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1.
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
2.
Nat Commun ; 11(1): 4217, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868778

RESUMO

The cerebellum plays a crucial role in sensorimotor and associative learning. However, the contribution of molecular layer interneurons (MLIs) to these processes is not well understood. We used two-photon microscopy to study the role of ensembles of cerebellar MLIs in a go-no go task where mice obtain a sugar water reward if they lick a spout in the presence of the rewarded odorant and avoid a timeout when they refrain from licking for the unrewarded odorant. In naive animals the MLI responses did not differ between the odorants. With learning, the rewarded odorant elicited a large increase in MLI calcium responses, and the identity of the odorant could be decoded from the differential response. Importantly, MLIs switched odorant responses when the valence of the stimuli was reversed. Finally, mice took a longer time to refrain from licking in the presence of the unrewarded odorant and had difficulty becoming proficient when MLIs were inhibited by chemogenetic intervention. Our findings support a role for MLIs in learning valence in the cerebellum.


Assuntos
Cerebelo/fisiologia , Condicionamento Operante/fisiologia , Interneurônios/fisiologia , Aprendizagem/fisiologia , Células de Purkinje/fisiologia , Algoritmos , Animais , Cerebelo/citologia , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Fluorescência por Excitação Multifotônica , Modelos Neurológicos , Odorantes , Recompensa , Fatores de Tempo
3.
PLoS Comput Biol ; 16(9): e1008163, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32898146

RESUMO

Learning to avoid harmful consequences can be a costly trial-and-error process. In such situations, social information can be leveraged to improve individual learning outcomes. Here, we investigated how participants used their own experiences and others' social cues to avoid harm. Participants made repeated choices between harmful and safe options, each with different probabilities of generating shocks, while also seeing the image of a social partner. Some partners made predictive gaze cues towards the harmful choice option while others cued an option at random, and did so using neutral or fearful facial expressions. We tested how learned social information about partner reliability transferred across contexts by letting participants encounter the same partner in multiple trial blocks while facing novel choice options. Participants' decisions were best explained by a reinforcement learning model that independently learned the probabilities of options being safe and of partners being reliable and combined these combined these estimates to generate choices. Advice from partners making a fearful facial expression influenced participants' decisions more than advice from partners with neutral expressions. Our results showed that participants made better decisions when facing predictive partners and that they cached and transferred partner reliability estimates into new blocks. Using simulations we show that participants' transfer of social information into novel contexts is better adapted to variable social environments where social partners may change their cuing strategy or become untrustworthy. Finally, we found no relation between autism questionnaire scores and performance in our task, but do find autism trait related differences in learning rate parameters.


Assuntos
Aprendizagem da Esquiva/fisiologia , Condicionamento Operante/fisiologia , Comportamento Social , Comportamento de Escolha/fisiologia , Comunicação , Biologia Computacional , Sinais (Psicologia) , Fixação Ocular/fisiologia , Humanos
4.
Nat Hum Behav ; 4(10): 1067-1079, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32747804

RESUMO

The valence of new information influences learning rates in humans: good news tends to receive more weight than bad news. We investigated this learning bias in four experiments, by systematically manipulating the source of required action (free versus forced choices), outcome contingencies (low versus high reward) and motor requirements (go versus no-go choices). Analysis of model-estimated learning rates showed that the confirmation bias in learning rates was specific to free choices, but was independent of outcome contingencies. The bias was also unaffected by the motor requirements, thus suggesting that it operates in the representational space of decisions, rather than motoric actions. Finally, model simulations revealed that learning rates estimated from the choice-confirmation model had the effect of maximizing performance across low- and high-reward environments. We therefore suggest that choice-confirmation bias may be adaptive for efficient learning of action-outcome contingencies, above and beyond fostering person-level dispositions such as self-esteem.


Assuntos
Antecipação Psicológica/fisiologia , Comportamento de Escolha/fisiologia , Aprendizagem por Probabilidade , Desempenho Psicomotor/fisiologia , Recompensa , Adulto , Condicionamento Operante/fisiologia , Feminino , Humanos , Controle Interno-Externo , Masculino , Modelos Psicológicos , Modelos Estatísticos , Adulto Jovem
5.
Exp Psychol ; 67(2): 99-111, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32729400

RESUMO

Instrumental learning is regulated by two memory systems: a relatively rigid but efficient habit system and a flexible but resource-demanding goal-directed system. Previous work has demonstrated that exposure to acute stress may shift the balance between these systems toward the habitual system. In the current study, we used a 2-day outcome devaluation paradigm with a 75% reward contingency rate and altered food reward categories to replicate and extend our previous findings. Participants learned neutral stimulus-response-reward associations on the first day. On the second day, rewards were devalued by eating to satiety. Subsequently, acute stress was induced in half of the participants using the Maastricht Acute Stress Test, while the other half engaged in a nonstressful control task. Finally, relative goal-directed versus habitual behavior was evaluated in a slips-of-action phase, where more slips-of-action indicate a shift toward the habitual system. Results showed that participants successfully acquired the stimulus-response-reward associations, that devaluation was effective, and that stressed participants displayed significant increases in cortisol and blood pressure. Stress led participants to commit more slips-of-action compared with nonstressed controls. The current study extends previous work, showing that the employed paradigm and outcome devaluation procedure are boundary conditions to the stress-induced shift in instrumental responding.


Assuntos
Condicionamento Operante/fisiologia , Objetivos , Estresse Psicológico/psicologia , Adolescente , Adulto , Feminino , Hábitos , Humanos , Masculino , Adulto Jovem
6.
Nat Neurosci ; 23(8): 968-980, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32541962

RESUMO

The ventral tegmental area (VTA) is important for reward processing and motivation. The anatomic organization of neurotransmitter-specific inputs to the VTA remains poorly resolved. In the present study, we mapped the major neurotransmitter projections to the VTA through cell-type-specific retrograde and anterograde tracing. We found that glutamatergic inputs arose from a variety of sources and displayed some connectivity biases toward specific VTA cell types. The sources of GABAergic projections were more widespread, displayed a high degree of differential innervation of subregions in the VTA and were largely biased toward synaptic contact with local GABA neurons. Inactivation of GABA release from the two major sources, locally derived versus distally derived, revealed distinct roles for these projections in behavioral regulation. Optogenetic manipulation of individual distal GABAergic inputs also revealed differential behavioral effects. These results demonstrate that GABAergic projections to the VTA are a major contributor to the regulation and diversification of the structure.


Assuntos
Neurônios GABAérgicos/metabolismo , Transmissão Sináptica/fisiologia , Área Tegmentar Ventral/metabolismo , Animais , Condicionamento Clássico/fisiologia , Condicionamento Operante/fisiologia , Neurônios Dopaminérgicos/fisiologia , Medo/fisiologia , Feminino , Masculino , Camundongos , Atividade Motora/fisiologia , Vias Neurais/metabolismo , Optogenética , Recompensa , Autoestimulação
7.
Psychopharmacology (Berl) ; 237(8): 2395-2404, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32448943

RESUMO

RATIONALE: Menthol is a widely used tobacco constituent that has shown to enhance nicotine's reinforcing effects. OBJECTIVE: To determine whether injected menthol also alters nicotine's stimulus effects, we used a drug discrimination task. METHODS: A total of 57 adult Sprague-Dawley rats (28M, 29F) received 20 positive and 20 negative days (intermixed) of discrimination training. On positive days, rats received a group-specific menthol and nicotine injection (VEH + 0.1 NIC, 1 M + 0.1 NIC, 5 M + 0.1 NIC, VEH + 0.4 NIC, 1 M + 0.4 NIC, 5 M + 0.4 NIC; mg/kg) before eight 15-s cue light presentations (conditioned stimulus (CS)), each followed by 4-s sucrose access. On negative days, all rats were injected with vehicle and saline before eight non-reinforced CS presentations. Next, rats underwent generalization testing with 30 dose combinations of menthol and nicotine. The change in drug-mediated anticipatory goal tracking during the CS was calculated as a difference score (CS minus pre-CS responding). RESULTS: All groups readily acquired drug discrimination. However, difference scores for the 5M + 0.1 NIC group were lower for females. Additionally, females had lower scores for 0.05, 0.1, and 0.4 mg/kg nicotine generalization tests. The lowest nicotine dose discriminable from saline was 0.05 mg/kg for females but 0.025 mg/kg for males. Co-administration with 5 or 10 mg/kg menthol weakened discrimination performance between 0.1 and 0.4 mg/kg and between 0.1 and 0.05 mg/kg nicotine for 0.1 mg/kg nicotine training groups. CONCLUSIONS: Female rats that were trained with 0.1 mg/kg nicotine were more sensitive to menthol's modulatory effects on nicotine's stimulus effects. This highlights the importance of taking sex and training dose into account when evaluating the interoceptive stimulus effects of nicotine and menthol.


Assuntos
Aprendizagem por Discriminação/efeitos dos fármacos , Mentol/administração & dosagem , Nicotina/administração & dosagem , Reforço Psicológico , Caracteres Sexuais , Animais , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Aprendizagem por Discriminação/fisiologia , Relação Dose-Resposta a Droga , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Sacarose/administração & dosagem
8.
J Neurosci ; 40(24): 4727-4738, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32354856

RESUMO

Decades of research have shown that the NAc is a critical region influencing addiction, mood, and food consumption through its effects on reinforcement learning, motivation, and hedonic experience. Pharmacological studies have demonstrated that inhibition of the NAc shell induces voracious feeding, leading to the hypothesis that the inhibitory projections that emerge from the NAc normally act to restrict feeding. While much of this work has focused on projections to the lateral hypothalamus, the role of NAc projections to the VTA in the control food intake has been largely unexplored. Using a retrograde viral labeling technique and real-time monitoring of neural activity with fiber photometry, we find that medial NAc shell projections to the VTA (mNAc→VTA) are inhibited during food-seeking and food consumption in male mice. We also demonstrate that this circuit bidirectionally controls feeding: optogenetic activation of NAc projections to the VTA inhibits food-seeking and food intake (in both sexes), while optogenetic inhibition of this circuit potentiates food-seeking behavior. Additionally, we show that activity of the NAc to VTA pathway is necessary for adaptive inhibition of food intake in response to external cues. These data provide new insight into NAc control over feeding in mice, and contribute to an emerging literature elucidating the role of inhibitory midbrain feedback within the mesolimbic circuit.SIGNIFICANCE STATEMENT The medial NAc has long been known to control consummatory behavior, with particular focus on accumbens projections to the lateral hypothalamus. Conversely, NAc projections to the VTA have mainly been studied in the context of drug reward. We show that NAc projections to the VTA bidirectionally control food intake, consistent with a permissive role in feeding. Additionally, we show that this circuit is normally inactivated during consumption and food-seeking. Together, these findings elucidate how mesolimbic circuits control food consumption.


Assuntos
Comportamento Consumatório/fisiologia , Ingestão de Alimentos/fisiologia , Núcleo Accumbens/fisiologia , Área Tegmentar Ventral/fisiologia , Animais , Condicionamento Operante/fisiologia , Masculino , Camundongos , Atividade Motora/fisiologia , Vias Neurais/fisiologia , Optogenética , Recompensa
9.
J Neurosci ; 40(24): 4773-4787, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32393535

RESUMO

Flexible initiation or suppression of actions to avoid aversive events is crucial for survival. The prelimbic (PL) and infralimbic (IL) regions of the medial prefrontal cortex (mPFC) have been implicated in different aspects of avoidance and reward-seeking, but their respective contribution in instigating versus suppressing actions in aversive contexts remains to be clarified. We examined mPFC involvement in different forms of avoidance in rats well trained on different cued lever-press avoidance tasks. Active/inhibitory avoidance required flexible discrimination between auditory cues signaling foot-shock could be avoided by making or withholding instrumental responses. On a simpler active avoidance task, a single cue signaled when a lever press would avoid shock. PL inactivation disrupted active but not inhibitory avoidance on the discriminative task while having no effect on single-cued avoidance. In comparison, IL inactivation broadly impaired active and inhibitory avoidance. Conversely, on a cued appetitive go/no-go task, both IL and PL inactivation impaired inhibitory but not active reward-seeking, the latter effect being diametrically opposite to that observed on the avoidance task. These findings highlight the complex manner in which different mPFC regions aid in initiating or inhibiting actions in the service of avoiding aversive outcomes or obtaining rewarding ones. IL facilitates active avoidance but suppress inappropriate actions in appetitive and aversive contexts. In contrast, contextual valence plays a critical role in how the PL is recruited in initiating or suppressing actions, which may relate to the degree of cognitive control required to flexibly negotiate response or motivational conflicts and override prepotent behaviors.SIGNIFICANCE STATEMENT Choosing to make or withhold actions in a context-appropriate manner to avoid aversive events or obtain other goals is a critical survival skill. Different medial prefrontal cortex (mPFC) regions have been implicated in certain aspects of avoidance, but their contributions to instigating or suppressing actions remains to be clarified. Here, we show that the dorsal, prelimbic (PL) region of the medial PFC aids active avoidance in situations requiring flexible mitigation of response conflicts, but also aids in withholding responses to obtain rewards. In comparison the ventral infralimbic (IL) cortex plays a broader role in active and inhibitory avoidance as well as suppressing actions to obtain rewards. These findings provide insight into mechanisms underlying normal and maladaptive avoidance behaviors and response inhibition.


Assuntos
Aprendizagem da Esquiva/fisiologia , Cognição/fisiologia , Córtex Pré-Frontal/fisiologia , Recompensa , Animais , Condicionamento Operante/fisiologia , Sinais (Psicologia) , Extinção Psicológica/fisiologia , Masculino , Ratos , Ratos Long-Evans
10.
Neuron ; 106(5): 855-869.e8, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32240599

RESUMO

Predictive learning exerts a powerful influence over choice between instrumental actions. Nevertheless, how this learning is encoded in a sufficiently stable manner to influence choices that can occur much later in time is unclear. Here, we report that the basolateral amygdala (BLA) encodes predictive learning and establishes the memory necessary for future choices by driving the accumulation of delta-opioid receptors (DOPRs) on the somatic membrane of cholinergic interneurons in the nucleus accumbens shell (NAc-S). We found that the BLA controls DOPR accumulation via its influence on substance P release in the NAc-S, and that although DOPR accumulation is not necessary for predictive learning per se, it is necessary for the influence of this learning on later choice between actions. This study uncovers, therefore, a novel GPCR-based form of memory that is established by predictive learning and is necessary for such learning to guide the selection and execution of specific actions.


Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Comportamento de Escolha/fisiologia , Neurônios Colinérgicos/metabolismo , Interneurônios/metabolismo , Memória/fisiologia , Núcleo Accumbens/metabolismo , Receptores Opioides delta/metabolismo , Substância P/metabolismo , Animais , Condicionamento Clássico/fisiologia , Condicionamento Operante/fisiologia , Aprendizagem/fisiologia , Camundongos , Receptores Acoplados a Proteínas-G/metabolismo , Estriado Ventral
11.
PLoS One ; 15(4): e0230810, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32251443

RESUMO

Cognitive abilities underpin many of the behavioural decisions of animals. However, we still have very little understanding of how and why cognitive abilities vary between individuals of the same species in wild populations. In this study, we assessed the associative learning abilities of wild chacma baboons (Papio ursinus) across two troops in Namibia with a simple operant conditioning task. We evaluated the ability of individuals to correctly associate a particular colour of corn kernels with a distasteful flavour through repeated presentations of two small piles of corn dyed different colours, one of which had been treated with a non-toxic bitter substance. We also assessed whether individual variation in learning ability was associated with particular phenotypic traits (sex, social rank and neophilia) and states (age and prior vigilance). We found no evidence of learning the association either within each trial or across trials, nor any variation based on individuals' phenotypes. This appeared to be due to a high tolerance for bitter foods leading to similar acceptance of both palatable and unpalatable kernels. Earlier avoidance of the bitter kernels during pilot trials suggests this higher tolerance may have been largely driven by a drought during the experiments. Overall, our findings highlight the potential influence of current environmental challenges associated with conducting cognitive tests of animals in the wild.


Assuntos
Condicionamento Operante/fisiologia , Papio/fisiologia , Animais , Cognição/fisiologia , Feminino , Masculino , Namíbia , Papio ursinus/fisiologia , Fenótipo
12.
J Exp Psychol Anim Learn Cogn ; 46(2): 101-106, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32212774

RESUMO

The midsession reversal task involves a simple simultaneous discrimination in which, each session, choice of 1 stimulus (S1) is correct for the first 40 trials of each session, and choice of the other stimulus (S2) is correct for the remaining 40 trials. After considerable training with this task, pigeons typically continue to choose S2 too early (making anticipatory errors) and continue choosing S1 for following the reversal (making perseverative errors). Errors can be reduced, however, by decreasing the probability of reinforcement for correct S2 choices or by increasing the response requirement for S2 choices. Increasing the number of S2 stimuli (over trials, 1 S2 stimulus on each trial), however, does not reduce errors. Instead, it results in an increase in anticipatory errors but no change in perseverative errors. In the present experiment, we increased the number of S1 stimuli (over trials, 1 S1 stimulus on each trial) and found an increase in the number of perseverative errors but no change in anticipatory errors. The results suggest that the pigeons acquire this task by learning which stimuli to avoid, rather than which stimuli to choose, although it is also possible that these effects result from attention drawn to the variable stimuli when they are incorrect. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Aprendizagem da Esquiva/fisiologia , Comportamento Animal/fisiologia , Columbidae/fisiologia , Desempenho Psicomotor/fisiologia , Reversão de Aprendizagem/fisiologia , Animais , Condicionamento Operante/fisiologia
13.
Nat Protoc ; 15(4): 1542-1559, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32203485

RESUMO

It is difficult to translate results from animal research on addiction to an understanding of the behavior of human drug users. Despite decades of basic research on neurobiological mechanisms of drug addiction, treatment options remain largely unchanged. A potential reason for this is that mechanistic studies using rodent models do not incorporate a critical facet of human addiction: volitional choices between drug use and non-drug social rewards (e.g., employment and family). Recently, we developed an operant model in which rats press a lever for rewarding social interaction with a peer and then choose between an addictive drug (heroin or methamphetamine) and social interaction. Using this model, we showed that rewarding social interaction suppresses drug self-administration, relapse to drug seeking, and brain responses to drug-associated cues. Here, we describe a protocol for operant social interaction using a discrete-trial choice between drugs and social interaction that causes voluntary abstinence from the drug and tests for incubation of drug craving (the time-dependent increase in drug seeking during abstinence). This protocol is flexible but generally requires 8-9 weeks for completion. We also provide a detailed description of the technical requirements and procedures for building the social self-administration and choice apparatus. Our protocol provides a reliable way to study the role of operant social reward in addiction and addiction vulnerability in the context of choices. We propose that this protocol can be used to study brain mechanisms of operant social reward and potentially impairments in social reward in animal models of psychiatric disorders and pain.


Assuntos
Comportamento de Escolha/fisiologia , Condicionamento Operante/fisiologia , Comportamento de Procura de Droga/fisiologia , Modelos Psicológicos , Autoadministração/métodos , Animais , Modelos Animais de Doenças , Feminino , Heroína/administração & dosagem , Masculino , Metanfetamina/administração & dosagem , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Remifentanil/administração & dosagem , Comportamento Social , Transtornos Relacionados ao Uso de Substâncias/psicologia
14.
Behav Processes ; 175: 104106, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32209336

RESUMO

Two experiments examined factors controlling human free-operant performance in relation to predictions based on the nature of bout-initiation and within-bout responding. Overall, responding was higher for a random ratio (RR) than a random interval (RI) schedule, with equal rates of reinforcement. Bout-initiation rates were not different across the two schedules, but within-bout rates were higher on the RR schedule. Response cost reduced overall rates of responding, but tended to suppress bout-initiation responding more than within-bout responding (Experiments 1 & 2). In contrast, reinforcement magnitude increased all forms of responding (Experiment 2). One explanation consistent with these effects is that bout-initiation responses are controlled by overall rates of reinforcement through their impact on the context (i.e. are stimulus-driven), but that within-bout responses are controlled by response reinforcement (i.e. are goal-directed). These current findings are discussed in the light of these theoretical suggestions.


Assuntos
Condicionamento Operante/fisiologia , Desempenho Psicomotor/fisiologia , Reforço Psicológico , Adulto , Humanos , Esquema de Reforço
15.
J Neurosci ; 40(11): 2259-2268, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32024780

RESUMO

Frequency discrimination learning is often accompanied by an expansion of the functional region corresponding to the target frequency within the auditory cortex. Although the perceptual significance of this plastic functional reorganization remains debated, greater cortical representation is generally thought to improve perception for a stimulus. Recently, the ability to expand functional representations through passive sound experience has been demonstrated in adult rats, suggesting that it may be possible to design passive sound exposures to enhance specific perceptual abilities in adulthood. To test this hypothesis, we exposed adult female Long-Evans rats to 2 weeks of moderate-intensity broadband white noise followed by 1 week of 7 kHz tone pips, a paradigm that results in the functional over-representation of 7 kHz within the adult tonotopic map. We then tested the ability of exposed rats to identify 7 kHz among distractor tones on an adaptive tone discrimination task. Contrary to our expectations, we found that map expansion impaired frequency discrimination and delayed perceptual learning. Rats exposed to noise followed by 15 kHz tone pips were not impaired at the same task. Exposed rats also exhibited changes in auditory cortical responses consistent with reduced discriminability of the exposure tone. Encouragingly, these deficits were completely recovered with training. Our results provide strong evidence that map expansion alone does not imply improved perception. Rather, plastic changes in frequency representation induced by bottom-up processes can worsen perceptual faculties, but because of the very nature of plasticity these changes are inherently reversible.SIGNIFICANCE STATEMENT The potent ability of our acoustic environment to shape cortical sensory representations throughout life has led to a growing interest in harnessing both passive sound experience and operant perceptual learning to enhance mature cortical function. We use sound exposure to induce targeted expansions in the adult rat tonotopic map and find that these bottom-up changes unexpectedly impair performance on an adaptive tone discrimination task. Encouragingly, however, we also show that training promotes the recovery of electrophysiological measures of reduced neural discriminability following sound exposure. These results provide support for future neuroplasticity-based treatments that take into account both the sensory statistics of our external environment and perceptual training strategies to improve learning and memory in the adult auditory system.


Assuntos
Estimulação Acústica/efeitos adversos , Córtex Auditivo/fisiologia , Transtornos da Percepção/etiologia , Nível de Discriminação Sonora/fisiologia , Animais , Mapeamento Encefálico/métodos , Condicionamento Operante/fisiologia , Feminino , Plasticidade Neuronal , Ruído , Transtornos da Percepção/fisiopatologia , Transtornos da Percepção/reabilitação , Ratos , Ratos Long-Evans , Recompensa
16.
Behav Processes ; 173: 104061, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32017964

RESUMO

Context can influence the number of responses elicited by a discrete, appetitive conditioned stimulus (CS) but can context control when a CS elicits a response? To test this fundamental question, we gave male, Long-Evans rats Pavlovian conditioning sessions in which the same auditory conditioned stimulus (CS, 30 s, 15 trials/session) was presented in 2 different physical contexts on alternating days, according to a within-subjects design. In one context, called the early context, alcohol (15 % ethanol, 0.2 ml/trial) was delivered from the onset of the 5th second until the termination of the 10th second of the 30 s CS. In the second late context, alcohol was delivered from the onset of the 25th second until the termination of the 30th second of the same CS. In a comparison of the last session of training, the probability of making a conditioned response during the first four seconds of the CS was significantly higher in the early context than in the late context. This result shows that context can signal when an unconditioned stimulus occurs in relation to a CS and highlights a role for context in controlling precisely timed alcohol-seeking responses.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Condicionamento Clássico/fisiologia , Condicionamento Operante/fisiologia , Comportamento de Procura de Droga/fisiologia , Animais , Etanol , Masculino , Ratos , Ratos Long-Evans
17.
Cell ; 180(3): 536-551.e17, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-31955849

RESUMO

Goal-directed behavior requires the interaction of multiple brain regions. How these regions and their interactions with brain-wide activity drive action selection is less understood. We have investigated this question by combining whole-brain volumetric calcium imaging using light-field microscopy and an operant-conditioning task in larval zebrafish. We find global, recurring dynamics of brain states to exhibit pre-motor bifurcations toward mutually exclusive decision outcomes. These dynamics arise from a distributed network displaying trial-by-trial functional connectivity changes, especially between cerebellum and habenula, which correlate with decision outcome. Within this network the cerebellum shows particularly strong and predictive pre-motor activity (>10 s before movement initiation), mainly within the granule cells. Turn directions are determined by the difference neuroactivity between the ipsilateral and contralateral hemispheres, while the rate of bi-hemispheric population ramping quantitatively predicts decision time on the trial-by-trial level. Our results highlight a cognitive role of the cerebellum and its importance in motor planning.


Assuntos
Cerebelo/fisiologia , Tomada de Decisões/fisiologia , Tempo de Reação/fisiologia , Peixe-Zebra/fisiologia , Animais , Comportamento Animal/fisiologia , Mapeamento Encefálico/métodos , Cérebro/fisiologia , Cognição/fisiologia , Condicionamento Operante/fisiologia , Objetivos , Habenula/fisiologia , Temperatura Alta , Larva/fisiologia , Atividade Motora/fisiologia , Movimento , Neurônios/fisiologia , Desempenho Psicomotor/fisiologia , Rombencéfalo/fisiologia
18.
Nat Neurosci ; 23(2): 176-178, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31959935

RESUMO

Reward-evoked dopamine transients are well established as prediction errors. However, the central tenet of temporal difference accounts-that similar transients evoked by reward-predictive cues also function as errors-remains untested. In the present communication we addressed this by showing that optogenetically shunting dopamine activity at the start of a reward-predicting cue prevents second-order conditioning without affecting blocking. These results indicate that cue-evoked transients function as temporal-difference prediction errors rather than reward predictions.


Assuntos
Aprendizagem por Associação/fisiologia , Encéfalo/fisiologia , Dopamina/metabolismo , Animais , Condicionamento Operante/fisiologia , Sinais (Psicologia) , Neurônios Dopaminérgicos/fisiologia , Ratos , Ratos Long-Evans , Ratos Transgênicos , Recompensa
19.
J Neurosci ; 40(8): 1732-1743, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31953370

RESUMO

Reward-associated stimuli can both evoke conditioned responses and acquire reinforcing properties in their own right, becoming avidly pursued. Such conditioned stimuli (CS) can guide reward-seeking behavior in adaptive (e.g., locating food) and maladaptive (e.g., binge eating) ways. The basolateral amygdala (BLA) regulates conditioned responses evoked by appetitive CS, but less is known about how the BLA contributes to the instrumental pursuit of CS. Here we studied the influence of BLA neuron activity on both behavioral effects. Water-restricted male rats learned to associate a light-tone cue (CS) with water delivery into a port. During these Pavlovian conditioning sessions, we paired CS presentations with photo-stimulation of channelrhodopsin-2 (ChR2)-expressing BLA neurons. BLA photo-stimulation potentiated CS-evoked port entries during conditioning, indicating enhanced conditioned approach and appetitive conditioning. Next, new rats received Pavlovian conditioning without photo-stimulation. These rats then received instrumental conditioning sessions where they could press an inactive lever or an active lever that produced CS presentation, without water delivery. Rats pressed more on the active versus inactive lever, and pairing CS presentation with BLA-ChR2 photo-stimulation intensified responding for the CS. This suggests that BLA-ChR2 photo-stimulation enhanced CS incentive value. In a separate experiment, rats did not reliably self-administer BLA-ChR2 stimulations, suggesting that BLA neurons do not carry a primary reward signal. Last, intra-BLA infusions of d-amphetamine also intensified lever-pressing for the CS. The findings suggest that BLA-mediated activity facilitates CS control over behavior by enhancing both appetitive Pavlovian conditioning and instrumental pursuit of CS.SIGNIFICANCE STATEMENT Cues paired with rewards can guide animals to valuable resources such as food. Cues can also promote dysfunctional reward-seeking behavior, as in overeating. Reward-paired cues influence reward seeking through two major mechanisms. First, reward-paired cues evoke conditioned anticipatory behaviors to prepare for impending rewards. Second, reward-paired cues are powerful motivators and they can evoke pursuit in their own right. Here we show that increasing neural activity in the basolateral amygdala enhances both conditioned anticipatory behaviors and pursuit of reward-paired cues. The basolateral amygdala therefore facilitates cue-induced control over behavior by both increasing anticipation of impending rewards and making reward cues more attractive.


Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Condicionamento Operante/fisiologia , Recompensa , Animais , Comportamento Animal/fisiologia , Condicionamento Clássico/fisiologia , Sinais (Psicologia) , Masculino , Optogenética , Ratos , Ratos Sprague-Dawley
20.
Psychopharmacology (Berl) ; 237(4): 1147-1160, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31915862

RESUMO

RATIONALE: Cocaine addiction is a chronic brain disease characterized by compulsive drug intake and dysregulation of brain reward systems. Few preclinical studies have modeled the natural longitudinal course of cocaine addiction. Extended access self-administration protocols are powerful tools for modeling the advanced stages of addiction; however, few studies have duration of drug access longer than 12 h/session, potentially limiting their construct validity. Identification of changes in cocaine intake patterns during the development of addictive-like states may allow better treatments for vulnerable subjects. The kappa opioid receptor (KOPr) system has been implicated in the neurobiological regulation of addictive states as well as mood and stress disorders, with selective KOPr antagonists proposed as possible pharmacotherapeutic agents. Chronic cocaine exposure increases the expression of KOPr and its endogenous agonists, the dynorphins, in several brain areas in rodents. OBJECTIVES: To examine the behavioral pattern of intake during chronic (14 days) 18 h intravenous cocaine self-administration (0.5 mg/kg/infusion) and the effect of a novel short-acting KOPr antagonist LY2444296 HCl (3 mg/kg) administered during sessions 8 to 14 of chronic 18 h/day cocaine self-administration and prior to a single re-exposure session after 2 cocaine-free withdrawal days. RESULTS: Both daily and hourly cocaine intake patterns changed over 14 days of 18 h self-administration. LY pretreatment affected the pattern of self-administration across the second week of extended access cocaine self-administration and prevented the increase in cocaine intake during re-exposure. CONCLUSIONS: Overall, the KOPr antagonist attenuated escalated cocaine consumption in a rat model of extended access cocaine self-administration.


Assuntos
Comportamento Aditivo/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Cocaína/administração & dosagem , Antagonistas de Entorpecentes/farmacologia , Receptores Opioides kappa/antagonistas & inibidores , Animais , Comportamento Aditivo/metabolismo , Encéfalo/metabolismo , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Inibidores da Captação de Dopamina/administração & dosagem , Masculino , Antagonistas de Entorpecentes/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptores Opioides kappa/metabolismo , Autoadministração , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/metabolismo
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