Orientador: Elenice Aparecida de Moraes Ferrari / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-23T06:24:39Z (GMT). No. of bitstreams: 1 Faria_LarissaOliveiraMellonide_M.pdf: 1121073 bytes, checksum: 5a3108ca0447b5fae98988b4611d7616 (MD5) Previous issue date: 2013 / Resumo: O óxido nítrico (NO) é um neurotransmissor não convencional o qual tem papel importante em processos neurobiológicos de comportamento e de memória. Sua síntese é mediada por três isoformas de sintase do óxido nítrico (NOS): a neuronal (nNOS), a endotelial (eNOS) e a induzível (iNOS). Este trabalho investigou os efeitos da administração do 7- nitroindazol (7-NI), inibidor preferencial da nNOS, na consolidação e reconsolidação da memória do condicionamento clássico aversivo. Pombos adultos foram atribuídos a 5 grupos: Foram usados 5 grupos: grupo 7-nitroindazole (7-NI) (100nmol/0.5?/l; DMSO (20%), NaOH (50mM) e Tween-80 (16%) diluído em PBS; i.c.v.), grupo veículo (VEIC) (0,5?/l; DMSO (20%), NaOH (50mM) e Tween-80 (16%) diluído em PBS, i.c.v.), grupo condicionado/não tratado (COND), grupo contexto/não-tratado (CONT) e grupo não tratado/não condicionado (NÄIVE). Sete dias após implante de microcânula intracerebroventricular (i.c.v.), ocorreu o condicionamento com três associações contextochoque numa sessão de 20 min. O teste e o re-teste consistiram na re-exposição ao contexto do condicionamento por 5 min. O intervalo entre sessões foi de 24h. A administração de 7-NI ou do veículo ocorreu imediatamente após o treino (Experimento 1) ou após o re-teste (Experimento 2). A atividade enzimática da NOS dependente e independente de Ca2+ e da expressão protéica da nNOS foram realizadas no tecido hipocampal. No Experimento 1, a ocorrência de congelamento no teste do 7-NI foi menor do que no treino (p<0.01) e no teste do COND e VEIC (p < 0.001). A atividade da NOS dependente de Ca++ no 7-NI foi menor do que no COND e VEIC (p<0,01), mas não diferiu do CONT e do NÄIVE. A expressão protéica de nNOS não diferiu entre os grupos (p<0,05). No Experimento 2, houve diminuição dos comportamentos defensivos, incluindo o congelamento, no re-teste do 7-NI comparado com VEIC e COND (p<0.05), mas os grupos não diferiram quanto à atividade de NOS dependente de Ca2+ ou à expressão protéica da nNOS. Conclui-se que o 7-NI interferiu na consolidação e a reconsolidação da memória, indicando a ativação da via de sinalização do óxido nítrico no hipocampo em processos da memória de medo condicionado ao contexto em pombos / Abstract: Nitric oxide (NO) is an unconventional neurotransmitter which plays an important role in neurobiological processes of behavior and memory. Its synthesis is mediated by three isoforms of nitric oxide synthase (NOS): the neuronal (nNOS), the endothelial (eNOS) and the inducible (iNOS). This study investigated the effects of the administration of 7- nitroindazole (7-NI), a preferential nNOS inhibitor, in the consolidation and reconsolidation of aversive classical conditioning memory. Adult male pigeons were assigned to 5 groups: 7-nitroindazole, 7-NI (100nmol/0.5?/l; DMSO (20%), NaOH (50 mM) and Tween-80 (16%) diluted in PBS; i.c.v.) Vehicle group; VEH (0.5 ? / L; DMSO (20%), NaOH (50 mM) and Tween-80 (16%) diluted in PBS; i.c.v.), conditioning/non-treated group (COND), context/non-treated group (CONT) and non-conditioning/non-treated group (NÄIVE). Seven days after implantation of intracerebral ventricular (i.c.v.) microcannula the conditioning occurred with three context-shock associations in a session of 20 min. During the testing and retesting sessions pigeons were reexposed to the conditioning context for 5 min. The between sessions interval was 24h. Administration of 7-NI or vehicle occurred immediately after training (Experiment 1) or after testing (Experiment 2). The enzymatic activity of Ca2+ dependent and independent NOS and protein expression of nNOS in the hippocampus tissue were carried out following the behavioral test or retest. In Experiment 1, the occurrence of freezing in the testing session of 7-NI group was lower than in the training (p <0.01) and the testing sessions of COND and VEH groups (p <0.001). The activity of Ca2+ dependent NOS in the 7-NI group was lower than in COND and VEH groups (p <0.01) but did not differ from CONT and NÄIVE groups. The nNOS protein expression in the hippocampus did not differ among the different groups (p<0.05). In Experiment 2, there was a decrease of defensive behaviors, which include freezing, in the retest of the 7-NI compared with VEH and COND groups (p <0.05), but the groups did not differ in the activity of Ca2+ dependent NOS or the protein expression of nNOS. We conclude that 7-NI interfered on the consolidation and reconsolidation of memory, indicating activation of the nitric oxide signaling pathway in the hippocampus and in memory processes of conditioned fear context in pigeons / Mestrado / Fisiologia / Mestra em Biologia Funcional e Molecular

No description available.

Die vorliegende Studie untersuchte emotionale Reaktionen im Experimentaldesign einer aversiven, differentiellen klassischen Konditionierung (CS = zwei männliche, neutral valente Gesichter; olfaktorischer UCS = vergorene Hefe) bei je vierzehn männlichen generalisierten Sozialphobikern (DSM-VI) und gesunden Kontrollpersonen. In Erwartung einer erhöhten Konditionierbarkeit, einer Extinktionsresistenz sowie einer Generalisierung auf störungsrelevante Fazialreize bei den Sozialphobikern wurden die konditionierten Reaktionen über subjektiv-verbale Urteile (Valenz, Erregung, Kontingenz), den Schreckreflex (M. orbicularis oculi links, Indikator subcorticaler Reizverarbeitung der Angst), die bilateral erhobene Aktivität des M. corrugator supercilii (Indikator für den negativ emotionalen Fazialausdruck) sowie die Herzrate (Indikator der allgemeinen psychophysiologischen Aktivierung) gemessen. Die Konditionierung verlief in beiden Experimentalgruppen erfolgreich (Valenz, Erregung, Kontingenz) und hypothesenkonform. Im Gegensatz zu den Gesunden resultierten für die Sozialphobiker eine erhöhte Konditionierbarkeit (Schreckreflexlatenz und -amplitude, Herzratendezeleration), eine Extinktionsresistenz (Erregung, Schreckreflexnullreaktionen, Corrugator) sowie eine Reizgeneralisierung (Erregung, Kontingenz, Schreckreflexlatenz, Corrugator, Herzratendezeleration). Die Befunde sprechen außerdem für eine unterschiedliche emotionale Reizverarbeitung über den Experimentalverlauf. Die Sozialphobiker reagierten in der Akquisition vorrangig in den Parametern Erregung, Kontingenz, Schreckreflex und Herzrate (Gesunde: Corrugator) sowie in der Extinktion hinsichtlich Erregung, Schreckreflex und Corrugator (Gesunde: Kontingenz). Das Valenzurteil ergab hingegen keine Gruppenspezifik. / The present study investigated the emotional responses of aversive differential Pavlovian conditioning with two male neutral faces as conditioned stimuli (CS) and a foul odor (fermented yeast) as unconditioned stimulus (UCS) in fourteen male generalized social phobics (DSM-VI) and healthy controls. The aim of this investigation was to examine the hypotheses of enhanced acquisition, delayed extinction and generalization of faces, as they represented socially relevant stimuli, concerning social phobics. Subjective indicators of conditioned response were valence, arousal and awareness. The startle reflex (recorded from left m. orbicularis oculi) was used as a measure of subcortical emotional processing. Bilaterally corrugator muscle activity (as an indicator of negative emotional facial response) and heart rate (as an indicator of general physiological activation) served as psychophysiological assessment of conditioning. Both groups were successfully conditioned as reflected by differential responses of all three subjective parameters. The results were consistent with the hypotheses. Compared to controls, social phobics showed an increased acquisition (startle latency and magnitude, heart rate deceleration), an extinction resistance (arousal, startle zero reactions, corrugator) as well as a generalization of CS types (arousal, awareness, startle latency, corrugator, heart rate deceleration). In addition the findings suggested that the emotional stimuli processing in participants are distinct. The social phobics in particular reacted to arousal, contingency awareness, startle and heart rate in acquisition (controls: corrugator) and to arousal, startle and corrugator in extinction (controls: awareness). There was no difference between groups regarding valence judgement.

Neural activity in dopaminergic areas such as the ventral tegmental area is influenced by timing processes, in particular by the temporal expectation of rewards during Pavlovian conditioning. Receipt of a reward at the expected time allows to compute reward-prediction errors which can drive learning in motor or cognitive structures. Reciprocally, dopamine plays an important role in the timing of external events. Several models of the dopaminergic system exist, but the substrate of temporal learning is rather unclear. In this article, we propose a neuro-computational model of the afferent network to the ventral tegmental area, including the lateral hypothalamus, the pedunculopontine nucleus, the amygdala, the ventromedial prefrontal cortex, the ventral basal ganglia (including the nucleus accumbens and the ventral pallidum), as well as the lateral habenula and the rostromedial tegmental nucleus. Based on a plausible connectivity and realistic learning rules, this neuro-computational model reproduces several experimental observations, such as the progressive cancelation of dopaminergic bursts at reward delivery, the appearance of bursts at the onset of reward-predicting cues or the influence of reward magnitude on activity in the amygdala and ventral tegmental area. While associative learning occurs primarily in the amygdala, learning of the temporal relationship between the cue and the associated reward is implemented as a dopamine-modulated coincidence detection mechanism in the nucleus accumbens.

In this study, the effects of the neonicotinoid pesticide, thiamethoxam, are examined through the Proboscis Extension Response (PER) in honey bees (Apis mellifera). PER is a form of classical conditioning applied to honey bees through scent and reward association which quantifies learning rates. Results between groups treated with thiamethoxam did not differ significantly from untreated control groups. Potential reasons for these results are discussed. The method and experimental apparatus for testing the PER assay are also discussed.

Indiana University-Purdue University Indianapolis (IUPUI) / In order to elucidate the role of classical conditioning in food and alcohol co-consumption, the present study examined: (1) the effects of alcohol odor cues on alcohol and food cravings and attentional bias (bias in selective attention toward either food or alcohol pictures relative to neutral pictures); and (2) the role of alcohol odor cue elicited cravings and attentional biases on subsequent consumption. Participants (n = 77; mean age = 30.84, SD = 9.46; 51.9% female, 83.1% Caucasian) first completed the lab portion of the study. In this portion, they were exposed to alcohol and neutral odorants, after which their food and alcohol cravings and attentional bias were assessed. Participants then received an online survey the next day, on which they reported their level of food and alcohol consumption following the lab portion of the study. Using repeated measures analysis of covariance, alcohol odor cues were differentially effective in increasing food and alcohol attentional bias and cravings (Fs= 0.06 to 2.72, ps= 0.03 to 0.81). Using logistic and multiple regressions, alcohol odor cue elicited alcohol attentional bias, food attentional bias, and food cravings were associated with later alcohol consumption, but not with later food consumption or concurrent consumption (βs = -0.28 to 0.48, ps = 0.02 to 0.99; Exp(B)s = 0.95 to 1.83, ps = 0.33 to 0.91). Overall, alcohol odor cues can become conditioned stimuli that elicit conditioned food-related and alcohol-related responses, both of which persist long enough to motivate later alcohol consumption; however, these conditioned responses might not persist long enough to motivate later food or concurrent consumption. These findings serve as a first step in clarifying the role of classical conditioning in concurrent consumption. In particular, they suggest that additional empirical investigations are needed to: (1) clarify the classical conditioning mechanisms underlying concurrent consumption; and (2) examine whether interventions targeting classical conditioning mechanisms are effective for reducing alcohol use.

No description available.

Tout au long de la vie, le cerveau développe des représentations de son environnement permettant à l’individu d’en tirer meilleur profit. Comment ces représentations se développent-elles pendant la quête de récompenses demeure un mystère. Il est raisonnable de penser que le cortex est le siège de ces représentations et que les ganglions de la base jouent un rôle important dans la maximisation des récompenses. En particulier, les neurones dopaminergiques semblent coder un signal d’erreur de prédiction de récompense. Cette thèse étudie le problème en construisant, à l’aide de l’apprentissage machine, un modèle informatique intégrant de nombreuses évidences neurologiques. Après une introduction au cadre mathématique et à quelques algorithmes de l’apprentissage machine, un survol de l’apprentissage en psychologie et en neuroscience et une revue des modèles de l’apprentissage dans les ganglions de la base, la thèse comporte trois articles. Le premier montre qu’il est possible d’apprendre à maximiser ses récompenses tout en développant de meilleures représentations des entrées. Le second article porte sur l'important problème toujours non résolu de la représentation du temps. Il démontre qu’une représentation du temps peut être acquise automatiquement dans un réseau de neurones artificiels faisant office de mémoire de travail. La représentation développée par le modèle ressemble beaucoup à l’activité de neurones corticaux dans des tâches similaires. De plus, le modèle montre que l’utilisation du signal d’erreur de récompense peut accélérer la construction de ces représentations temporelles. Finalement, il montre qu’une telle représentation acquise automatiquement dans le cortex peut fournir l’information nécessaire aux ganglions de la base pour expliquer le signal dopaminergique. Enfin, le troisième article évalue le pouvoir explicatif et prédictif du modèle sur différentes situations comme la présence ou l’absence d’un stimulus (conditionnement classique ou de trace) pendant l’attente de la récompense. En plus de faire des prédictions très intéressantes en lien avec la littérature sur les intervalles de temps, l’article révèle certaines lacunes du modèle qui devront être améliorées. Bref, cette thèse étend les modèles actuels de l’apprentissage des ganglions de la base et du système dopaminergique au développement concurrent de représentations temporelles dans le cortex et aux interactions de ces deux structures. / Throughout lifetime, the brain develops abstract representations of its environment that allow the individual to maximize his benefits. How these representations are developed while trying to acquire rewards remains a mystery. It is reasonable to assume that these representations arise in the cortex and that the basal ganglia are playing an important role in reward maximization. In particular, dopaminergic neurons appear to code a reward prediction error signal. This thesis studies the problem by constructing, using machine learning tools, a computational model that incorporates a number of relevant neurophysiological findings. After an introduction to the machine learning framework and to some of its algorithms, an overview of learning in psychology and neuroscience, and a review of models of learning in the basal ganglia, the thesis comprises three papers. The first article shows that it is possible to learn a better representation of the inputs while learning to maximize reward. The second paper addresses the important and still unresolved problem of the representation of time in the brain. The paper shows that a time representation can be acquired automatically in an artificial neural network acting like a working memory. The representation learned by the model closely resembles the activity of cortical neurons in similar tasks. Moreover, the model shows that the reward prediction error signal could accelerate the development of the temporal representation. Finally, it shows that if such a learned representation exists in the cortex, it could provide the necessary information to the basal ganglia to explain the dopaminergic signal. The third article evaluates the explanatory and predictive power of the model on the effects of differences in task conditions such as the presence or absence of a stimulus (classical versus trace conditioning) while waiting for the reward. Beyond making interesting predictions relevant to the timing literature, the paper reveals some shortcomings of the model that will need to be resolved. In summary, this thesis extends current models of reinforcement learning of the basal ganglia and the dopaminergic system to the concurrent development of representation in the cortex and to the interactions between these two regions.

O estabelecimento das memórias de longo prazo requer uma efetiva comunicação do hipocampo com o neocortex. Um mecanismo plausível envolvido na comunicação neuronal e na plasticidade sináptica é a sincronização da atividade elétrica cerebral na frequência teta. Estudos recentes mostraram que a sincronização entre os ritmos teta do hipocampo e do córtex pré-frontal aumenta durante a evocação das memórias aversivas e diminui após a extinção do aprendizado. Entretanto, outros ritmos cerebrais, como as ondas delta, também estão envolvidos nas respostas comportamentais do medo e nos processos de memória. Desta forma, o ritmo teta, que já foi bastante estudado pelo seu papel no aprendizado e na memória, e o ritmo delta, por seu envolvimento no ciclo sono-vigília, foram investigados considerando a relação causal entre eles. Ainda não está bem estabelecido como os ritmos delta e teta podem juntos contribuir nos processos cognitivos ou como os ritmos do hipocampo podem influenciar ou receber influencias da atividade cortical. Neste trabalho foi investigada a contribuição dos ritmos delta e teta em função do estado comportamental (vigília ativa ou congelamento) e do tipo de memória evocada (recente ou remota). Além disso, foi realizada uma análise de sincronia de fase para inferir a dinâmica da atividade elétrica entre o córtex pré-frontal medial, o hipocampo e o córtex visual durante a evocação das memórias de medo. Para tanto, os animais foram treinados e testados numa tarefa de condicionamento de medo ao contexto. Neste tipo de condicionamento, o animal aprende a estabelecer uma associação entre um determinado contexto (caixa de condicionamento) e um evento aversivo (choque elétrico nas patas) que ocorreu neste contexto. Quando o animal foi reintroduzido na caixa de condicionamento, o mesmo exibiu uma série de respostas condicionadas incluindo a reação de congelamento. Os resultados mostraram que os ritmos delta e teta estão relacionados de forma específica às respostas comportamentais de medo e de evocação das memórias recente e remota. Observou-se no espectro de potências uma maior contribuição do ritmo teta durante a vigília exploratória, diminuindo durante o congelamento. Neste último, os ratos apresentaram um robusto aumento da contribuição do ritmo delta. Além disso, a medida de causalidade mostrou ser dependente do estado comportamental do animal. Finalmente, um aumento da sincronia entre o hipocampo e o córtex pré-frontal foi evidenciado durante a evocação de memória recente, contraposta à diminuição durante a evocação da memória remota. Estes resultados indicam que a sincronização da atividade elétrica cerebral pode refletir uma facilitação na comunicação neuronal / The establishment of long-term memories requires effective communication of the hippocampus to the neocortex. Electrophysiological activities between hippocampus and prefrontal cortex have shown higher theta synchronization during retrieval of aversive memories and lower during extinction learning. While theta activity is more differently related to learning and memory, delta waves have been more discussed in the context of sleep or \"offline\" states. Few studies have investigated delta waves during \"on-line\" states (such as task-relevant situations) and the contribution of these rhythms to memory storage remains unclear. We recorded electrophysiological data to study the contributions of delta and theta waves in cortico-hippocampal system of rats underwent to contextual fear conditioning. Our experiment consisted of environmental pre-exposition, training with electrical footshocks, and recent/remote memory tests. Two groups of rats were tested one or eighteen days post training for recent or remote memory, respectively. Local field potential time series of two behavioral states were sampled: active exploration and freezing. The results showed that theta and delta rhythms play an important role in behavioral responses and memory processing. They are related to fear recall and their contribution depend on the recent or remote memory. Additionally, using an order parameter we show that theta contribution is strongly pronounced in active exploration, decreasing during freezing. In the latter, the rats presented pronounced delta waves in freezing. Moreover, a behavioral-dependent causality measure showed an increase of theta influence in delta rhythms, resulting in a theta slowing in aversive memory retrieval. Finally, we show an increased synchrony between hippocampus and prefrontal cortex during recall of recent memory, but a decreased synchrony in remote memory. We proposed that synchronized activity may facilitate the communication of information and once the memories are established in the neocortex, the synchronization decreases, and recalling them becomes more independent of the hippocampus. We proposed that delta-theta oscillations of the hippocampus over neocortical areas reflect information processing during aversive memory retrieval

Tout au long de la vie, le cerveau développe des représentations de son environnement permettant à l’individu d’en tirer meilleur profit. Comment ces représentations se développent-elles pendant la quête de récompenses demeure un mystère. Il est raisonnable de penser que le cortex est le siège de ces représentations et que les ganglions de la base jouent un rôle important dans la maximisation des récompenses. En particulier, les neurones dopaminergiques semblent coder un signal d’erreur de prédiction de récompense. Cette thèse étudie le problème en construisant, à l’aide de l’apprentissage machine, un modèle informatique intégrant de nombreuses évidences neurologiques. Après une introduction au cadre mathématique et à quelques algorithmes de l’apprentissage machine, un survol de l’apprentissage en psychologie et en neuroscience et une revue des modèles de l’apprentissage dans les ganglions de la base, la thèse comporte trois articles. Le premier montre qu’il est possible d’apprendre à maximiser ses récompenses tout en développant de meilleures représentations des entrées. Le second article porte sur l'important problème toujours non résolu de la représentation du temps. Il démontre qu’une représentation du temps peut être acquise automatiquement dans un réseau de neurones artificiels faisant office de mémoire de travail. La représentation développée par le modèle ressemble beaucoup à l’activité de neurones corticaux dans des tâches similaires. De plus, le modèle montre que l’utilisation du signal d’erreur de récompense peut accélérer la construction de ces représentations temporelles. Finalement, il montre qu’une telle représentation acquise automatiquement dans le cortex peut fournir l’information nécessaire aux ganglions de la base pour expliquer le signal dopaminergique. Enfin, le troisième article évalue le pouvoir explicatif et prédictif du modèle sur différentes situations comme la présence ou l’absence d’un stimulus (conditionnement classique ou de trace) pendant l’attente de la récompense. En plus de faire des prédictions très intéressantes en lien avec la littérature sur les intervalles de temps, l’article révèle certaines lacunes du modèle qui devront être améliorées. Bref, cette thèse étend les modèles actuels de l’apprentissage des ganglions de la base et du système dopaminergique au développement concurrent de représentations temporelles dans le cortex et aux interactions de ces deux structures. / Throughout lifetime, the brain develops abstract representations of its environment that allow the individual to maximize his benefits. How these representations are developed while trying to acquire rewards remains a mystery. It is reasonable to assume that these representations arise in the cortex and that the basal ganglia are playing an important role in reward maximization. In particular, dopaminergic neurons appear to code a reward prediction error signal. This thesis studies the problem by constructing, using machine learning tools, a computational model that incorporates a number of relevant neurophysiological findings. After an introduction to the machine learning framework and to some of its algorithms, an overview of learning in psychology and neuroscience, and a review of models of learning in the basal ganglia, the thesis comprises three papers. The first article shows that it is possible to learn a better representation of the inputs while learning to maximize reward. The second paper addresses the important and still unresolved problem of the representation of time in the brain. The paper shows that a time representation can be acquired automatically in an artificial neural network acting like a working memory. The representation learned by the model closely resembles the activity of cortical neurons in similar tasks. Moreover, the model shows that the reward prediction error signal could accelerate the development of the temporal representation. Finally, it shows that if such a learned representation exists in the cortex, it could provide the necessary information to the basal ganglia to explain the dopaminergic signal. The third article evaluates the explanatory and predictive power of the model on the effects of differences in task conditions such as the presence or absence of a stimulus (classical versus trace conditioning) while waiting for the reward. Beyond making interesting predictions relevant to the timing literature, the paper reveals some shortcomings of the model that will need to be resolved. In summary, this thesis extends current models of reinforcement learning of the basal ganglia and the dopaminergic system to the concurrent development of representation in the cortex and to the interactions between these two regions.