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1.
Nat Commun ; 12(1): 1200, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33619256

RESUMO

Learning-activated engram neurons play a critical role in memory recall. An untested hypothesis is that these same neurons play an instructive role in offline memory consolidation. Here we show that a visually-cued fear memory is consolidated during post-conditioning sleep in mice. We then use TRAP (targeted recombination in active populations) to genetically label or optogenetically manipulate primary visual cortex (V1) neurons responsive to the visual cue. Following fear conditioning, mice respond to activation of this visual engram population in a manner similar to visual presentation of fear cues. Cue-responsive neurons are selectively reactivated in V1 during post-conditioning sleep. Mimicking visual engram reactivation optogenetically leads to increased representation of the visual cue in V1. Optogenetic inhibition of the engram population during post-conditioning sleep disrupts consolidation of fear memory. We conclude that selective sleep-associated reactivation of learning-activated sensory populations serves as a necessary instructive mechanism for memory consolidation.


Assuntos
Medo/fisiologia , Consolidação da Memória/fisiologia , Memória/fisiologia , Sono/fisiologia , Animais , Condicionamento Psicológico/fisiologia , Sinais (Psicologia) , Eletrodos , Tecnologia de Fibra Óptica , Camundongos Transgênicos , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Optogenética , Privação do Sono/fisiopatologia , Córtex Visual/fisiopatologia
2.
Behav Processes ; 184: 104319, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33450315

RESUMO

Two Pavlovian appetitive conditioning experiments with rats assessed extinction cue (EC) transfer using spontaneous recovery tests. In each experiment, after conditioned stimulus (CS) A-US pairings, an EC (X) was presented during A-extinction, followed by spontaneous recovery testing with A. Experiment 1 tested for transfer between ECs; the additional CS (B) was conditioned and then was extinguished with a second EC (Y). CS A was tested with X and with Y (the possible transfer EC). Experiment 2 tested for transfer between an EC and an explicitly trained serial negative occasion setter (OS). Prior to testing with A, Y was trained in a serial Y→C-, C + discrimination; a Z→B-, B + discrimination was also trained. A was tested with X and with Y (with Y as the possible transfer OS). X and Y were also tested with B (where X with B tests possible EC-OS transfer). In each experiment Y did not reduce spontaneous recovery to A, showing no transfer of one EC to another (Experiment 1) and no transfer of a serial negative OS to a CS (A) extinguished with an EC (X; Experiment 2). X did not reduce responding to B, showing no transfer of an EC to the target CS of a serial negative OS discrimination, although Y did transfer to B (Experiment 2) showing transfer between serial OSs. X did reduce responding to the CS (A) it had occurred with during extinction (Experiments 1 and 2). The results are discussed in terms of EC characteristics and regarding theories of an EC's possible mechanisms.


Assuntos
Sinais (Psicologia) , Extinção Psicológica , Animais , Condicionamento Clássico , Condicionamento Operante , Condicionamento Psicológico , Ratos
3.
Neuroimage ; 227: 117629, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33316390

RESUMO

The neural processes that support inhibitory control in the face of stimuli with a history of reward association are not yet well understood. Yet, the ability to flexibly adapt behavior to changing reward-contingency contexts is important for daily functioning and warrants further investigation. This study aimed to characterize neural and behavioral impacts of stimuli with a history of conditioned reward association on motor inhibitory control in healthy young adults by investigating group-level effects as well as individual variation in the ability to inhibit responses to stimuli with a reward history. Participants (N = 41) first completed a reward conditioning phase, during which responses to rewarded stimuli were associated with money and responses to unrewarded stimuli were not. Rewarded and unrewarded stimuli from training were carried forward as No-Go targets in a subsequent go/no-go task to test the effect of reward history on inhibitory control. Participants underwent functional brain imaging during the go/no-go portion of the task. On average, a history of reward conditioning disrupted inhibitory control. Compared to inhibition of responses to stimuli with no reward history, trials that required inhibition of responses to previously rewarded stimuli were associated with greater activity in frontal and striatal regions, including the inferior frontal gyrus, insula, striatum, and thalamus. Activity in the insula and thalamus during false alarms and in the ventromedial prefrontal cortex during correctly withheld trials predicted behavioral performance on the task. Overall, these results suggest that reward history serves to disrupt inhibitory control and provide evidence for diverging roles of the insula and ventromedial prefrontal cortex while inhibiting responses to stimuli with a reward history.


Assuntos
Encéfalo/diagnóstico por imagem , Condicionamento Psicológico/fisiologia , Inibição Psicológica , Recompensa , Adolescente , Adulto , Encéfalo/fisiologia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
4.
Edumecentro ; 12(4): 73-88, oct.-dic. 2020.
Artigo em Espanhol | LILACS | ID: biblio-1142850

RESUMO

RESUMEN Fundamento: la enseñanza de estrategias de aprendizaje constituye una vía para lograr un pensamiento que promueva la ejecución independiente y creadora del alumno. Objetivo: diseñar una estrategia didáctica destinada a favorecer el desarrollo de estrategias de aprendizaje afectivo-motivacionales en los estudiantes de Estomatología desde la disciplina Morfofisiología. Métodos: se realizó una investigación observacional descriptiva transversal en la Facultad de Estomatología de la Universidad de Ciencias Médicas de Camagüey, durante el período septiembre 2016-junio 2017. Se aplicaron métodos teóricos generales y entre los empíricos: tres cuestionarios a estudiantes, entre ellos: el de autoinforme Motivación académica y estrategias de aprendizaje y la Escala de Estrategias de Aprendizaje ACRA-A. Resultados: se realizó un diagnóstico del estado actual del desarrollo de estrategias de aprendizaje afectivo-motivacionales en los estudiantes de primer año de Estomatología, lo que permitió determinar que existen fortalezas y debilidades en cuanto a la problemática investigada, a partir de las cuales se diseñó una estrategia didáctica concebida en cuatro etapas, cada una de ellas contiene un conjunto de acciones a desarrollar. Fue valorada por criterio de especialistas a través del método de talleres de opinión crítica y construcción colectiva. Conclusiones: los especialistas consultados la consideraron adecuada para su aplicación porque constituye un valioso instrumento para favorecer el desarrollo de estrategias de aprendizaje afectivo-motivacionales, lo que influirá de manera positiva en el proceso de aprendizaje en la Morfofisiología.


ABSTRACT Background: the teaching of learning strategies contributes to achieve a way of thinking that promotes the independent and creative performance of the student. Objective: to design a didactic strategy aimed to favor the development of affective-motivational learning strategies in Dentistry students through the Morphology-physiology discipline. Methods: a cross-sectional descriptive observational research work was carried out in the Faculty of dentistry of Camagüey University of Medical Sciences, from September 2016 to June 2017. General theoretical methods were used and among the empirical ones: three questionnaires to students, among them: the self-report Academic motivation and learning strategies and the ACRA-A Learning Strategies Scale. Results: a diagnosis was made of the current state of the development of affective-motivational learning strategies in first-year Dentistry students, which allowed determining that there are strengths and weaknesses in terms of the investigated problem, from which it was designed a didactic strategy conceived in four stages, each one containing a set of actions to be developed. It was assessed by the criteria of specialists through the method of critical opinion workshops and collective construction. Conclusions: the specialists consulted considered it adequate for its implementation because it constitutes a valuable instrument to favor the development of affective-motivational learning strategies, which will positively influence the learning process in Morphology-physiology.


Assuntos
Estudantes de Odontologia , Estratégias , Condicionamento Psicológico , Educação Médica , Aprendizagem
5.
PLoS One ; 15(12): e0227462, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382701

RESUMO

An age-old hypothesis proposes that object motion across the receptor surface organizes sensory maps (Lotze, 19th century). Skin patches learn their relative positions from the order in which they are stimulated during motion events. We propose that reversing the local motion within a global motion sequence ('motion scrambling') provides a good test for this idea, and present results of the first experiment implementing the paradigm. We used 6-point apparent motion along the forearm. In the Scrambled sequence, two middle locations were touched in reversed order (1-2-4-3-5-6, followed by 6-5-3-4-2-1, in a continuous loop). This created a double U-turn within an otherwise constant-velocity motion, as if skin patches 3 and 4 physically swapped locations. The control condition, Orderly, proceeded at constant velocity at inter-stimulus onset interval of 120 ms. The 26.4-minute conditioning (delivered in twenty-four 66-s bouts) was interspersed with testing of perceived motion direction between the two middle tactors presented on their own (sequence 3-4 or 4-3). Our twenty participants reported motion direction. Direction discrimination was degraded following exposure to Scrambled pattern and was 0.31 d' weaker than following Orderly conditioning (p = .007). Consistent with the proposed role of motion, this could be the beginning of re-learning of relative positions. An alternative explanation is that greater speed adaptation occurred in the Scrambled pattern, raising direction threshold. In future studies, longer conditioning should tease apart the two explanations: our re-mapping hypothesis predicts an overall reversal in perceived motion direction between critical locations (for either motion direction), whereas the speed adaptation alternative predicts chance-level performance at worst, without reversing.


Assuntos
Adaptação Fisiológica , Condicionamento Psicológico , Percepção de Movimento/fisiologia , Percepção do Tato/fisiologia , Tato/fisiologia , Adolescente , Adulto , Fenômenos Biomecânicos/fisiologia , Feminino , Antebraço/inervação , Antebraço/fisiologia , Humanos , Masculino , Movimento (Física) , Psicofísica/métodos , Pele/inervação , Fenômenos Fisiológicos da Pele
6.
PLoS One ; 15(12): e0225023, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33326450

RESUMO

Dog training methods range broadly from those using mostly positive punishment and negative reinforcement (aversive-based) to those using primarily positive reinforcement (reward-based). Although aversive-based training has been strongly criticized for negatively affecting dog welfare, there is no comprehensive research focusing on companion dogs and mainstream techniques, and most studies rely on owner-reported assessment of training methods and dog behavior. The aim of the present study was to evaluate the effects of aversive- and reward-based training methods on companion dog welfare within and outside the training context. Ninety-two companion dogs were recruited from three reward-based schools (Group Reward, n = 42), and from four aversive-based schools, two using low proportions of aversive-based methods (Group Mixed, n = 22) and two using high proportions of aversive-based methods (Group Aversive, n = 28). For evaluating welfare during training, dogs were video recorded for three sessions and six saliva samples were collected, three at home (baseline levels) and three after training (post-training levels). Video recordings were used to examine the frequency of stress-related behaviors (e.g., lip lick, yawn) and the overall behavioral state of the dog (e.g., tense, relaxed), and saliva samples were analyzed for cortisol concentration. For evaluating welfare outside the training context, dogs participated in a cognitive bias task. Results showed that dogs from Group Aversive displayed more stress-related behaviors, were more frequently in tense and low behavioral states and panted more during training, and exhibited higher post-training increases in cortisol levels than dogs from Group Reward. Additionally, dogs from Group Aversive were more 'pessimistic' in the cognitive bias task than dogs from Group Reward. Dogs from Group Mixed displayed more stress-related behaviors, were more frequently in tense states and panted more during training than dogs from Group Reward. Finally, although Groups Mixed and Aversive did not differ in their performance in the cognitive bias task nor in cortisol levels, the former displayed more stress-related behaviors and was more frequently in tense and low behavioral states. These findings indicate that aversive-based training methods, especially if used in high proportions, compromise the welfare of companion dogs both within and outside the training context.


Assuntos
Animais de Estimação/psicologia , Reforço Psicológico , Afeto/fisiologia , Animais , Comportamento Animal/fisiologia , Condicionamento Psicológico/fisiologia , Cães , Humanos , Hidrocortisona/análise , Masculino , Punição/psicologia , Recompensa , Saliva/química , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Inquéritos e Questionários , Gravação em Vídeo
7.
Nat Commun ; 11(1): 5180, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057013

RESUMO

Fear and extinction learning are adaptive processes caused by molecular changes in specific neural circuits. Neurons expressing the corticotropin-releasing hormone gene (Crh) in central amygdala (CeA) are implicated in threat regulation, yet little is known of cell type-specific gene pathways mediating adaptive learning. We translationally profiled the transcriptome of CeA Crh-expressing cells (Crh neurons) after fear conditioning or extinction in mice using translating ribosome affinity purification (TRAP) and RNAseq. Differential gene expression and co-expression network analyses identified diverse networks activated or inhibited by fear vs extinction. Upstream regulator analysis demonstrated that extinction associates with reduced CREB expression, and viral vector-induced increased CREB expression in Crh neurons increased fear expression and inhibited extinction. These findings suggest that CREB, within CeA Crh neurons, may function as a molecular switch that regulates expression of fear and its extinction. Cell-type specific translational analyses may suggest targets useful for understanding and treating stress-related psychiatric illness.


Assuntos
Núcleo Central da Amígdala/fisiologia , Condicionamento Psicológico/fisiologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Extinção Psicológica/fisiologia , Medo/fisiologia , Animais , Comportamento Animal , Núcleo Central da Amígdala/citologia , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Modelos Animais , Neurônios/metabolismo , RNA-Seq
8.
J Vis Exp ; (162)2020 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-32894260

RESUMO

Emotional memory has been primarily studied with fear-conditioning paradigms. Fear conditioning is a form of learning through which individuals learn the relationships between aversive events and otherwise neutral stimuli. The most-widely utilized procedures for studying emotional memories entail fear conditioning in rats. In these tasks, the unconditioned stimulus (US) is a footshock presented once or several times across single or several sessions, and the conditioned response (CR) is freezing. In a version of these procedures, called cued fear conditioning, a tone (conditioned stimulus, CS) is paired with footshocks (US) during the training phase. During the first test, animals are exposed to the same context in which training took place, and freezing responses are tested in the absence of footshocks and tones (i.e., a context test). During the second test, freezing is measured when the context is changed (e.g., by manipulating the smell and walls of the experimental chamber) and the tone is presented in the absence of footshocks (i.e., a cue test). Most cued fear conditioning procedures entail few tone-shock pairings (e.g., 1-3 trials in a single session). There is a growing interest in less common versions involving an extensive number of pairings (i.e., overtraining) related to the long-lasting effect called fear incubation (i.e., fear responses increase over time without further exposure to aversive events or conditioned stimuli). Extended fear-conditioning tasks have been key to the understanding of fear incubation's behavioral and neurobiological aspects, including its relationship with other psychological phenomena (e.g., post-traumatic stress disorder). Here, we describe an extended fear-conditioning protocol that produces overtraining and fear incubation in rats. This protocol entails a single training session with 25 tone-shock pairings (i.e., overtraining) and a comparison of conditioned freezing responses during context and cue tests 48 h (short-term) and 6 weeks (long-term) after training.


Assuntos
Condicionamento Psicológico , Medo/fisiologia , Estimulação Acústica , Animais , Sinais (Psicologia) , Masculino , Memória/fisiologia , Ratos , Fatores de Tempo
9.
Life Sci ; 260: 118430, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32931800

RESUMO

AIMS: Previous investigations demonstrated that tramadol, as a painkiller, similar to morphine induces tolerance and dependence. Furthermore, the cannabinoid receptor 1 (CB1R) located in the nucleus accumbens (NAc) plays a critical role in morphine-induced conditioning. Therefore, the main objective of this study was to evaluate the role of NAc CB1R in tramadol induced conditioning and reinstatement. MAIN METHODS: In the present experiment, the effect of NAc CB1 receptors on tramadol induced conditioning was tested by microinjecting of arachidonylcyclopropylamide (ACPA, CB1R agonist) and AM 251 (CB1R inverse agonist) in the NAc during tramadol-induced conditioning in the adult male Wistar rats. In addition, the role of NAc CB1R in the reinstatement was also evaluated by injecting ACPA and AM 251 after a 10-days extinction period. KEY FINDINGS: The obtained data revealed that the administration of tramadol (1,2, and 4 mg/kg, ip) dose-dependently produced conditioned place preference (CPP). Moreover, intra-NAc administration of ACPA (0.25, 0.5, and 1 µg/rat) dose-dependently induced conditioning, while the administration of AM-251 (30, 60, and 120 ng/rat) induced a significant aversion. In addition, the administration of a non-effective dose of AM251 during tramadol conditioning inhibited conditioning induced by tramadol. On the other hand, the administration of ACPA after extinction induced a significant reinstatement. Notably, the locomotor activity did not change among groups. SIGNIFICANCE: Previous studies have shown that tramadol-induced CPP occurs through µ-opioid receptors. The data obtained in the current study indicated that CB1R located in the NAc is involved in mediating conditioning induced by tramadol. Besides, CB1R also plays a vital role in the reinstatement of tramadol-conditioned animals. It might be due to the effect of opioids on enhancing the level of CB1R.


Assuntos
Analgésicos Opioides/efeitos adversos , Condicionamento Psicológico/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Receptor CB1 de Canabinoide/fisiologia , Tramadol/efeitos adversos , Analgésicos Opioides/administração & dosagem , Animais , Condicionamento Clássico , Relação Dose-Resposta a Droga , Extinção Psicológica/efeitos dos fármacos , Masculino , Núcleo Accumbens/metabolismo , Piperidinas/administração & dosagem , Piperidinas/farmacologia , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Ratos Wistar , Receptor CB1 de Canabinoide/agonistas , Tramadol/administração & dosagem
10.
Nat Commun ; 11(1): 4358, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868768

RESUMO

Learned fear and safety are associated with distinct oscillatory states in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC). To determine if and how these network states support the retrieval of competing memories, we mimicked endogenous oscillatory activity through optogenetic stimulation of parvalbumin-expressing interneurons in mice during retrieval of contextual fear and extinction memories. We found that exogenously induced 4 Hz and 8 Hz oscillatory activity in the BLA exerts bi-directional control over conditioned freezing behavior in an experience- and context-specific manner, and that these oscillations have an experience-dependent ability to recruit distinct functional neuronal ensembles. At the network level we demonstrate, via simultaneous manipulation of BLA and mPFC, that experience-dependent 4 Hz resonance across BLA-mPFC circuitry supports post-extinction fear memory retrieval. Our findings reveal that post-extinction fear memory retrieval is supported by local and interregional experience-dependent resonance, and suggest novel approaches for interrogation and therapeutic manipulation of acquired fear circuitry.


Assuntos
Tonsila do Cerebelo/fisiologia , Extinção Psicológica , Medo/fisiologia , Memória/fisiologia , Animais , Complexo Nuclear Basolateral da Amígdala/fisiologia , Condicionamento Psicológico , Eletrofisiologia/métodos , Aprendizagem/fisiologia , Camundongos , Optogenética/métodos , Córtex Pré-Frontal/fisiologia
11.
Life Sci ; 259: 118271, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798553

RESUMO

AIMS: Cannabidiolic acid (CBDA) is one of the most abundant phytocannabinoid acids in the Cannabis sativa plant. It has been shown that it is able to exert some therapeutic effects such as antiemetic, anti-inflammatory, anxiolytic or antidepressant, although some of them remain under debate. In the present study we aim to assess the potential behavioural effects of CBDA as well as its modulation of neuroinflammatory markers in the prefrontal cortex (PFC). MAIN METHODS: The effects of acute and repeated CBDA (0.001-1 mg/kg i.p.) treatments were evaluated on cognitive, emotional, motivational and nociceptive behaviours in male CD1 mice. For this, Y-maze and elevated plus maze paradigms, spontaneous locomotor activity, social interaction, hot-plate, formalin and tail suspension tests were used. We also studied the effects of CBDA on the rewarding responses of cocaine in the conditioned place preference (CPP) paradigm. Finally, PFC was dissected after acute and repeated CBDA treatments to evaluate inflammatory markers. KEY FINDINGS: Acute CBDA treatment induced antinociceptive responses in the hot-plate test. A 10-day CBDA treatment reduced despair-like behaviour in the tail suspension test. CBDA did not alter the results of the remaining behavioural tests assayed, including cocaine-induced reward in the CPP. Regarding the biochemical analysis, repeated CBDA treatment diminished the level of peroxisome proliferator-activated receptor gamma (PPAR-γ) and increased that of interleukin-6 (IL-6) protein in PFC. SIGNIFICANCE: These results show that CBDA has limited in vivo effects on the modulation of mice behaviour, supporting the current skepticism regarding its therapeutic potential.


Assuntos
Comportamento Animal/efeitos dos fármacos , Canabinoides/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Animais , Ansiolíticos/farmacologia , Antieméticos/farmacologia , Canabinoides/metabolismo , Cannabis/efeitos dos fármacos , Cognição/efeitos dos fármacos , Condicionamento Psicológico/efeitos dos fármacos , Dronabinol/farmacologia , Emoções/efeitos dos fármacos , Cloreto de Lítio/farmacologia , Masculino , Camundongos , Motivação/efeitos dos fármacos , Nociceptores/efeitos dos fármacos
12.
Nat Commun ; 11(1): 4220, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32839437

RESUMO

Post-traumatic stress disorder (PTSD) is characterized by emotional hypermnesia on which preclinical studies focus so far. While this hypermnesia relates to salient traumatic cues, partial amnesia for the traumatic context can also be observed. Here, we show in mice that contextual amnesia is causally involved in PTSD-like memory formation, and that treating the amnesia by re-exposure to all trauma-related cues cures PTSD-like hypermnesia. These findings open a therapeutic perspective based on trauma contextualization and the underlying hippocampal mechanisms.


Assuntos
Amnésia/prevenção & controle , Amnésia/terapia , Condicionamento Psicológico/fisiologia , Memória/fisiologia , Transtornos de Estresse Pós-Traumáticos/prevenção & controle , Transtornos de Estresse Pós-Traumáticos/terapia , Amnésia/fisiopatologia , Animais , Aprendizagem da Esquiva/fisiologia , Sinais (Psicologia) , Emoções , Hipocampo/fisiopatologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Transtornos de Estresse Pós-Traumáticos/fisiopatologia
13.
PLoS One ; 15(7): e0236039, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32702030

RESUMO

BACKGROUND: The bidirectional selection of high and low anxiety-like behavior is a valuable tool for understanding the neurocircuits that are responsible for anxiety disorders. Our group developed two breeding lines of rats, known as Carioca High- and Low-conditioned Freezing (CHF and CLF), based on defensive freezing in the contextual fear conditioning paradigm. A random selected line was employed as a control (CTL) comparison group for both CHF and CLF lines of animals. The present study performed Fos immunochemistry to investigate changes in neural activity in different brain structures among CHF and CLF rats when they were exposed to contextual cues that were previously associated with footshock. RESULTS: The study indicated that CHF rats expressed high Fos expression in the locus coeruleus, periventricular nucleus of the hypothalamus (PVN), and lateral portion of the septal area and low Fos expression in the medial portion of the septal area, dentate gyrus, and prelimbic cortex (PL) compared to CTL animals. CLF rats exhibited a decrease in Fos expression in the PVN, PL, and basolateral nucleus of the amygdala and increase in the cingulate and perirhinal cortices compared to CTL animals. CONCLUSIONS: Both CHF and CLF rats displayed Fos expression changes key regions of the anxiety brain circuitry. The two bidirectional lines exhibit different pattern of neural activation and inhibition with opposing influences on the PVN, the main structure involved in regulating the hypothalamic-pituitary-adrenal neuroendocrine responses observed in anxiety disorders.


Assuntos
Encéfalo/metabolismo , Condicionamento Psicológico , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Ansiedade/metabolismo , Ansiedade/psicologia , Masculino , Ratos
14.
Nat Commun ; 11(1): 3688, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703948

RESUMO

Zeta inhibitory peptide (ZIP), a PKMζ inhibitor, is widely used to interfere with the maintenance of acquired memories. ZIP is able to erase memory even in the absence of PKMζ, via an unknown mechanism. We found that ZIP induces redistribution of the AMPARGluA1 in HEK293 cells and primary cortical neurons, and decreases AMPAR-mediated currents in the nucleus accumbens (NAc). These effects were mimicked by free arginine or by a modified ZIP in which all but the arginine residues were replaced by alanine. Redistribution was blocked by a peptidase-resistant version of ZIP and by treatment with the nitric oxide (NO)-synthase inhibitor L-NAME. ZIP increased GluA1-S831 phosphorylation and ZIP-induced redistribution was blocked by nitrosyl-mutant GluA1-C875S or serine-mutant GluA1-S831A. Introducing the cleavable arginine-alanine peptide into the NAc attenuated expression of cocaine-conditioned reward. Together, these results suggest that ZIP may act as an arginine donor, facilitating NO-dependent downregulation of AMPARs, thereby attenuating learning and memory.


Assuntos
Peptídeos Penetradores de Células/farmacologia , Condicionamento Psicológico/efeitos dos fármacos , Lipopeptídeos/farmacologia , Memória de Longo Prazo/efeitos dos fármacos , Óxido Nítrico/metabolismo , Receptores de AMPA/metabolismo , Animais , Cocaína/administração & dosagem , Regulação para Baixo , Endocitose/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Células HEK293 , Humanos , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Camundongos , Modelos Animais , NG-Nitroarginina Metil Éster/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Óxido Nítrico/antagonistas & inibidores , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/fisiologia , Fosforilação , Cultura Primária de Células , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/metabolismo , Ratos , Receptores de AMPA/genética , Recompensa , Técnicas Estereotáxicas
15.
Neuron ; 107(3): 552-565.e10, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502462

RESUMO

The occurrence of dreaming during rapid eye movement (REM) sleep prompts interest in the role of REM sleep in hippocampal-dependent episodic memory. Within the mammalian hippocampus, the dentate gyrus (DG) has the unique characteristic of exhibiting neurogenesis persisting into adulthood. Despite their small numbers and sparse activity, adult-born neurons (ABNs) in the DG play critical roles in memory; however, their memory function during sleep is unknown. Here, we investigate whether young ABN activity contributes to memory consolidation during sleep using Ca2+ imaging in freely moving mice. We found that contextual fear learning recruits a population of young ABNs that are reactivated during subsequent REM sleep against a backdrop of overall reduced ABN activity. Optogenetic silencing of this sparse ABN activity during REM sleep alters the structural remodeling of spines on ABN dendrites and impairs memory consolidation. These findings provide a causal link between ABN activity during REM sleep and memory consolidation.


Assuntos
Condicionamento Psicológico , Giro Denteado/fisiologia , Consolidação da Memória/fisiologia , Neurônios/fisiologia , Sono REM/fisiologia , Animais , Cálcio/metabolismo , Giro Denteado/citologia , Eletroencefalografia , Eletromiografia , Medo , Hipocampo , Aprendizagem , Camundongos , Neurogênese , Optogenética , Ritmo Teta
17.
Sci Rep ; 10(1): 7872, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398687

RESUMO

The ability to move towards or away from a light source, namely phototaxis, is essential for a number of species to find the right environmental niche and may have driven the appearance of simple visual systems. In this study we ask if the later evolution of more complex visual systems was accompanied by a sophistication of phototactic behaviour. The honey bee is an ideal model organism to tackle this question, as it has an elaborate visual system, demonstrates exquisite abilities for visual learning and performs phototaxis. Our data suggest that in this insect, phototaxis has wavelength specific properties and is a highly dynamical response including multiple decision steps. In addition, we show that previous experience with a light (through exposure or classical aversive conditioning) modulates the phototactic response. This plasticity is dependent on the wavelength used, with blue being more labile than green or ultraviolet. Wavelength, intensity and past experience are integrated into an overall valence for each light that determines phototactic behaviour in honey bees. Thus, our results support the idea that complex visual systems allow sophisticated phototaxis. Future studies could take advantage of these findings to better understand the neuronal circuits underlying this processing of the visual information.


Assuntos
Abelhas/fisiologia , Percepção de Cores/fisiologia , Visão de Cores/fisiologia , Fototaxia/fisiologia , Percepção Visual/fisiologia , Animais , Aprendizagem por Associação/fisiologia , Visão de Cores/efeitos da radiação , Condicionamento Psicológico/fisiologia , Discriminação Psicológica/fisiologia , Discriminação Psicológica/efeitos da radiação , Luz , Estimulação Luminosa , Células Fotorreceptoras de Invertebrados/fisiologia , Fototaxia/efeitos da radiação
18.
Sci Rep ; 10(1): 7627, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32376865

RESUMO

When a cue no longer predicts a threat, a diminished ability to extinguish or reverse this association is thought to increase risk for stress-related disorders. Despite the clear clinical relevance, the mediating neurochemical mechanisms of threat reversal have received relatively little study. One neurotransmitter implicated in rodent research of changing associations with threat is dopamine. To study whether dopamine is involved in threat reversal in humans, we used high-resolution positron emission tomography (PET) coupled with 18F-fallypride. Twelve healthy volunteers (6 F/6 M) underwent three PET scans: (i) at baseline, (ii) following threat conditioning (the response to a cue associated with electric wrist shock), and (iii) following threat reversal (the response to the same cue now associated with safety). We observed moderate evidence of reduced dopamine D2/3 receptor availability, consistent with greater dopamine release, in the bilateral anterior hippocampus following threat reversal, in response to a safety cue that was previously associated with threat, as compared to both baseline and during exposure to the same cue prior to threat reversal. These findings offer the first preliminary evidence that the response to a previously threatening cue that has since become associated with safety involves dopaminergic neurotransmission within the hippocampus in healthy humans.


Assuntos
Dopamina/metabolismo , Hipocampo/metabolismo , Plasticidade Neuronal , Adulto , Condicionamento Psicológico , Sinais (Psicologia) , Feminino , Voluntários Saudáveis , Hipocampo/diagnóstico por imagem , Hipocampo/fisiologia , Humanos , Masculino , Tomografia por Emissão de Pósitrons
19.
Nihon Yakurigaku Zasshi ; 155(3): 135-139, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32378629

RESUMO

Stress potentiates craving for addictive drugs including cocaine. To elucidate neural mechanisms underlying this effect of stress, we developed an experimental paradigm combining cocaine-induced conditioned place preference (CPP) with a restraint stress. Acute restraint stress exposure immediately before posttest significantly increased cocaine CPP scores. It has been suggested that the extracellular noradrenaline (NA) level is increased by stress in the laterodorsal tegmental nucleus (LDT), which sends cholinergic projections to dopamine (DA) neurons in the ventral tegmental area (VTA), and medial prefrontal cortex (mPFC), which receives DA input from the VTA. Thus, we investigated the roles of NA in these brain regions. Intra-LDT injection of an α2 or a ß adrenoceptor antagonist attenuated the stress-induced enhancement of cocaine CPP. In vitro whole-cell recordings revealed that α2 adrenoceptor stimulation reduced GABAergic inputs to LDT cholinergic neurons that were obtained from cocaine-, but not saline-, treated rats. On the other hand, α1, but not α2 or ß, adrenoceptor stimulation excited mPFC pyramidal neurons. Intra-mPFC injection of an α1 adrenoceptor antagonist attenuated the stress-induced enhancement of cocaine CPP. Additionally, chemogenetic silencing of mPFC excitatory neurons also reduced the stress-induced enhancement of cocaine CPP. These findings suggest that stress-induced increases in neuronal activity of the LDT and mPFC may contribute to the enhancement of cocaine craving.


Assuntos
Neurônios Colinérgicos/patologia , Cocaína , Fissura , Estresse Psicológico , Animais , Condicionamento Psicológico , Norepinefrina/análise , Córtex Pré-Frontal , Ratos , Ratos Sprague-Dawley , Restrição Física , Tegmento Mesencefálico
20.
Cochrane Database Syst Rev ; 5: CD008552, 2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32449203

RESUMO

BACKGROUND: Insufficient consumption of fruits and vegetables in childhood increases the risk of future non-communicable diseases, including cardiovascular disease. Testing the effects of interventions to increase consumption of fruit and vegetables, including those focused on specific child-feeding strategies or broader multicomponent interventions targeting the home or childcare environment is required to assess the potential to reduce this disease burden. OBJECTIVES: To assess the effectiveness, cost effectiveness and associated adverse events of interventions designed to increase the consumption of fruit, vegetables or both amongst children aged five years and under. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and two clinical trials registries to identify eligible trials on 25 January 2020. We searched Proquest Dissertations and Theses in November 2019. We reviewed reference lists of included trials and handsearched three international nutrition journals. We contacted authors of included trials to identify further potentially relevant trials. SELECTION CRITERIA: We included randomised controlled trials, including cluster-randomised controlled trials and cross-over trials, of any intervention primarily targeting consumption of fruit, vegetables or both among children aged five years and under, and incorporating a dietary or biochemical assessment of fruit or vegetable consumption. Two review authors independently screened titles and abstracts of identified papers; a third review author resolved disagreements. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risks of bias of included trials; a third review author resolved disagreements. Due to unexplained heterogeneity, we used random-effects models in meta-analyses for the primary review outcomes where we identified sufficient trials. We calculated standardised mean differences (SMDs) to account for the heterogeneity of fruit and vegetable consumption measures. We conducted assessments of risks of bias and evaluated the quality of evidence (GRADE approach) using Cochrane procedures. MAIN RESULTS: We included 80 trials with 218 trial arms and 12,965 participants. Fifty trials examined the impact of child-feeding practices (e.g. repeated food exposure) in increasing child vegetable intake. Fifteen trials examined the impact of parent nutrition education only in increasing child fruit and vegetable intake. Fourteen trials examined the impact of multicomponent interventions (e.g. parent nutrition education and preschool policy changes) in increasing child fruit and vegetable intake. Two trials examined the effect of a nutrition education intervention delivered to children in increasing child fruit and vegetable intake. One trial examined the impact of a child-focused mindfulness intervention in increasing vegetable intake. We judged 23 of the 80 included trials as free from high risks of bias across all domains. Performance, detection and attrition bias were the most common domains judged at high risk of bias for the remaining trials. There is low-quality evidence that child-feeding practices versus no intervention may have a small positive effect on child vegetable consumption, equivalent to an increase of 5.30 grams as-desired consumption of vegetables (SMD 0.50, 95% CI 0.29 to 0.71; 19 trials, 2140 participants; mean post-intervention follow-up = 8.3 weeks). Multicomponent interventions versus no intervention has a small effect on child consumption of fruit and vegetables (SMD 0.32, 95% CI 0.09 to 0.55; 9 trials, 2961 participants; moderate-quality evidence; mean post-intervention follow-up = 5.4 weeks), equivalent to an increase of 0.34 cups of fruit and vegetables a day. It is uncertain whether there are any short-term differences in child consumption of fruit and vegetables in meta-analyses of trials examining parent nutrition education versus no intervention (SMD 0.13, 95% CI -0.02 to 0.28; 11 trials, 3050 participants; very low-quality evidence; mean post-intervention follow-up = 13.2 weeks). We were unable to pool child nutrition education interventions in meta-analysis; both trials reported a positive intervention effect on child consumption of fruit and vegetables (low-quality evidence). Very few trials reported long-term effectiveness (6 trials), cost effectiveness (1 trial) or unintended adverse consequences of interventions (2 trials), limiting our ability to assess these outcomes. Trials reported receiving governmental or charitable funds, except for four trials reporting industry funding. AUTHORS' CONCLUSIONS: Despite identifying 80 eligible trials of various intervention approaches, the evidence for how to increase children's fruit and vegetable consumption remains limited in terms of quality of evidence and magnitude of effect. Of the types of interventions identified, there was moderate-quality evidence that multicomponent interventions probably lead to, and low-quality evidence that child-feeding practice may lead to, only small increases in fruit and vegetable consumption in children aged five years and under. It is uncertain whether parent nutrition education or child nutrition education interventions alone are effective in increasing fruit and vegetable consumption in children aged five years and under. Our confidence in effect estimates for all intervention approaches, with the exception of multicomponent interventions, is limited on the basis of the very low to low-quality evidence. Long-term follow-up of at least 12 months is required and future research should adopt more rigorous methods to advance the field. This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.


Assuntos
Fenômenos Fisiológicos da Nutrição Infantil , Frutas , Pais , Verduras , Pré-Escolar , Condicionamento Psicológico , Dieta , Comportamento Alimentar , Educação em Saúde , Humanos , Lactente , Pais/educação , Pais/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto
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