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1.
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
2.
J Vis Exp ; (167)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33491674

RESUMO

Fear- and anxiety-related behaviors significantly contribute to an organism's survival. However, exaggerated defensive responses to perceived threat are characteristic of various anxiety disorders, which are the most prevalent form of mental illness in the United States. Discovering the neurobiological mechanisms responsible for defensive behaviors will aid in the development of novel therapeutic interventions. Pavlovian fear conditioning is a widely used laboratory paradigm to study fear-related learning and memory. A major limitation of traditional Pavlovian fear conditioning paradigms is that freezing is the only defensive behavior monitored. We recently developed a modified Pavlovian fear conditioning paradigm that allows us to study both conditioned freezing and flight (also known as escape) behavior within individual subjects. This model employs higher intensity footshocks and a greater number of pairings between the conditioned stimulus and unconditioned stimulus. Additionally, this conditioned flight paradigm utilizes serial presentation of pure tone and white noise auditory stimuli as the conditioned stimulus. Following conditioning in this paradigm, mice exhibit freezing behavior in response to the tone stimulus, and flight responses during the white noise. This conditioning model can be applied to the study of rapid and flexible transitions between behavioral responses necessary for survival.


Assuntos
Comportamento Animal , Condicionamento Clássico/fisiologia , Reação de Fuga/fisiologia , Medo/fisiologia , Reação de Congelamento Cataléptica/fisiologia , Animais , Extinção Psicológica , Feminino , Congelamento , Masculino , Memória/fisiologia , Camundongos Endogâmicos C57BL , Gravação em Vídeo
4.
PLoS One ; 15(12): e0243434, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33338047

RESUMO

In recent years, several studies of human predictive learning demonstrated better learning about outcomes that have previously been experienced as consistently predictable compared to outcomes previously experienced as less predictable, namely the outcome predictability effect. As this effect may have wide-reaching implications for current theories of associative learning, the present study aimed to examine the generality of the effect with a human goal-tracking paradigm, employing three different designs to manipulate the predictability of outcomes in an initial training phase. In contrast to the previous studies, learning in a subsequent phase, when every outcome was equally predictable by novel cues, was not reliably affected by the outcomes' predictability in the first phase. This lack of an outcome predictability effect provides insights into the parameters of the effect and its underlying mechanisms.


Assuntos
Aprendizagem por Associação/fisiologia , Atenção/fisiologia , Condicionamento Clássico , Adulto , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Estudantes
5.
Nat Commun ; 11(1): 6407, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33335094

RESUMO

Endocannabinoids retrogradely regulate synaptic transmission and their abundance is controlled by the fine balance between endocannabinoid synthesis and degradation. While the common assumption is that "on-demand" release determines endocannabinoid signaling, their rapid degradation is expected to control the temporal profile of endocannabinoid action and may impact neuronal signaling. Here we show that memory formation through fear conditioning selectively accelerates the degradation of endocannabinoids in the cerebellum. Learning induced a lasting increase in GABA release and this was responsible for driving the change in endocannabinoid degradation. Conversely, Gq-DREADD activation of cerebellar Purkinje cells enhanced endocannabinoid signaling and impaired memory consolidation. Our findings identify a previously unappreciated reciprocal interaction between GABA and the endocannabinoid system in which GABA signaling accelerates endocannabinoid degradation, and triggers a form of learning-induced metaplasticity.


Assuntos
Endocanabinoides/metabolismo , Consolidação da Memória/fisiologia , Transmissão Sináptica/fisiologia , Animais , Cerebelo/metabolismo , Condicionamento Clássico , Medo , Masculino , Camundongos Endogâmicos C57BL , Monoacilglicerol Lipases/metabolismo , Células de Purkinje/metabolismo , Células de Renshaw/metabolismo , Ácido gama-Aminobutírico/metabolismo
6.
Acta Gastroenterol Belg ; 83(4): 527-531, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33321007

RESUMO

Objective: This study aimed to discuss the effects of appetite-conditioned reflex stimulation on the early enteral nutrition (EEN) tolerance, complications, and postoperative hospital stay in patients who underwent surgery. Methods: Seventy patients who underwent laparoscopic radical resection of colorectal cancer surgery in our hospital between February and December 2017 were randomly divided into a stimulated appetite group (experimental group, including visual stimulation, nasal stimulation, taste stimulation and hearing stimulation) and a control group (n = 35). Both groups received EEN. EEN tolerance, complications, and postoperative hospital stay were then compared between the groups. Results: Sixty-six patients, including 34 in the experimental group and 32 in the control group, completed the relevant experiment. The experimental group had significantly lower incidence rates of nausea, vomiting, bloating, use of prokinetic drugs, and gastric tube replacement (P < 0.05), and shorter tolerable regular eating time (5.0 ± 1.0 d vs 6.4 ± 1.9 d, P < 0.05) and postoperative hospital stay (7.0 ± 2.0 d vs 8.0 ± 1.8 d, P < 0.05) than the control group. No significant difference in complication rate was detected (P > 0.05). Conclusion: Appetite-conditioned reflex stimulation can improve EEN tolerance, decrease the risk of complications, and shorten ordinary diet recovery time and hospital stay.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Nutrição Enteral , Apetite , Condicionamento Clássico , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle
7.
Nat Commun ; 11(1): 5113, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037215

RESUMO

Striatal activity is dynamically modulated by acetylcholine and dopamine, both of which are essential for basal ganglia function. Synchronized pauses in the activity of striatal cholinergic interneurons (ChINs) are correlated with elevated activity of midbrain dopaminergic neurons, whereas synchronous firing of ChINs induces local release of dopamine. The mechanisms underlying ChIN synchronization and its interplay with dopamine release are not fully understood. Here we show that polysynaptic inhibition between ChINs is a robust network motif and instrumental in shaping the network activity of ChINs. Action potentials in ChINs evoke large inhibitory responses in multiple neighboring ChINs, strong enough to suppress their tonic activity. Using a combination of optogenetics and chemogenetics we show the involvement of striatal tyrosine hydroxylase-expressing interneurons in mediating this inhibition. Inhibition between ChINs is attenuated by dopaminergic midbrain afferents acting presynaptically on D2 receptors. Our results present a novel form of interaction between striatal dopamine and acetylcholine dynamics.


Assuntos
Neurônios Colinérgicos/metabolismo , Corpo Estriado/citologia , Interneurônios/metabolismo , Inibição Neural/fisiologia , Transmissão Sináptica/fisiologia , Acetilcolina/fisiologia , Animais , Condicionamento Clássico , Corpo Estriado/fisiologia , Dopamina , Feminino , Masculino , Mesencéfalo/citologia , Mesencéfalo/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Técnicas de Patch-Clamp , Receptores de Dopamina D2/metabolismo , Recompensa
8.
Nat Commun ; 11(1): 5207, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060630

RESUMO

Fear conditioning is a form of associative learning that is known to involve different brain areas, notably the amygdala, the prefrontal cortex and the periaqueductal grey (PAG). Here, we describe the functional role of pathways that link the cerebellum with the fear network. We found that the cerebellar fastigial nucleus (FN) sends glutamatergic projections to vlPAG that synapse onto glutamatergic and GABAergic vlPAG neurons. Chemogenetic and optogenetic manipulations revealed that the FN-vlPAG pathway controls bi-directionally the strength of the fear memories, indicating an important role in the association of the conditioned and unconditioned stimuli, a function consistent with vlPAG encoding of fear prediction error. Moreover, FN-vlPAG projections also modulate extinction learning. We also found a FN-parafascicular thalamus pathway, which may relay cerebellar influence to the amygdala and modulates anxiety behaviors. Overall, our results reveal multiple contributions of the cerebellum to the emotional system.


Assuntos
Sistema Nervoso Central/fisiologia , Medo/fisiologia , Memória/fisiologia , Vias Neurais/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Tonsila do Cerebelo/fisiologia , Animais , Sistema Nervoso Central/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/fisiologia , Condicionamento Clássico/fisiologia , Condicionamento Operante/fisiologia , Aprendizagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Optogenética
9.
Nat Commun ; 11(1): 4819, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968048

RESUMO

In many parts of the nervous system, experience-dependent refinement of neuronal circuits predominantly involves synapse elimination. The role of sleep in this process remains unknown. We investigated the role of sleep in experience-dependent dendritic spine elimination of layer 5 pyramidal neurons in the visual (V1) and frontal association cortex (FrA) of 1-month-old mice. We found that monocular deprivation (MD) or auditory-cued fear conditioning (FC) caused rapid spine elimination in V1 or FrA, respectively. MD- or FC-induced spine elimination was significantly reduced after total sleep or REM sleep deprivation. Total sleep or REM sleep deprivation also prevented MD- and FC-induced reduction of neuronal activity in response to visual or conditioned auditory stimuli. Furthermore, dendritic calcium spikes increased substantially during REM sleep, and the blockade of these calcium spikes prevented MD- and FC-induced spine elimination. These findings reveal an important role of REM sleep in experience-dependent synapse elimination and neuronal activity reduction.


Assuntos
Córtex Cerebral/fisiologia , Espinhas Dendríticas/fisiologia , Sono REM/fisiologia , Animais , Condicionamento Clássico , Medo/fisiologia , Camundongos , Camundongos Transgênicos , Modelos Animais , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Células Piramidais/fisiologia , Privação Sensorial/fisiologia , Privação do Sono , Sinapses , Córtex Visual/fisiologia
10.
Proc Natl Acad Sci U S A ; 117(40): 25116-25127, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32958652

RESUMO

The ventromedial prefrontal cortex (vmPFC) is a key brain structure implicated in mood and anxiety disorders, based primarily on evidence from correlational neuroimaging studies. Composed of a number of brain regions with distinct architecture and connectivity, dissecting its functional heterogeneity will provide key insights into the symptomatology of these disorders. Focusing on area 14, lying on the medial and orbital surfaces of the gyrus rectus, this study addresses a key question of causality. Do changes in area 14 activity induce changes in threat- and reward-elicited responses within the nonhuman primate, the common marmoset, similar to that seen in mood and anxiety disorders? Area 14 overactivation was found to induce heightened responsivity to uncertain, low-imminence threat while blunting cardiovascular and behavioral anticipatory arousal to high-value food reward. Conversely, inactivation enhanced the arousal to high-value reward cues while dampening the acquisition of cardiovascular and behavioral responses to a Pavlovian threat cue. Basal cardiovascular activity, including heart rate variability and sympathovagal balance, which are dysfunctional in mood and anxiety disorders, are insensitive to alterations in area 14 activity as is the extinction of conditioned threat responses. The distinct pattern of dysregulation compared to neighboring region area 25 highlights the heterogeneity of function within vmPFC and reveals how the effects of area 14 overactivation on positive and negative reactivity mirror symptoms of anhedonia and anxiety that are so often comorbid in mood disorders.


Assuntos
Ansiedade/diagnóstico por imagem , Mapeamento Encefálico , Callithrix/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Animais , Ansiedade/fisiopatologia , Condicionamento Clássico/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Imagem por Ressonância Magnética , Córtex Pré-Frontal/fisiologia , Recompensa
11.
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
12.
PLoS One ; 15(9): e0239270, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32936829

RESUMO

In a between-subject comparison of two memantine administration schedules we observed that treatment with the NMDA receptor antagonist memantine before testing sessions reduced ingestion of a 10% sucrose solution in rats, due to reduced licking burst size, thus suggesting a blunted hedonic response. Conversely, daily post-session administration reduced burst number, indicating a reduced level of behavioural activation, likely due to the development of conditioned taste aversion (CTA). In this study, the effect of pre-session and post-session memantine administration was investigated within-subjects. Memantine was administered in daily intraperitoneal injections for 13 days, on alternate days, either 1-h before-"before testing" sessions-or immediately after a 30-min session-"after testing" sessions. The effects on the microstructure of licking for a 10% sucrose solution were examined in the course of treatment and for 21 days after treatment discontinuation. The results show reduced burst size in the "before testing" sessions, without effects on the intra-burst lick rate, an index of motoric effects. Moreover, burst number was reduced since the third session of both administration conditions until the end of treatment. Interestingly, the effect of memantine of reducing the activation of ingestive behaviour was less pronounced in this study with respect to that observed with the previous study post-session administration schedule, in spite of the longer treatment. This apparent paradox might be explained if one considers these effects as instances of a memory-related effect, such as the development of CTA. In the framework of this hypothesis, the "before testing" sessions, not being followed by memantine administration, can be considered as extinction sessions performed every other day. Moreover, the animals treated with memantine at the highest dose failed to recover to pre-treatment ingestion levels 21 days after treatment discontinuation, while the animals treated after testing sessions in the previously published study showed a complete recovery well before the 15th day test. Within the same interpretative framework, this might depend by the reduced number and frequency of the extinction trials-i.e. the number of the sessions run after treatment discontinuation-in the present study. These results provide further support to the conclusion that memantine administration before sessions reduce burst size, an effect which is likely due to blockade of NMDA receptors occurring during behavioural testing. The observation that this effect can be obtained even in absence of a reduced intra-burst lick rate, which rules out the involvement of motor impairment, provides an important piece of evidence in support to the interpretation of this effect as a blunted hedonic response. Moreover, these results provide further evidence that burst number reduction is due to a memory-related effect induced by memantine administration after sessions.


Assuntos
Comportamento Alimentar/efeitos dos fármacos , Memantina/farmacologia , Memória/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Condicionamento Clássico/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Ingestão de Alimentos , Humanos , Memantina/efeitos adversos , Memória/fisiologia , Ratos , Receptores de N-Metil-D-Aspartato/genética
13.
Elife ; 92020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32909941

RESUMO

In 2016 we reported evidence for associative learning in plants (Gagliano et al., 2016). In view of the far-reaching implications of this finding we welcome the attempt made by Markel to replicate our study (Markel, 2020). However, as we discuss here, the protocol employed by Markel was unsuitable for testing for associative learning.


Assuntos
Condicionamento Clássico , Ervilhas
14.
Elife ; 92020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32909944

RESUMO

In 2016 Gagliano et al. reported evidence for associative learning in plants (Gagliano et al., 2016). A subsequent attempt to replicate this finding by the present author was not successful (Markel, 2020). Gagliano et al. attribute this lack of replication to differences in the experimental set-ups used in the original work and the replication attempt (Gagliano et al., 2020). Here, based on a comparison of the two set-ups, I argue that these differences are unable to explain the lack of replication in Markel, 2020.


Assuntos
Condicionamento Clássico , Ervilhas
15.
Nat Commun ; 11(1): 3845, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737295

RESUMO

Many experimental studies suggest that animals can rapidly learn to identify odors and predict the rewards associated with them. However, the underlying plasticity mechanism remains elusive. In particular, it is not clear how olfactory circuits achieve rapid, data efficient learning with local synaptic plasticity. Here, we formulate olfactory learning as a Bayesian optimization process, then map the learning rules into a computational model of the mammalian olfactory circuit. The model is capable of odor identification from a small number of observations, while reproducing cellular plasticity commonly observed during development. We extend the framework to reward-based learning, and show that the circuit is able to rapidly learn odor-reward association with a plausible neural architecture. These results deepen our theoretical understanding of unsupervised learning in the mammalian brain.


Assuntos
Condicionamento Clássico/fisiologia , Rede Nervosa , Plasticidade Neuronal/fisiologia , Condutos Olfatórios/fisiologia , Percepção Olfatória/fisiologia , Olfato/fisiologia , Animais , Teorema de Bayes , Simulação por Computador , Mamíferos , Neurônios/citologia , Neurônios/fisiologia , Odorantes/análise , Bulbo Olfatório/fisiologia , Recompensa
16.
Neuron ; 108(1): 209-224.e6, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-32827456

RESUMO

The representation of odor in olfactory cortex (piriform) is distributive and unstructured and can only be afforded behavioral significance upon learning. We performed 2-photon imaging to examine the representation of odors in piriform and in two downstream areas, the orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC), as mice learned olfactory associations. In piriform, we observed that odor responses were largely unchanged during learning. In OFC, 30% of the neurons acquired robust responses to conditioned stimuli (CS+) after learning, and these responses were gated by internal state and task context. Moreover, direct projections from piriform to OFC can be entrained to elicit learned olfactory behavior. CS+ responses in OFC diminished with continued training, whereas persistent representations of both CS+ and CS- odors emerged in mPFC. Optogenetic silencing indicates that these two brain structures function sequentially to consolidate the learning of appetitive associations.


Assuntos
Comportamento Apetitivo/fisiologia , Aprendizagem por Associação/fisiologia , Neurônios/fisiologia , Odorantes , Condutos Olfatórios/fisiologia , Córtex Piriforme/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Condicionamento Clássico/fisiologia , Microscopia Intravital , Camundongos , Microscopia de Fluorescência por Excitação Multifotônica , Optogenética , Córtex Piriforme/citologia , Córtex Pré-Frontal/citologia
17.
Nat Commun ; 11(1): 3764, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32724058

RESUMO

Context can influence reactions to environmental cues and this elemental process has implications for substance use disorder. Using an animal model, we show that an alcohol-associated context elevates entry into a fluid port triggered by a conditioned stimulus (CS) that predicted alcohol (CS-triggered alcohol-seeking). This effect persists across multiple sessions and, after it diminishes in extinction, the alcohol context retains the capacity to augment reinstatement. Systemically administered eticlopride and chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons reduce CS-triggered alcohol-seeking. Chemogenetically silencing VTA dopamine terminals in the nucleus accumbens (NAc) core reduces CS-triggered alcohol-seeking, irrespective of context, whereas silencing VTA dopamine terminals in the NAc shell selectively reduces the elevation of CS-triggered alcohol-seeking in an alcohol context. This dissociation reveals new roles for divergent mesolimbic dopamine circuits in the control of responding to a discrete cue for alcohol and in the amplification of this behaviour in an alcohol context.


Assuntos
Transtornos Relacionados ao Uso de Álcool/psicologia , Dopamina/metabolismo , Etanol/administração & dosagem , Extinção Psicológica/fisiologia , Área Tegmentar Ventral/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Sinais (Psicologia) , Modelos Animais de Doenças , Antagonistas de Dopamina/administração & dosagem , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Comportamento de Procura de Droga/efeitos dos fármacos , Comportamento de Procura de Droga/fisiologia , Extinção Psicológica/efeitos dos fármacos , Feminino , Humanos , Masculino , Ratos , Salicilamidas/administração & dosagem , Técnicas Estereotáxicas , Área Tegmentar Ventral/citologia
18.
Nervenarzt ; 91(8): 667-674, 2020 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-32642946

RESUMO

The learned placebo response of the immune system is based on the mutual interaction between the brain and the immune system; both systems continually exchange information via humoral and neural communication pathways. This communication network enables the modification, i.e. suppression or stimulation, of peripheral immune functions by classical or Pavlov's conditioning. The present article provides an overview of the results of recent experimental animal studies, which also document the potential clinical relevance of learned immune responses. Learned immunological responses mediated by classical conditioning have also been demonstrated in humans. The knowledge gained from experimental data and clinical observations paves the way for a potential implementation of learned immune responses as supportive measures to standard immunopharmacological treatment strategies to reduce drug dosage as well as adverse side effects while simultaneously maximizing the therapeutic effect.


Assuntos
Sistema Imunitário , Aprendizagem , Efeito Placebo , Animais , Encéfalo , Condicionamento Clássico , Humanos
19.
Proc Natl Acad Sci U S A ; 117(28): 16678-16689, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32601212

RESUMO

Physical proximity to a traumatic event increases the severity of accompanying stress symptoms, an effect that is reminiscent of evolutionarily configured fear responses based on threat imminence. Despite being widely adopted as a model system for stress and anxiety disorders, fear-conditioning research has not yet characterized how threat proximity impacts the mechanisms of fear acquisition and extinction in the human brain. We used three-dimensional (3D) virtual reality technology to manipulate the egocentric distance of conspecific threats while healthy adult participants navigated virtual worlds during functional magnetic resonance imaging (fMRI). Consistent with theoretical predictions, proximal threats enhanced fear acquisition by shifting conditioned learning from cognitive to reactive fear circuits in the brain and reducing amygdala-cortical connectivity during both fear acquisition and extinction. With an analysis of representational pattern similarity between the acquisition and extinction phases, we further demonstrate that proximal threats impaired extinction efficacy via persistent multivariate representations of conditioned learning in the cerebellum, which predicted susceptibility to later fear reinstatement. These results show that conditioned threats encountered in close proximity are more resistant to extinction learning and suggest that the canonical neural circuitry typically associated with fear learning requires additional consideration of a more reactive neural fear system to fully account for this effect.


Assuntos
Encéfalo/fisiologia , Condicionamento Clássico , Medo , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
20.
Nat Commun ; 11(1): 3318, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620879

RESUMO

Decision-making is guided by memories of option values. However, retrieving items from memory renders them malleable. Here, we show that merely retrieving values from memory and making a choice between options is sufficient both to induce changes to stimulus-reward associations in the hippocampus and to bias future decision-making. After allowing participants to make repeated choices between reward-conditioned stimuli, in the absence of any outcome, we observe that participants prefer stimuli they have previously chosen, and neglect previously unchosen stimuli, over otherwise identical-valued options. Using functional brain imaging, we show that decisions induce changes to hippocampal representations of stimulus-outcome associations. These changes are correlated with future decision biases. Our results indicate that choice-induced preference changes are partially driven by choice-induced modification of memory representations and suggest that merely making a choice - even without experiencing any outcomes - induces associative plasticity.


Assuntos
Comportamento de Escolha/fisiologia , Tomada de Decisões/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Adulto , Algoritmos , Viés , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Condicionamento Clássico/fisiologia , Hipocampo/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Desempenho Psicomotor/fisiologia , Recompensa , Adulto Jovem
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