like with a Ki binding profile as follows (in order of decreasing potency): haloperidol, PPAP, pentazocine, DTG, U-50488, R(+)-3-PPP. Experiments using sulpiride and pentazocine to block striatal dopaminergic and sigma sites, respectively, revealed additional, not previously characterized binding sites for [3H]-nemonapride. One component which was present in striatum but not in frontal cortex or cerebellum, had affinity for some neuroleptics and WB-4101, but not for typical serotonergic agents. Thus, [3H]-nemonapride has no selectivity for dopamine receptors unless stringent experimental conditions are met.

  10. Suppression of serotonin hyperinnervation does not alter the dysregulatory influences of dopamine depletion on striatal neuropeptide gene expression in rodent neonates.

    Science.gov (United States)

    Basura, G J; Walker, P D

    1999-10-15

    Sixty days following neonatal dopamine depletion (>98%) with 6-hydroxydopamine, preprotachykinin and preprodynorphin mRNA levels were significantly reduced (67 and 78% of vehicle controls, respectively) in the anterior striatum as determined by in situ hybridization while preproenkephalin mRNA expression was elevated (133% of vehicle controls). Suppression of the serotonin hyperinnervation phenomenon in the dopamine-depleted rat with 5,7-dihydroxytryptamine yielded no significant alterations in reduced striatal preprotachykinin (66%) or preprodynorphin (64%) mRNA levels, while preproenkephalin mRNA expression remained significantly elevated (140%). These data suggest that striatal serotonin hyperinnervation does not contribute to the development of dysregulated striatal neuropeptide transmission in either direct or indirect striatal output pathways following neonatal dopamine depletion.

  11. Critical noise can make the minority candidate win: The U.S. presidential election cases

    Science.gov (United States)

    Biswas, Soumyajyoti; Sen, Parongama

    2017-09-01

    A national voting population, when segmented into groups such as, for example, different states, can yield a counterintuitive scenario in which the winner may not necessarily get the highest number of total votes. A recent example is the 2016 presidential election in the United States. We model the situation by using interacting opinion dynamics models, and we look at the effect of coarse graining near the critical points where the spatial fluctuations are high. We establish that the sole effect of coarse graining, which mimics the "winner take all" electoral college system in the United States, can give rise to finite probabilities of events in which a minority candidate wins even in the large size limit near the critical point. The overall probabilities of victory of the minority candidate can be predicted from the models, which indicate that one may expect more instances of minority candidate winning in the future.

  12. Playing the gender card: winning the hearts and minds of the female demographic

    International Nuclear Information System (INIS)

    Brissette, S.

    2006-01-01

    To meet future growth potential, the nuclear industry will have to compete to attract the best and brightest by positioning itself as a viable career choice for women and men of diverse backgrounds considering careers in business, engineering, sciences and the trades. This presentation will showcase the innovative work being undertaken by the Canadian chapter of Women in Nuclear (WiN). Learn more about WiN-Canada's partnership with the CNS aimed at engaging in a dialogue with women opinion leaders in Ontario, the successful international conference hosted by WiN-Canada, the efforts at recognizing and promoting the role of women in our industry with the media, and the results of recent groundbreaking WiN Canada survey on what makes nuclear an appealing career to women in our industry, and what barriers must be overcome to continue to attract women to a career in nuclear in the future. (author)

  13. The effect of uniform color on judging athletes' aggressiveness, fairness, and chance of winning.

    Science.gov (United States)

    Krenn, Bjoern

    2015-04-01

    In the current study we questioned the impact of uniform color in boxing, taekwondo and wrestling. On 18 photos showing two athletes competing, the hue of each uniform was modified to blue, green or red. For each photo, six color conditions were generated (blue-red, blue-green, green-red and vice versa). In three experiments these 108 photos were randomly presented. Participants (N = 210) had to select the athlete that seemed to be more aggressive, fairer or more likely to win the fight. Results revealed that athletes wearing red in boxing and wrestling were judged more aggressive and more likely to win than athletes wearing blue or green uniforms. In addition, athletes wearing green were judged fairer in boxing and wrestling than athletes wearing red. In taekwondo we did not find any significant impact of uniform color. Results suggest that uniform color in combat sports carries specific meanings that affect others' judgments.

  14. Effects of peat-winning on the water environment at a sedge fen ecosystem

    International Nuclear Information System (INIS)

    Lundin, L.

    1996-03-01

    Peatlands are used in agriculture and forestry for vegetational growth and in peat-winning for soil improvement, horticulture production and as fuel. A prerequisite in peatland use is drainage, with influences on water conditions in the peatland and its surroundings. Environmental effects from such peatland use have been investigated at a sedge fen in central Sweden. Groundwater, runoff, water chemistry and stream water biology were studied during almost 14 years. This period started with a virgin undrained peatland, later being drained for forest production and after a period of seven years intensively drained for peat-winning and with peat harvesting going on for another seven years period with hydrological investigations. Results show a lowered groundwater level, increased runoff and both higher concentrations of most elements and higher leaching from the drained peatland. Biomass and number of individuals of the benthic fauna in stream water also increased. 7 refs, 7 figs, 2 tabs

  15. Experience of the WiN Hungary in Communication with Public on a Big Social Events

    International Nuclear Information System (INIS)

    Szucsán, M.

    2015-01-01

    My poster presentation is about a process of communication with public during big social events like festivals, open days and sport’s competitions. The technique is: we make a WiN stand on the frequent place of events, invite visitors and kindly ask them to fill our questionnaire about nuclear industry in Hungary. The questionnaire contents 15 questions about Hungarian NPP (how many units we have, what is electrical output). We communicate with visitors during the filling a questionnaire and after that we check the result. We can see the level of knowledge of our guest and give them the appropriate information on their level. Usually every participant takes a small present with the emblem of WiN Hungary. This form of communication has tested many times in our activity. It works very effectively. The form of poster is a chart flow of the process illustrated with photos. (author)

  16. 'Win-Win' or 'Win-Lose'?

    African Journals Online (AJOL)

    many years of exploitation, economic injustice and underdevelopment, many ... there is equality and absence of the exploitation or dominance motive. The ...... Labour Exploitation. China's economic operations in Africa have come into conflict with the labour movement on the continent on many frontiers. These range from.

  17. Fully Automated Quantification of the Striatal Uptake Ratio of [99mTc]-TRODAT with SPECT Imaging: Evaluation of the Diagnostic Performance in Parkinson’s Disease and the Temporal Regression of Striatal Tracer Uptake

    Directory of Open Access Journals (Sweden)

    Yu-Hua Dean Fang

    2015-01-01

    Full Text Available Purpose. We aimed at improving the existing methods for the fully automatic quantification of striatal uptake of [Tc99m]-TRODAT with SPECT imaging. Procedures. A normal [Tc99m]-TRODAT template was first formed based on 28 healthy controls. Images from PD patients (n=365 and nPD subjects (28 healthy controls and 33 essential tremor patients were spatially normalized to the normal template. We performed an inverse transform on the predefined striatal and reference volumes of interest (VOIs and applied the transformed VOIs to the original image data to calculate the striatal-to-reference ratio (SRR. The diagnostic performance of the SRR was determined through receiver operating characteristic (ROC analysis. Results. The SRR measured with our new and automatic method demonstrated excellent diagnostic performance with 92% sensitivity, 90% specificity, 92% accuracy, and an area under the curve (AUC of 0.94. For the evaluation of the mean SRR and the clinical duration, a quadratic function fit the data with R2=0.84. Conclusions. We developed and validated a fully automatic method for the quantification of the SRR in a large study sample. This method has an excellent diagnostic performance and exhibits a strong correlation between the mean SRR and the clinical duration in PD patients.

  18. Striatal and Extrastriatal Dopamine Transporter Availability in Schizophrenia and Its Clinical Correlates: A Voxel-Based and High-Resolution PET Study.

    Science.gov (United States)

    Artiges, Eric; Leroy, Claire; Dubol, Manon; Prat, Marie; Pepin, Audrey; Mabondo, Audrey; de Beaurepaire, Renaud; Beaufils, Béatrice; Korwin, Jean-Pierre; Galinowski, André; D'Albis, Marc-Antoine; Santiago-Ribeiro, Maria-João; Granger, Bernard; Tzavara, Eleni T; Martinot, Jean-Luc; Trichard, Christian

    2017-09-01

    Neuroimaging studies investigating dopamine (DA) function widely support the hypothesis of presynaptic striatal DA hyperactivity in schizophrenia. However, published data on the striatal DA transporter (DAT) appear less consistent with this hypothesis, probably partly due to methodological limitations. Moreover, DAT in extrastriatal regions has been very poorly investigated in the context of schizophrenia. In order to address these issues, we used a high resolution positron emission tomograph and the selective DAT radioligand [11C]PE2I, coupled with a whole brain voxel-based analysis method to investigate DAT availability in striatal but also extra-striatal regions in 21 male chronic schizophrenia patients compared to 30 healthy male controls matched by age. We found higher DAT availability in schizophrenia patients in midbrain, striatal, and limbic regions. DAT availability in amygdala/hippocampus and putamen/pallidum was positively correlated with hallucinations and suspiciousness/persecution, respectively. These results are consistent with an increase of presynaptic DA function in patients with schizophrenia, and support the involvement of both striatal and extrastriatal DA dysfunction in positive psychotic symptoms. The study also highlights the whole brain voxel-based analysis method to explore DA dysfunction in schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Emotional Intelligence and Will to Win: The Invincible and Invisible Phenomenon in Basketball Sports

    OpenAIRE

    SINGH, Davinder

    2015-01-01

    This study examined the emotional intelligence and will to win level among female basketball players. A group of fifty (N=50) female inter-college level basketball players of Guru Nanak Dev University, Amritsar, Punjab were selected for this study. The purposive sampling technique was used to attain the objectives of the study. All the subjects, after having been informed about the objective and protocol of the study, gave their consent and volunteered to participate in this st...

  20. Winning strategies of political campaigns in hybrid electoral spaces. Case study – Iasi County

    Directory of Open Access Journals (Sweden)

    Adrian Marius Tompea

    2012-10-01

    Full Text Available Our material introduces the concept of hybrid electoral area, as a distinct electoral entity set up by special territorial and administrative processes. We analyze specific cases of such spaces in Iasi and we see how the winning electoral strategies have been configured here. We provide examples of campaign activities and actions which ensured the candidates’ success by simultaneously targeting both the electoral sub-spaces and the community seen as whole.

  1. Inhibition of [3H]dopamine uptake into rat striatal slices by quaternary N-methylated nicotine metabolites

    International Nuclear Information System (INIS)

    Dwoskin, L.P.; Leibee, L.L.; Jewell, A.L.; Fang, Zhaoxia; Crooks, P.A.

    1992-01-01

    The effects of quaternary N-methylated nicotine derivatives were examined on in vitro uptake of [ 3 H]dopamine ([ 3 H]DA) in rat striatal slices. Striatal slices were incubated with a 10 μM concentration of the following compounds: N-methylnicotinium, N-methylnornicotinium, N-methylcotininium, N,N'-dimethylnicotinium and N'-methylnicotinium salts. The results clearly indicated that significant inhibition of [ 3 H]DA uptake occurred with those compounds possessing a N-methylpyridinium group; whereas, compounds that were methylated at the N'-pyrrolidinium position were less effective or exhibited no inhibition of [ 3 H]DA uptake. The results suggest that high concentrations of quaternary N-methylated nicotine metabolites which are structurally related to the neurotoxin MPP + , and which may be formed in the CNS, may protect against Parkinson's Disease and explain the inverse relationship between smoking and Parkinsonism reported in epidemiologic studies

  2. Transmission et plasticité activité-dépendante au niveau des synapses cortico-striatales

    OpenAIRE

    Fino, Elodie

    2007-01-01

    Le striatum a pour rôle de sélectionner et d'intégrer les informations provenant du cortex et ainsi construire et transmettre une réponse adaptée aux stimuli environnementaux. Nous avons caractérisé les propriétés électrophysiologiques des différents neurones du striatum (neurones de sortie, NETM, et interneurones) dans des conditions normales, et lors d'une déplétion de dopamine striatale. Grâce à un modèle de tranche de cerveau de rat dans laquelle les afférences cortico-striatales sont con...

  3. Selective Increase of Auditory Cortico-Striatal Coherence during Auditory-Cued Go/NoGo Discrimination Learning

    Science.gov (United States)

    Schulz, Andreas L.; Woldeit, Marie L.; Gonçalves, Ana I.; Saldeitis, Katja; Ohl, Frank W.

    2016-01-01

    Goal directed behavior and associated learning processes are tightly linked to neuronal activity in the ventral striatum. Mechanisms that integrate task relevant sensory information into striatal processing during decision making and learning are implicitly assumed in current reinforcement models, yet they are still weakly understood. To identify the functional activation of cortico-striatal subpopulations of connections during auditory discrimination learning, we trained Mongolian gerbils in a two-way active avoidance task in a shuttlebox to discriminate between falling and rising frequency modulated tones with identical spectral properties. We assessed functional coupling by analyzing the field-field coherence between the auditory cortex and the ventral striatum of animals performing the task. During the course of training, we observed a selective increase of functional coupling during Go-stimulus presentations. These results suggest that the auditory cortex functionally interacts with the ventral striatum during auditory learning and that the strengthening of these functional connections is selectively goal-directed. PMID:26793085

  4. Selective increase of auditory cortico-striatal coherence during auditory-cued Go/NoGo discrimination learning.

    Directory of Open Access Journals (Sweden)

    Andreas L. Schulz

    2016-01-01

    Full Text Available Goal directed behavior and associated learning processes are tightly linked to neuronal activity in the ventral striatum. Mechanisms that integrate task relevant sensory information into striatal processing during decision making and learning are implicitly assumed in current reinforcementmodels, yet they are still weakly understood. To identify the functional activation of cortico-striatal subpopulations of connections during auditory discrimination learning, we trained Mongolian gerbils in a two-way active avoidance task in a shuttlebox to discriminate between falling and rising frequency modulated tones with identical spectral properties. We assessed functional coupling by analyzing the field-field coherence between the auditory cortex and the ventral striatum of animals performing the task. During the course of training, we observed a selective increase of functionalcoupling during Go-stimulus presentations. These results suggest that the auditory cortex functionally interacts with the ventral striatum during auditory learning and that the strengthening of these functional connections is selectively goal-directed.

  5. Differential behavioral outcomes following neonatal versus fetal human retinal pigment epithelial cell striatal implants in parkinsonian rats

    DEFF Research Database (Denmark)

    Russ, Kaspar; Flores, Joseph; Brudek, Tomasz

    2017-01-01

    Following the failure of a Phase II clinical study evaluating human retinal pigment epithelial (hRPE) cell implants as a potential treatment option for Parkinson's disease, speculation has centered on implant function and survival as possible contributors to the therapeutic outcomes. We recently...... reported that neonatal hRPE cells, similar to hRPE cells used in the Phase II clinical study, produced short-lived in vitro and limited in vivo trophic factors, which supports that assumption. We hypothesize that the switch from fetal to neonatal hRPE cells, between the Phase I and the Phase II clinical...... following unilateral striatal implantation in 6-hydroxydopamine-lesioned rats. The results showed that only fetal, not neonatal, hRPE cell implants, were able to improve behavioral outcomes following striatal implantation in the lesioned rats. These data suggest that fetal hRPE cells may be preferential...

  6. Investing In The Army Organic Industrial Base To Operate And Win In A Complex And Austere Environment

    Science.gov (United States)

    2016-05-26

    background of the industrial base beginning with the period before the American Revolution and concluding with World War II when the American industrial ...Investing in the Army Organic Industrial Base to Operate and Win in a Complex and...05-2016 Monograph nJN 2015 - MAY 2016 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Investing in the Army Organic Industrial Base to Operate and Win in a

  7. Enabling Others to Win in a Complex World: Maximizing Security Force Assistance Potential in the Regionally Aligned Brigade Combat Team

    Science.gov (United States)

    2015-12-01

    security policy formulation. iii v Strategic Studies Institute and U.S. Army War College Press ENABLING OTHERS TO WIN IN A COMPLEX WORLD: MAXIMIZING...while also getting the best soldiers suited for advisor duty into those roles. 1 ENABLING OTHERS TO WIN IN A COMPLEX WORLD: MAXIMIZING SECURITY...of Defense Robert Gates noted: “strategic reality de- mands that the U.S. government get better at what is called ‘building partner capacity.’”1

  8. Promoting healthy weight: lessons learned from WIN the Rockies and other key studies.

    Science.gov (United States)

    Liebman, Michael

    2005-01-01

    In contrast to the traditional weight-centered approach, the Health At Every Size (HAES) or nondieting approach is health centered, with no focus on losing a predetermined amount of weight or fat. A key HAES principle of advocating healthy changes in food selection rather than adherence to prescriptive diets that involve calorie counting was adopted by Wellness in the Rockies (WIN the Rockies), a community-based research, intervention, and outreach project that promoted healthy lifestyles related to food, physical activity, and body image at the individual and community levels in Wyoming, Montana, and Idaho. The results from the project's cross-sectional surveys indicated that increased frequency of eating food while doing another activity, of drinking sweetened beverages such as soft drinks, and of consuming foods from fast-food restaurants were significant predictors of a high body mass index (BMI). In terms of energy expenditure, other predictors of high BMI from the WIN the Rockies cross-sectional surveys were lower frequency of participation in physical activity and the perception of not getting as much exercise as needed. The overall data provide support for the view that small diet- and physical activity-related lifestyle changes can cumulatively make a significant contribution to maintenance of healthy body weights. Although the community intervention emphasis of WIN the Rockies did not allow a specific assessment of the efficacy of HAES for individual participants in the project, this approach appears to hold great potential for promoting healthful lifestyle changes that improve quality of life.

  9. Winning and losing tree species of reassembly in Minnesota's mixed and broadleaf forests.

    Directory of Open Access Journals (Sweden)

    Brice B Hanberry

    Full Text Available We examined reassembly of winning and losing tree species, species traits including shade and fire tolerance, and associated disturbance filters and forest ecosystem types due to rapid forest change in the Great Lakes region since 1850. We identified winning and losing species by changes in composition, distribution, and site factors between historical and current surveys in Minnesota's mixed and broadleaf forests. In the Laurentian Mixed Forest, shade-intolerant aspen replaced shade-intolerant tamarack as the most dominant tree species. Fire-tolerant white pine and jack pine decreased, whereas shade-tolerant ashes, maples, and white cedar increased. In the Eastern Broadleaf Forest, fire-tolerant white oaks and red oaks decreased, while shade-tolerant ashes, American basswood, and maples increased. Tamarack, pines, and oaks have become restricted to sites with either wetter or sandier and drier soils due to increases in aspen and shade-tolerant, fire-sensitive species on mesic sites. The proportion of shade-tolerant species increased in both regions, but selective harvest reduced the applicability of functional groups alone to specify winners and losers. Harvest and existing forestry practices supported aspen dominance in mixed forests, although without aspen forestry and with fire suppression, mixed forests will transition to a greater composition of shade-tolerant species, converging to forests similar to broadleaf forests. A functional group framework provided a perspective of winning and losing species and traits, selective filters, and forest ecosystems that can be generalized to other regions, regardless of species identity.

  10. Winning and Losing Tree Species of Reassembly in Minnesota’s Mixed and Broadleaf Forests

    Science.gov (United States)

    Hanberry, Brice B.; Palik, Brian J.; He, Hong S.

    2013-01-01

    We examined reassembly of winning and losing tree species, species traits including shade and fire tolerance, and associated disturbance filters and forest ecosystem types due to rapid forest change in the Great Lakes region since 1850. We identified winning and losing species by changes in composition, distribution, and site factors between historical and current surveys in Minnesota’s mixed and broadleaf forests. In the Laurentian Mixed Forest, shade-intolerant aspen replaced shade-intolerant tamarack as the most dominant tree species. Fire-tolerant white pine and jack pine decreased, whereas shade-tolerant ashes, maples, and white cedar increased. In the Eastern Broadleaf Forest, fire-tolerant white oaks and red oaks decreased, while shade-tolerant ashes, American basswood, and maples increased. Tamarack, pines, and oaks have become restricted to sites with either wetter or sandier and drier soils due to increases in aspen and shade-tolerant, fire-sensitive species on mesic sites. The proportion of shade-tolerant species increased in both regions, but selective harvest reduced the applicability of functional groups alone to specify winners and losers. Harvest and existing forestry practices supported aspen dominance in mixed forests, although without aspen forestry and with fire suppression, mixed forests will transition to a greater composition of shade-tolerant species, converging to forests similar to broadleaf forests. A functional group framework provided a perspective of winning and losing species and traits, selective filters, and forest ecosystems that can be generalized to other regions, regardless of species identity. PMID:23613911

  11. Winning and losing tree species of reassembly in Minnesota's mixed and broadleaf forests.

    Science.gov (United States)

    Hanberry, Brice B; Palik, Brian J; He, Hong S

    2013-01-01

    We examined reassembly of winning and losing tree species, species traits including shade and fire tolerance, and associated disturbance filters and forest ecosystem types due to rapid forest change in the Great Lakes region since 1850. We identified winning and losing species by changes in composition, distribution, and site factors between historical and current surveys in Minnesota's mixed and broadleaf forests. In the Laurentian Mixed Forest, shade-intolerant aspen replaced shade-intolerant tamarack as the most dominant tree species. Fire-tolerant white pine and jack pine decreased, whereas shade-tolerant ashes, maples, and white cedar increased. In the Eastern Broadleaf Forest, fire-tolerant white oaks and red oaks decreased, while shade-tolerant ashes, American basswood, and maples increased. Tamarack, pines, and oaks have become restricted to sites with either wetter or sandier and drier soils due to increases in aspen and shade-tolerant, fire-sensitive species on mesic sites. The proportion of shade-tolerant species increased in both regions, but selective harvest reduced the applicability of functional groups alone to specify winners and losers. Harvest and existing forestry practices supported aspen dominance in mixed forests, although without aspen forestry and with fire suppression, mixed forests will transition to a greater composition of shade-tolerant species, converging to forests similar to broadleaf forests. A functional group framework provided a perspective of winning and losing species and traits, selective filters, and forest ecosystems that can be generalized to other regions, regardless of species identity.

  12. Win-stay-lose-learn promotes cooperation in the spatial prisoner's dilemma game.

    Directory of Open Access Journals (Sweden)

    Yongkui Liu

    Full Text Available Holding on to one's strategy is natural and common if the later warrants success and satisfaction. This goes against widespread simulation practices of evolutionary games, where players frequently consider changing their strategy even though their payoffs may be marginally different than those of the other players. Inspired by this observation, we introduce an aspiration-based win-stay-lose-learn strategy updating rule into the spatial prisoner's dilemma game. The rule is simple and intuitive, foreseeing strategy changes only by dissatisfied players, who then attempt to adopt the strategy of one of their nearest neighbors, while the strategies of satisfied players are not subject to change. We find that the proposed win-stay-lose-learn rule promotes the evolution of cooperation, and it does so very robustly and independently of the initial conditions. In fact, we show that even a minute initial fraction of cooperators may be sufficient to eventually secure a highly cooperative final state. In addition to extensive simulation results that support our conclusions, we also present results obtained by means of the pair approximation of the studied game. Our findings continue the success story of related win-stay strategy updating rules, and by doing so reveal new ways of resolving the prisoner's dilemma.

  13. Doubling Your Payoff: Winning Pain Relief Engages Endogenous Pain Inhibition1,2,3

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    Kwan, Saskia; Schweinhardt, Petra

    2015-01-01

    Abstract When in pain, pain relief is much sought after, particularly for individuals with chronic pain. In analogy to augmentation of the hedonic experience (“liking”) of a reward by the motivation to obtain a reward (“wanting”), the seeking of pain relief in a motivated state might increase the experience of pain relief when obtained. We tested this hypothesis in a psychophysical experiment in healthy human subjects, by assessing potential pain-inhibitory effects of pain relief “won” in a wheel of fortune game compared with pain relief without winning, exploiting the fact that the mere chance of winning induces a motivated state. The results show pain-inhibitory effects of pain relief obtained by winning in behaviorally assessed pain perception and ratings of pain intensity. Further, the higher participants scored on the personality trait novelty seeking, the more pain inhibition was induced. These results provide evidence that pain relief, when obtained in a motivated state, engages endogenous pain-inhibitory systems beyond the pain reduction that underlies the relief in the first place. Consequently, such pain relief might be used to improve behavioral pain therapy, inducing a positive, perhaps self-amplifying feedback loop of reduced pain and improved functionality. PMID:26464995

  14. RSAC 6.2 with WinRP 2.0 User Manual

    Energy Technology Data Exchange (ETDEWEB)

    Bradley Schrader

    2005-09-01

    The Radiological Safety Analysis Computer Program (RSAC-6.2) calculates the consequences of a release of radionuclides to the atmosphere. Using a personal computer, a user can generate a fission product inventory from either reactor operating history or a nuclear criticality accident. RSAC-6.2 models the effects of high-efficiency particulate air filters or other cleanup systems and calculates decay and ingrowth during transport through processes, facilities, and the environment. Doses are calculated for resuspension, inhalation, immersion, ground surface, and ingestion pathways. WinRP 2.0, a windows based overlay to RSAC-6.2, assists users in creating and running RSAC-6.2 input files. This users manual contains the mathematical models and operating instructions for RSAC-6.2 and WinRP 2.0. Instructions, screens, and examples are provided to guide the user through the functions provided by RSAC-6.2 and WinRP 2.0. These programs are designed for users who are familiar with radiological dose assessment methods.

  15. Highlights from the 2013 WIN Symposium: personalised cancer therapy from innovation to implementation.

    Science.gov (United States)

    Schilsky, Richard L

    2013-01-01

    The Worldwide Innovative Networking (WIN) consortium is a global alliance of academic and industrial cancer researchers, clinicians, and cancer advocacy groups set up to promote innovations in personalised cancer therapy and to accelerate the translation of research in this discipline into the oncology clinic. One of its most important initiatives is the WIN symposia, which have been held in Paris each summer since 2009. The fifth WIN symposium, which was held 10-12 July 2013, took as its overall theme 'Personalised Cancer Therapy: From Innovation to Implementation'. Over 400 delegates, including a good number of representatives of patient groups as well as leading academic, industrial, and clinical scientists; students; and post-docs attended this symposium. Its scientific programme featured thirty presentations divided into four main plenary sessions, and there was also a wide-ranging poster session that encompassed all the topics covered in the plenaries. The programme structure followed the path of drug discovery, in that the first session covered assay development for personalised cancer medicine; the second, applications of genomics in oncology; the third, clinical development; and the fourth, the impact of personalised medicine on cancer care.

  16. Striatal Dopamine D2/D3 Receptor Availability Is Associated with Executive Function in Healthy Controls but Not Methamphetamine Users.

    Directory of Open Access Journals (Sweden)

    Michael E Ballard

    Full Text Available Dopamine D2/D3 receptor availability in the striatum has been linked with executive function in healthy individuals, and is below control levels among drug addicts, possibly contributing to diminished executive function in the latter group. This study tested for an association of striatal D2/D3 receptor availability with a measure of executive function among research participants who met DSM-IV criteria for methamphetamine dependence.Methamphetamine users and non-user controls (n = 18 per group completed the Wisconsin Card Sorting Test and positron emission tomography with [18F]fallypride.The methamphetamine users displayed significantly lower striatal D2/D3 receptor availability on average than controls after controlling for age and education (p = 0.008, but they did not register greater proportions of either perseverative or non-perseverative errors when controlling for education (both ps ≥ 0.622. The proportion of non-perseverative, but not perseverative, errors was negatively correlated with striatal D2/D3 receptor availability among controls (r = -0.588, p = 0.010, but not methamphetamine users (r = 0.281, p = 0.258, and the group-wise interaction was significant (p = 0.030.These results suggest that cognitive flexibility, as measured by perseverative errors on the Wisconsin Card Sorting Test, is not determined by signaling through striatal D2/D3 receptors in healthy controls, and that in stimulant abusers, who have lower D2/D3 receptor availability, compensation can effectively maintain other executive functions, which are associated with D2/D3 receptor signaling in controls.

  17. Comparison of nitrogen narcosis and helium pressure effects on striatal amino acids: a microdialysis study in rats.

    Science.gov (United States)

    Vallée, Nicolas; Rostain, Jean-Claude; Boussuges, Alain; Risso, Jean-Jacques

    2009-05-01

    Exposure to nitrogen-oxygen mixture at high pressure induces narcosis, which can be considered as a first step toward general anaesthesia. Narcotic potencies of inert gases are attributed to their lipid solubility. Nitrogen narcosis induces cognitive and motor disturbances that occur from 0.3 MPa in man and from 1 MPa in rats. Neurochemical studies performed in rats up to 3 MPa have shown that nitrogen pressure decreases striatal dopamine release like argon, another inert gas, or nitrous oxide, an anaesthetic gas. Striatal dopamine release is under glutamatergic and other amino acid neurotransmission regulations. The aim of this work was to study the effects of nitrogen at 3 MPa on striatal amino acid levels and to compare to those of 3 MPa of helium which is not narcotic at this pressure, by using a new technique of microdialysis samples extraction under hyperbaric conditions, in freely moving rats. Amino acids were analysed by HPLC coupled to fluorimetric detection in order to appreciate glutamate, aspartate, glutamine and asparagine levels. Nitrogen-oxygen mixture exposure at 3 MPa decreased glutamate, glutamine and asparagine concentrations. In contrast, with helium-oxygen mixture, glutamate and aspartate levels were increased during the compression phase but not during the stay at maximal pressure. Comparison between nitrogen and helium highlighted the narcotic effects of nitrogen at pressure. As a matter of fact, nitrogen induces a reduction in glutamate and in other amino acids that could partly explain the decrease in striatal dopamine level as well as the motor and cognitive disturbances reported in nitrogen narcosis.

  18. Striatal and extrastriatal dopamine D2 receptor occupancy by a novel antipsychotic, blonanserin: a PET study with [11C]raclopride and [11C]FLB 457 in schizophrenia.

    Science.gov (United States)

    Tateno, Amane; Arakawa, Ryosuke; Okumura, Masaki; Fukuta, Hajime; Honjo, Kazuyoshi; Ishihara, Keiichi; Nakamura, Hiroshi; Kumita, Shin-ichiro; Okubo, Yoshiro

    2013-04-01

    Blonanserin is a novel antipsychotic with high affinities for dopamine D(2) and 5-HT(2A) receptors, and it was recently approved for the treatment of schizophrenia in Japan and Korea. Although double-blind clinical trials have demonstrated that blonanserin has equal efficacy to risperidone, and with a better profile especially with respect to prolactin elevation, its profile of in vivo receptor binding has not been investigated in patients with schizophrenia. Using positron emission tomography (PET), we measured striatal and extrastriatal dopamine D(2) receptor occupancy by blonanserin in 15 patients with schizophrenia treated with fixed doses of blonanserin (ie, 8, 16, and 24 mg/d) for at least 4 weeks before PET scans, and in 15 healthy volunteers. Two PET scans, 1 with [(11)C]raclopride for the striatum and 1 with [(11)C]FLB 457 for the temporal cortex and pituitary, were performed on the same day. Striatal dopamine D(2) receptor occupancy by blonanserin was 60.8% (3.0%) [mean (SD)] at 8 mg, 73.4% (4.9%) at 16 mg, and 79.7% (2.3%) at 24 mg. The brain/plasma concentration ratio calculated from D(2) receptor occupancy in the temporal cortex and pituitary was 3.38, indicating good blood-brain barrier permeability. This was the first study to show clinical daily dose amounts of blonanserin occupying dopamine D(2) receptors in patients with schizophrenia. The clinical implications obtained in this study were the optimal therapeutic dose range of 12.9 to 22.1 mg/d of blonanserin required for 70% to 80% dopamine D(2) receptor occupancy in the striatum, and the good blood-brain barrier permeability that suggested a relatively lower risk of hyperprolactinemia.

  19. Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons.

    Science.gov (United States)

    Martos, Yanina V; Braz, Barbara Y; Beccaria, Juan P; Murer, M Gustavo; Belforte, Juan E

    2017-03-15

    The mechanisms underlying social dysfunction in neuropsychiatric conditions such as obsessive-compulsive disorder and Tourette syndrome remain uncertain. However, it is known that dysfunctions in basal ganglia, including a reduced number of striatal cholinergic interneurons (SCIN), are involved in their pathophysiology. To explore the role of SCIN in relation to perseverative behaviors, we characterized a new transgenic mouse model in which inducible ablation of SCIN is achieved with high efficiency in a cell-type- and region-specific manner. Mice were subjected to extensive behavioral testing, including assessment of social behaviors, and corticostriatal functional connectivity was evaluated in vivo Selective SCIN ablation leads to altered social interactions together with exacerbated spontaneously emitted repetitive behaviors. Lesioned mice showed normal motor coordination, balance, and general locomotion. Interestingly, only environmentally driven, but not self-directed, repetitive behaviors were exacerbated in lesioned mice. Remarkably, in mice with SCIN ablation, the normal pattern of social exploration was replayed continuously. The emerging pattern of social interactions is highly predictable and invariant across time. In vivo electrophysiological recordings indicate that SCIN ablation results in an increase of the functional connectivity between different cortical areas and the motor, but not associative, region of the striatum. Our results identify a role of SCIN in suppressing perseverative behaviors, including socially related ones. In sum, SCIN ablation in mice leads to exacerbated ritualistic-like behaviors that affect social performance, providing a link between SCIN dysfunction and the social impairments present in psychiatric disorders. SIGNIFICANCE STATEMENT We sought to uncover the impact of striatal cholinergic interneuron (SCIN) degeneration on perseverative behaviors related to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). We

  20. Revisiting the 'self-medication' hypothesis in light of the new data linking low striatal dopamine to comorbid addictive behavior.

    Science.gov (United States)

    Awad, A George; Voruganti, Lakshmi L N P

    2015-06-01

    Persons with schizophrenia are at a high risk, almost 4.6 times more likely, of having drug abuse problems than persons without psychiatric illness. Among the influential proposals to explain such a high comorbidity rate, the 'self-medication hypothesis' proposed that persons with schizophrenia take to drugs in an effort to cope with the illness and medication side effects. In support of the self-medication hypothesis, data from our earlier clinical study confirmed the strong association between neuroleptic dysphoria and negative subjective responses and comorbid drug abuse. Though dopamine has been consistently suspected as one of the major culprits for the development of neuroleptic dysphoria, it is only recently our neuroimaging studies correlated the emergence of neuroleptic dysphoria to the low level of striatal dopamine functioning. Similarly, more evidence has recently emerged linking low striatal dopamine with the development of vulnerability for drug addictive states in schizophrenia. The convergence of evidence from both the dysphoria and comorbidity research, implicating the role of low striatal dopamine in both conditions, has led us to propose that the person with schizophrenia who develops dysphoria and comorbid addictive disorder is likely to be one and the same.