Дисертації з теми "Natural rewards"

Repeated exposure to psychostimulant drugs induces numerous behavioral, and neuronal changes, which in animals is thought to model certain neural adaptations that may contribute to drug addiction. Chronic AMPH has repeatedly been shown to alter the acquisition and expression of associations between a conditioned stimulus (CS) and natural rewards. Although repeated psychostimulant exposure can interfere with associative learning about natural food rewards, the manner in which these treatments affect acquisition and expression of these associations remains unclear. The current study investigated how repeated AMPH exposure (5 x 2 mg/kg over 10 days) affects learning, extinction and cue-induced reinstatement of instrumental responding of food-seeking behavior. Rats were trained over 7 days to press one of two levers for food and a tone/light CS. During subsequent extinction conducted over 3-6 days, responding delivered neither food nor the CS. On reinstatement tests, active lever presses produced the CS, but not food. Rats received repeated AMPH or saline prior to training (exp. 1A), after instrumental training (exp. 1B), or after training and extinction (exp. 1C). In experiment 1A, cue-induced reinstatement was blunted significantly in AMPH-treated rats. In contrast, AMPH-treatment after initial training (experiment 1B) significantly retarded extinction relative to controls, but did not affect cue-induced reinstatement. In experiment 1C, AMPH exposed rats displayed enhanced cue-induced reinstatement. Experiment 2 was conducted to clarify the results of experiment 1A. Rats were trained to nosepoke for food following a CS, and were then tested in the presence of two novel levers, responding on one delivered the food-associated CS. AMPH treatment impaired the acquisition of a new response with conditioned reinforcement. These findings suggest that repeated AMPH exposure prior to formation of response-CS associations selectively disrupts the ability of food-related stimuli to influence instrumental responding. Exposure after initial associative learning impedes extinction. AMPH administration after training and extinction enhance responding. Collectively, these findings suggest that AMPH sensitization can perturb certain aspects of amygdala-mediated associative learning related to natural, food rewards, and this impairment seems to reflect a weakened CS-reward association as opposed to a reduced preference for the food.

Little research has been done on antonymic relations, a great deal of this has been done by linguists Paradis et al. Gamification was used in natural language acquisition by Bos and Nissim in their 2015 study about noun-noun compound relations, but gamification of information retrieval remains a relatively new field of study. This thesis reproduced work done by Paradis et al. in an attempt to answer the following questions for Swedish antonyms: will reversing word order in antonymic relations affect the strength of said word pair? Will the perceived strength of canonical antonyms have a lower variance than that of non-canonical antonyms? It will also examine whether giving points depending on the agreement with other users reduce the occurrence of extreme points on an ordinal scale? Two parallel studies were conducted, one using a web app which implemented consensus driven rewards, and another utilising a questionnaire. Reversing the order of the words did not to alter the perceived strength of the antonymic pair, which is consistent with the results acquired by Paradis et al. in 2009. Results regarding variance of canonical and non-canonical antonym pairs were inconclusive. An implementation with consensus driven rewards yielded more extreme values than the questionnaire. More research is suggested to improve the strength of the results.
Lite forskning har gjorts om antonymer inom natural language acquisition, och mycket av den forskning som finns om antonymer är gjord av Paradis et al. inom lingvistik. Gamifiering har använts inom natural language acquisition, bland annat av Bos och Nissim i deras studie om relationer hos sammansatta substantiv från 2015. Denna rapport försöker besvara följande frågor om svenska antonymer: spelar ordningen på ord i ett antonympar någon roll i hur parets antonymiska styrka uppfattas? Kommer den uppfattade styrkan hos kanoniska antonympar ha lägre varians än deras ickekanoniska motsvarigheter? Rapporten undersöker även huruvida konsensusdriven poängsättning påverkar förekomsten av extremvärden på en ordinalskala. Två parallella delstudier utfördes, en webapp som implementerade konsensusdriven poängsättning, samt ett frågeformulär utan poängsättning. Ordningen av orden i ett antonympar hade ingen signifikant påverkan på dess uppfattade styrka, i enighet med Paradis et al.s studie från 2009. Resultaten angående kanoniska antonymers varians var inte entydiga. Implementationen med konsensusbaserad poängsättning gav fler extremvärden än frågeformuläret. Eftersom detta var en liten studie behövs vidare undersökning för att stärka resultaten.

In the last decade, (non)prescription opioid abuse, opioid use disorder (OUD) diagnoses, and opioid-related overdoses have risen and represent a significant public health concern. One method of understanding OUD is as a disorder of choice that requires choosing opioid rewards at the expense of other nondrug rewards. The characterization of OUD as a disorder of choice is important as it implicates decision- making processes as therapeutic targets, such as the valuation of opioid rewards. However, reward-value measurement and interpretation are traditionally different in substance abuse research compared to related fields such as economics, animal behavior, and neuroeconomics and may be less effective for understanding how opioid rewards are valued. The present research therefore used choice procedures in line with behavioral/neuroeconomic studies to determine if drug-associated decision making could be predicted from economic choice theories. In Experiment 1, rats completed an isomorphic food-food probabilistic choice task with dynamic, unpredictable changes in reward probability that required constant updating of reward values. After initial training, the reward magnitude of one choice subsequently increased from one to two to three pellets. Additionally, rats were split between the Signaled and Unsignaled groups to understand how cues modulate reward value. After each choice, the Unsignaled group received distinct choice-dependent cues that were uninformative of the choice outcome. The Signaled group also received uninformative cues on one option, but the alternative choice produced reward-predictive cues that informed the trial outcome as a win or loss. Choice data were analyzed at a molar level using matching equations and molecular level using reinforcement learning (RL) models to determine how probability, reward magnitude, and reward-associated cues affected choice. Experiment 2 used an allomorphic drug versus food procedure where the food reward for one option was replaced by a self-administered remifentanil (REMI) infusion at doses of 1, 3 and 10 μg/kg. Finally, Experiment 3 assessed the potential for both REMI and food reward value to be commonly scaled within the brain by examining changes in nucleus accumbens (NAc) Oxygen (O2) dynamics. Results showed that increasing reward probability, magnitude, and the presence of reward-associated cues all independently increased the propensity of choosing the associated choice alternative, including REMI drug choices. Additionally, both molar matching and molecular RL models successfully parameterized rats’ decision dynamics. O2 dynamics were generally commensurate with the idea of a common value signal for REMI and food with changes in O2 signaling scaling with the reward magnitude of REMI rewards. Finally, RL model-derived reward prediction errors significantly correlated with peak O2 activity for reward delivery, suggesting a possible neurological mechanism of value updating. Results are discussed in terms of their implications for current conceptualizations of substance use disorders including a potential need to change the discourse surrounding how substance use disorders are modeled experimentally. Overall, the present research provides evidence that a choice model of substance use disorders may be a viable alternative to the disease model and could facilitate future treatment options centered around economic principles.

Gli endocannabinoidi giocano un ruolo fondamentale nella regolazione della trasmissione sinaptica. L’esposizione ad eventi stressanti o gratificanti induce modificazioni sinaptiche nelle diverse aree cerebrali. L’attività del sistema degli endocannabinoidi nei circuiti neuronali coinvolti nelle risposte allo stress e alla gratificazione (reward) suggerisce il suo coinvolgimento nelle risposte comportamentali e negli adattamenti a livello sinaptico tipiche dello stress, delle droghe d’abuso ed altre forme di comportamenti reward dipendenti. In questo studio, mediante l’utilizzo di registrazioni elettrofisiologiche abbiamo dimostrato che lo stress indotto in topi cronicamente esposti ad aggressione (social defeat stress) e reward naturali come arricchimento ambientale e consumo di una soluzione contenente saccarosio (3%), alterano in modo opposto il controllo delle trasmissione sinaptica mediato dai recettori dei cannabinoidi CB1 nello striato. Lo striato svolge un ruolo centrale nelle funzioni motorie comportamentali ed emotive modulate dallo stress e da eventi gratificanti; in questa struttura i recettori CB1 sono espressi a livelli elevati modulando la trasmissione sinaptica sia inibitoria che eccitatoria. Nel corso di questo lavoro, abbiamo dimostrato che l’ inibizione presinaptica delle correnti GABAergiche inibitorie indotta dall’agonista dei recettori CB1 HU210, è abolita in topi esposti a stress cronico, mentre risulta significativamente potenziata a seguito di trattamenti gratificanti quali arricchimento ambientale e consumo di saccarosio. La sensibilità dei recettori CB1 espressi sui terminali glutammatergici risulta invece inalterata, così come quella dei recettori GABAB espressi presinapticamente sulle sinapsi GABAergiche, suggerendo che le alterazioni registrate in cellule di animali esposti ai protocolli di stress e reward, siano limitate ai recettori presinaptici CB1 GABAergici. Le alterazioni delle risposte CB1 mediate sono lentamente reversibili e sono riscontrabili anche a seguito della stimolazione dei recettori metabotropici del glutammato 5, responsabili della mobilizzazione dei cannabinoidi endogeni. Abbiamo inoltre osservato che l’aumento dell’ inibizione presinaptica delle correnti GABAergiche inibitorie CB1-mediata a seguito di trattamenti gratificanti quali arricchimento ambientale e consumo di saccarosio, svolge un ruolo cruciale di protezione dalle conseguenze sinaptiche e comportamentali indotte da stress. Infine, abbiamo esteso i nostri studi all’interazione tra i recettori CB1 e il BDNF, molecola coinvolta nelle conseguenze comportamentali delle esperienze di stress e di gratificazione. Il BDNF inibisce l’attività dei CB1 nello striato, attraverso un meccanismo tirosina chinasi dipendente e questa inibizione è riscontrabile anche a seguito della sensitizzazione reward-mediata di questi recettori. La regolazione BDNF mediata dei recettori CB1 potrebbe avere un ruolo rilevante nelle funzioni cognitive e comportamentali, mentre un’azione diretta sui recettori CB1 e sul metabolismo degli endocannabinoidi potrebbe essere valutato nel trattamento di disturbi neuropsichiatrici associati allo stress.
The endocannabinoid system plays a fundamental role in the regulation of synaptic transmission. Exposure to stressful or rewarding events triggers synaptic adaptations in many brain areas. The activity of the endocannabinoid system in stress-responsive neural circuits and central reward pathway suggests that it may be involved in the behavioural responses and synaptic effects typical of stress, drug addiction an other forms of reward-based behaviors. In the present study, by means of electrophysiological recordings we found that social defeat stress, induced in mice by exposure to aggression, and natural rewards such as running wheel and sucrose consumption, alter in opposite way the cannabinoid CB1 receptor-mediated control of synaptic transmission in the striatum. The striatum plays a central role in motor, cognitive and emotional functions modulated by stress and rewarding agents, and contains high levels of cannabinoid receptors controlling both excitatory and inhibitory synaptic transmission . We found that the presynaptic inhibition of GABAergic inhibitory postsynaptic currents induced by the cannabinoid CB1 receptor agonist HU210 was abolished after chronic stress exposure, whereas it was remarkably potentiated after running wheel and sucrose consumption. In contrast, the sensitivity of glutamate synapses to CB1 receptor stimulation was unaltered, as well as that of GABA synapses to the stimulation of other presynaptic receptors such as GABAB. The alterations of cannabinoid CB1 receptor-mediated responses were slowly reversible and were also detectable following the mobilization of endocannabinoids by metabotropic glutamate receptor 5 stimulation. Finally, we found that the up-regulation of cannabinoid transmission induced by wheel running or sucrose played a crucial role in the protective effects of these environmental manipulations against the motor and synaptic consequences of stress. Since BDNF also play a role in the emotional consequences of stress and of rewarding experiences, we have extended our study to address the functional interplay between BDNF and cannabinoid CB1 receptors in the striatum. We found that BDNF potently inhibits CB1 receptor function in the striatum. The action of BDNF on CB1 receptor function was tyrosine kinase dependent, and was complete even after receptor sensitization with behavioral manipulations activating the reward system. BDNF-mediated regulation of striatal CB1 receptors might have relevant roles in cognitive and behavioral functions and targeting cannabinoid CB1 receptors or endocannabinoid metabolism might be a valuable option to treat stress-associated neuropsychiatric conditions.

Le tabagisme, qui concerne un milliard de personnes à travers le monde, est à l’origine de plus de 8 millions de décès évitables par an, et constitue ainsi un enjeu sanitaire majeur. La nicotine, principal composé actif du tabac, agit au niveau du système nerveux en se liant aux récepteurs nicotiniques de l’acétylcholine (nAChR). Cette liaison produit de manière concomitante des effets récompensants et aversifs, permettant respectivement de promouvoir et limiter la consommation de tabac. Les nAChR sont exprimés au niveau du système de la récompense, notamment l’aire tegmentale ventrale (VTA), mais également dans de nombreuses autres régions cérébrales perturbées par la nicotine. L’objectif de mes travaux de thèse a été d’étudier l’effet de la nicotine sur deux voies cérébrales centrées sur la VTA et non canoniques : la voie reliant noyau interpédonculaire (IPN) et la VTA d’une part, et la voie projetant de la VTA vers le claustrum (CLA) d’autre part. J’ai dans un premier temps étudié l’implication de l’IPN dans le renforcement à la nicotine. Nous avons montré que les neurones de l’IPN répondent de manière hétérogène à la nicotine, et découvert qu’ils sont sensibles à de faibles doses de nicotine qui n’activent pas la VTA. A l’aide de nouveaux outils chémogénétiques que j’ai développés, nous avons mis en évidence que les nAChR contenant β4 de l’IPN jouent un rôle de frein sur la réponse à la nicotine dans la VTA, et diminuent ainsi l’effet récompensant de la drogue. L’IPN ne jouerait donc pas uniquement un rôle dans l’aversion mais également dans le renforcement à la nicotine. Dans un second temps, j’ai étudié comment une exposition prolongée à la nicotine modifie les interactions sociales, et comment la voie VTA-CLA pourrait participer à ces perturbations comportementales. Nous avons observé qu’une exposition chronique à la nicotine produit une augmentation de la saillance d’un stimulus social nouveau dans une tâche trois-chambres, se traduisant par une augmentation du temps passé avec le nouveau congénère. De plus, l’activation optogénétique de la voie VTA-CLA induit une perte de la préférence pour le stimulus social nouveau dans la tâche trois-chambre, tandis que la stimulation optogénétique non contingente reproduit les effets comportementaux d’une exposition prolongée à la nicotine. La voie VTA-CLA semble donc impliquée dans la saillance pour de nouveaux stimuli sociaux, et cette fonction serait perturbée par la nicotine chronique. L’ensemble de ces travaux permet de mettre en évidence l’importance de ces deux nouvelles voies non canoniques dans l’addiction à la nicotine
Smoking affects one billion people worldwide, and is responsible for over 8 million preventable deaths a year, making it a major health concern. Nicotine, the main active compound in tobacco, acts on the nervous system by binding to nicotinic acetylcholine receptors (nAChRs). There is a wide diversity of nAChR subunits (��2 to 10 and β2 to 4) which assemble in different combinations to form pentameric receptors with different biophysical properties and localizations. Nicotine concomitantly produces rewarding and aversive effects, promoting and limiting nicotine consumption, respectively. While nAChRs are expressed in the reward system, notably the ventral tegmental area (VTA), they are also present in many other brain regions susceptible to nicotine-induced disruptions. The aim of my thesis work was to investigate the involvement of two non-canonical VTA-connected brain pathways in nicotine addiction: the pathways linking the interpeduncular nucleus (IPN) and the VTA, and the one connecting the VTA to the claustrum (CLA). I first studied the involvement of the IPN in nicotine reinforcement. We showed that IPN neurons respond heterogeneously to nicotine, and discovered that they are sensitive to low doses of nicotine that do not activate the VTA. Using new chemogenetic tools that I have developed, we have shown that β4-containing nAChRs of the IPN act as a brake on the response to nicotine in the VTA, thereby reducing the rewarding effects of the drug. The IPN would therefore contribute not only to aversion but also to nicotine reinforcement. Secondly, I studied how prolonged exposure to nicotine alters social interactions, and the potential involvement of the VTA-CLA pathway in these behavioral perturbations. We showed that chronic nicotine exposure increased the saliency of a novel social stimulus in a three-chamber task, resulting in an increased interaction time with novel conspecifics. Moreover, optogenetic activation of the VTA-CLA pathway induced a loss of preference for the novel social stimulus, while non-contingent optogenetic stimulation replicated the behavioral effects of prolonged nicotine exposure. Therefore, the VTA-CLA pathway seems to be involved in the saliency for new social stimuli, and this function may be disrupted by chronic nicotine exposure. Taken together, these studies highlight the importance of these two non-canonical pathways in nicotine addiction

Thesis (Ph. D.)--University of Cincinnati, 2005.
Title from electronic thesis title page (viewed Mar. 23, 2006). Includes abstract. Keywords: limbic, reward, plasticity. Includes bibliographical references.

Nicotinic acetylcholine receptors (nAChR) are neurotransmitter-gated ion channels that exist as a family of subtypes defined by unique subunit compositions. nAChR containing α6 subunits (α6*-nAChR) have attracted interest because α6 subunits are thought to be localized in brain regions implicated in reward, mood and drug dependence. To provide new information necessary toward a more complete understanding of roles of α6*-nAChR in neuropsychiatric health and disease, three lines of investigation were pursued. A set of stably transfected, human, immortalized cell lines were generated that heterologously express nAChR α6 subunits in combination with other nAChR subunits found in reward brain regions (nAChR subunit combinations α6β2, α6β4, α6β2β3, α6β4β3, α6β2β3α5, α6β4β3α5, α6α4β2β3 and α6α4β4β3). The α6α4β2β3 combination may have a functional response to epibatidine that differs from that of the α4β2 nAChR. A unique binding site was identified in cells transfected with the α6β4β3α5 nAChR subunit combination. Messenger RNA fluorescence in situ hybridization (mRNA FISH) studies established regional and celluar distribution of nAChR α6 subunit mRNA in the mouse brain. The third line of study extended this work to examine potential co-expression of nAChR α6 subunits and glutamic acid decarboxylase (GAD) or tyrosine hydroxylase (TH) as labels of GABAergic and dopaminergic/catecholaminergic neurons respectively, using tandem mRNA FISH and fluorescence immunohistochemistry. nAChR α6 subunit signal in the substantia nigra (SN) and ventral tegmental area (VTA) was congruent with previous studies. Message was also detected in the amydala, dentate gyrus, striatum, zona incerta, and cingulate, entorhinal, perirhinal, piriform, and prelimbic cortices. nAChR α6 mRNA was coexpressed with GAD in the amygdala, dentate gyrus, striatum, SN, VTA and cingulate, entorhinal, prelimbic and prelimbic cortices. TH was exclusively co-localized with nAChR α6 mRNA in the SN and VTA. Findings suggest extended roles for α6*-nAChR in the brain, particularly in the control of GABAergic neuronal activity and/or GABA release. These studies provide new insights into the composition of α6*-nAChR, the localization and cellular origins of nAChR α6 subunit expression. Data collected suggest roles for α6*-nAChR in many brain regions, including those involved in higher order processes involved in drug dependence and reward, and in modulation of inhibitory neurotransmission.

Magister Commercii - MCom
Background: Many South African companies are faced with the challenge of integrating a racially-diverse workforce into a white-dominated environment. This research sets out to assess the relationship between race and engagement activities within the workplace. Significance/Objective of the Research: This study aims to explore employee engagement and how employees of different races perceive their work environment, and in so doing, enhance the employer's ability to respond. Research Methodology: The analysis made use of confirmatory and exploratory factor analysis and structural equation modelling to validate the employee engagement concepts of an empirical survey that was conducted across all trading divisions within the retail group. Ethics Statement: The research survey ensured ethics by assuring respondents voluntarily contributed to the research, whilst guaranteeing them anonymity, honesty and full disclosure. Findings/Conclusion: The study confirms that race, leadership, nature of job, intent to stay, empowerment, relationship and reward are factors influencing engagement amongst employees within the South African retail group.

In the field of neuroscience, being in love and feeling romantically attached to a partner is described as a dynamic process. Romantic love may be viewed as a motivational system, changing throughout time and place, fluctuating on the interest and motivation of the individual. Early memories and attachment towards a caregiver, lay the foundation for later attachment behavior, also known as attachment styles. In this thesis, an exploratory approach is present. The thesis aims to introduce and describe the neural correlates of romantic love and romantic attachment. Brain regions concerned with reward, emotion and thought processing, such as the reward circuitry network of the brain and the limbic system, are being investigated. So are other brain areas involved in romantic love and romantic attachment. Research findings suggest that brain areas responsible for affection, emotional control, learning, memory and social judgment are all involved in the complex processes of being in love and feeling romantically attached. These findings are represented by the involvement of the frontal lobe, cerebral cortex, limbic system, orbitofrontal cortex, and hippocampus, anterior cingulate cortex (ACC), ventral tegmental area (VTA), caudate tail, including the reward pathways of the brain. Distribution and regulation of neurotransmitters such as; vasopressin, oxytocin, dopamine, corticosterone and serotonin are all present in the state of romantic  attachment and romantic love. Overlapping evidence confirms the involvement of the reward circuitry network, together with the limbic system as crucial in the formation and maintenance of a romantic relationship.

La prise volontaire de nicotine augmente l'excitabilité de la voie ILCx-BNST, entraînant une hyperactivité des neurones DA de l’ATV. Dans une première partie, l'objectif était d’étudier les neuroadaptations de la voie ILCx-BNST induites par l'auto-administration intraveineuse (AAIV) de nicotine. Les récepteurs cannabinoides CB1 contrôlent les propriétés renforçantes de la nicotine. Par conséquent, nous avons examiné le rôle des récepteurs CB1 du BNST. Nous montrons que l'acquisition de l’AAIV de nicotine est associée à une facilitation persistante de l'induction d’une potentialisation à long terme (LTP) CB1-dépendantes des synapses ILCx-BNST. La stimulation électrique du ILCx favorise également la persistance du comportement de recherche de nicotine pendant les périodes où la drogue n'est pas disponible. En outre, en utilisant la pharmacologie intra-BNST, nous montrons que la stimulation des récepteurs CB1 du BNST au cours de l’acquisition de lAAIV augmente la sensibilité aux stimuli associés à la nicotine. L’idée qu’il existe un appétit incontrôlable pour les aliments palatables, en dépit des conséquences négatives. Dans une seconde partie, notre projet a porté sur le rôle des neurones dopaminergiques (DA) de l’ATV dans la perception d’un stimulus aversif chez l’animal exposé au sucrose. Nos résultats indiquent que le sucrose augmente l'activité spontanée des neurones DA de la VTA. En outre, si un choc électrique provoque une inhibition presque complète de l'activité de VTA neurones DA chez les rats témoins, le sucrose perturbe la signalisation d'un stimulus aversif, indépendamment de l’état calorique du rat
Learning mechanisms associated with active responding for nicotine enhanced the excitability of the ILCx-BNST pathway. The objective of this project was to better understand the involvement of the ILCx-BNST pathway in nicotine self-administration. Since the endocannabinoid system controls nicotine reinforcement and nicotine-induced synaptic modifications, we examined the role of CB1 receptors in the BNST. We showed that acquisition of nicotine IVSA was associated with a persistent facilitation of LTP induction at ILCx-BNST synapses. Behaviorally, electrical stimulation temporarily increased excessive responding to nicotine when nicotine was not available. Moreover, using intra-BNST pharmacology, we revealed that stimulation of BNST CB1 receptors enhanced sensitivity to nicotine-paired cue. In contrast, after a prolonged history of nicotine intake, it blocked drug-seeking in a reinstatement model of relapse. Drug addiction is partly due to the inability to stop using despite negative consequences. The hypothesis that palatable food induces similar uncontrolled consumption is becoming more widespread. As drug addiction is known to increases activity of VTA DA neurons, we aimed to examine whether exposure to sucrose would induce similar neuronal modifications and impair the capacity to respond to an aversive stimulus. We found that sucrose enhanced spontaneous activity of DA VTA neurons. In addition, while a footshock caused a nearly complete inhibition of activity of VTA DA neurons in control rats, sucrose disrupted signaling of an aversive stimulus. These modifications were independent from the caloric state of the rats

Research Doctorate - Doctor of Philosophy (PhD)
The lateral hypothalamus (LH) is anatomically positioned to receive and send an array of afferent and efferent signals within the brain. This is important as distinct behaviours relating to homeostasis are coordinated and executed by LH cells and signalling pathways. The LH can control appetitive behaviour as well as motivation and reward-seeking, as well as being sensitive to stress signals. Importantly, the LH has a heterogenous composition, comprising of many diverse cell types. The functional importance of these intra-LH populations is incompletely understood. Further, neuroscience research is only recently beginning to unravel the complex nature of afferent signals which can help control output from the LH. Afferent projections from brains areas such as the paraventricular nucleus of the hypothalamus (PVN) and nucleus accumbens shell (NAcSh) can control stress and reward-related behaviour, respectively. These regions are well positioned anatomically and physiologically to send important communications to the LH in order to help maintain homeostatic functioning. This thesis firstly demonstrated that early life stress-induced motivational deficits have the capacity to be overcome by chemogenetic manipulation of the LH. Next, we saw that repeated optogenetic stimulation of the PVN can reduce motivational drive for natural rewards. Importantly, these changes could be recapitulated by isolating the PVN→LH pathway. Lastly, using fibre photometry we found that orexin neurons almost exclusively respond to approach behaviour to food pellets and that the activity of orexin neurons depended on metabolic state and the palatability or caloric value of the food. Additionally, we provide electrophysiological evidence that this behaviour may be mediated by an inhibitory projection from the NAcSh. Overall, this work demonstrates that hypothalamic and extra-hypothalamic brain regions can provide vital input to the LH in mediating stress and motivated behaviours.

This thesis analyses the biggest reward-based crowdfunding platform in the Czech Repub- lic using textual tools on uniquely collected microdata. The research question investigates which of the attributes of project campaigns (including the language style of project de- scriptions) have a significant impact on successful funding. Empirical analysis combines results of Bayesian Model Averaging and logistic regression. Results reveal that firstly, language style of project descriptions does not possess any significant predictive power. Secondly, that utilization of a video, size of pledging goal, or the number of contributors have a significant effect on the campaign's success, which is in line with current literature. Thirdly, it has proven to be true that project categorization plays an important role as well. On the contrary, the findings do not imply any causal claims, such as whether those factors persuade contributors to donate money. JEL Classification G23 Keywords crowdfunding, rewards, success determinants, natural language processing Author's e-mail t.hudcova@gmail.com Supervisor's e-mail polakpet@gmail.com

The human visual system is remarkable for the variety of functions it can be used for and the range of conditions under which it can perform, from the detection of small brightness changes to guiding actions in complex movements. The human eye is foveated and humans continually make eye and body movements to acquire new visual information. The mechanisms that control this acquisition and the associated sequencing of eye movements in natural circumstances are not well understood. While the visual system has highly parallel inputs, the fovea must be moved in a serial fashion. A decision process continually occurs where peripheral information is evaluated and a subsequent fixation target is selected. Prior explanations for fixation selection have largely focused on computer vision algorithms that find image areas with high salience, ones that incorporate reduction of uncertainty or entropy of visual features, as well as heuristic models. However, these methods are not well suited to model natural circumstances where humans are mobile and eye movements are closely coordinated for gathering ongoing task information. Following a computational model of gaze scheduling proposed by Sprague and Ballard (2004), I argue that a systematic explanation of human gaze behavior in complex natural tasks needs to represent task goals, a reward structure for these goals and a representation of uncertainty concerning progress towards those goals. If these variables are represented it is possible to formulate a decision computation for choosing fixation targets based on an expected value from uncertainty weighted reward. I present two studies of human gaze behavior in a simulated driving task that provide evidence of the human visual system’s sensitivity to uncertainty and reward. In these experiments observers tended to more closely monitor an information source if it had a high level of uncertainty but only for information also associated with high reward. Given this behavioral finding, I then present a set of simple candidate models in an attempt to explain how humans schedule the acquisition of information over time. These simple models are shown to be inadequate in describing the process of coordinated information acquisition in driving. I present an extended version of the gaze scheduling model adapted to our particular driving task. This formulation allows ordinal predictions on how humans use reward and uncertainty in the control of eye movements and is generally consistent with observed human behavior. I conclude by reviewing main results and discussing the merits and benefits of the computational models used, possible future behavioral experiments that would serve to more directly test the gaze scheduling model, as well as revisions to future implementations of the model to more appropriately capture human gaze behavior.
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碩士
國立成功大學
行為醫學研究所
95
A large body of evidence supports the hypothesis that monoamines are involved in the cocaine craving and associated behavior. Cocaine has been known to block reuptake of these neurotransmitters by inhibiting their own transporters, thus enhance synaptic availability of these neurotransmitters. Increased synaptic monoamine concentration have been associated with the euphoric (reinforcing) efficacy and the priming effects of cocaine in reinstatement designs. In this study, the acquisition curve of cocaine self administration was examined in MAO subtype B knockout mice and long-term MAO inhibitor-treated mice. We found that 1) chronic MAO inhibitor (MAOI) treatment did not seem to affect the natural reward (food)-associated operant conditioning, while attenuated the rewarding effects of cocaine; 2) the responses for cocaine self administration in MAO subtype B knockout mice were higher than them in the wild type mice, however there was a similar acquisition curve for the food reward in knockout and wild type mice.

Trabalho de projeto de mestrado em Matemática Aplicada à Economia e Gestão, Universidade de Lisboa, Faculdade de Ciências, 2020
Os programas de fidelização apresentam neste momento um alcance global, consequência do aumento exponencial da globalização e da era digital. Paradoxalmente, as taxas de abandono destes programas são elevadas. A saturação do conceito tradicional de programas de fidelização pode ser uma das causas para os utilizadores usarem cada vez menos este tipo de programas. É assim necessário criar estratégias para conseguir atrair de novo o interesse do consumidor nos programas de fidelização. O objetivo deste trabalho passa por perceber se a criação de um programa multi-entidades beneficia todos os intervenientes. Este programa de fidelização, de forma a diferenciar-se dos atuais programas desta natureza não deve limitar o utilizador na forma como este decide usufruir das suas recompensas. Este programa também se distingue por simplificar a usabilidade do utilizador uma vez que agrega numa só plataforma várias entidades. Como forma de enquadramento da investigação, é estudada a evolução das necessidades do consumidor, bem como a importância dos programas de fidelização para que as empresas aumentem os lucros com base na criação de relações leais com os seus clientes. Neste seguimento é também estudado a forma como o blockchain pode ser uma ferramenta importante para a evolução e diferenciação dos programas de fidelização como por exemplo: integração de várias entidades, customização das características dos programas de fidelização, entre outros. Através de uma metodologia quantitativa, foi criado um modelo em linguagem de programação Python, capaz de simular o comportamento de uma amostra de indivíduos relativamente ao consumo em duas entidades distintas. Esta simulação foi realizada para um período de 24 meses, de forma a comparar o rendimento que cada entidade consegue obter, antes e após a introdução deste programa de fidelização no seu negócio. Para investigação futura, sugere-se a aplicação da metodologia proposta por um período superior a 24 meses. Além deste ponto, deve ser estudado o impacto que a alteração de cada uma das variáveis definidas ao longo do trabalho pode ter na solução final.
Loyalty programs now have a global reach, a consequence of the exponential increase in globalization and the digital age. Paradoxically, the dropout rates for these programs are very high. The saturation of the traditional concept of loyalty programs can be one of the reasons for users to use less and less these types of programs. It is, therefore, necessary to create strategies to be able to attract consumer interest in loyalty programs again. The objective of this work is to understand if the creation of a multi-entity program its benefit to all the stakeholders. This loyalty program, in order to differentiate itself from current programs of this nature, should not limit the user in the way he decides to enjoy its benefits. This program is also distinguished for simplifying the user’s usability since it aggregates several entities in a single platform. As a framework for research, the evolution of consumer needs is studied, as well as the importance of loyalty programs for companies to increase profits based on the loyalty relationship they create with their customers. In this segment, it is also studied how the blockchain can be an important tool for the evolution and differentiation of loyalty programs, such as integration of various entities, customization of the characteristics of loyalty programs, among others. Through a quantitative methodology, a Python programming language model was created, capable of simulating the behavior of a sample of individuals regarding consumption in two different entities. This simulation was carried out for a period of 24 months, in order to compare the income that each entity manages to obtain, before and after the introduction of this loyalty program in its business. For future research, it is suggested to apply the proposed methodology for a period longer than 24 months. In addition to this point, the impact that changing each of the variables defined throughout the work can have on the final solution should be studied.

During the 1740’s, Hudson Bay went from an obscure backwater of the British Empire to a locus of colonial ambition. Arthur Dobbs revitalized Northwest Passage exploration, generating new information about the region’s environment and indigenous peoples. This study explores evolving English and British representations of Hudson Bay’s climate and landscape in travel and natural history writing, and probes British anxieties about foreign environments. I demonstrate how Dobbs’ ideology of improvement optimistically re-imagined the North, opening a new discursive space wherein the Subarctic could be favourably described and colonized. I examine how Hudson Bay explorers’ responses to difficulties in the Arctic and Subarctic were seen to embody, even amplify, central principles and features of eighteenth-century British culture and identity. Finally, I investigate how latitude served as a benchmark for civilization and savagery, subjugating the Lowland Cree and Inuit to British visions of settlement and improvement in their home territories.