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1.
Nat Commun ; 12(1): 1040, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589613

RESUMO

Animals exhibit innate defense behaviors in response to approaching threats cued by the dynamics of sensory inputs of various modalities. The underlying neural circuits have been mostly studied in the visual system, but remain unclear for other modalities. Here, by utilizing sounds with increasing (vs. decreasing) loudness to mimic looming (vs. receding) objects, we find that looming sounds elicit stereotypical sequential defensive reactions: freezing followed by flight. Both behaviors require the activity of auditory cortex, in particular the sustained type of responses, but are differentially mediated by corticostriatal projections primarily innervating D2 neurons in the tail of the striatum and corticocollicular projections to the superior colliculus, respectively. The behavioral transition from freezing to flight can be attributed to the differential temporal dynamics of the striatal and collicular neurons in their responses to looming sound stimuli. Our results reveal an essential role of the striatum in the innate defense control.


Assuntos
Córtex Auditivo/fisiologia , Corpo Estriado/fisiologia , Reação de Fuga/fisiologia , Reação de Congelamento Cataléptica/fisiologia , Instinto , Estimulação Acústica , Animais , Córtex Auditivo/anatomia & histologia , Percepção Auditiva/fisiologia , Corpo Estriado/anatomia & histologia , Sinais (Psicologia) , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/citologia , Neurônios/fisiologia , Som , Colículos Superiores/anatomia & histologia , Colículos Superiores/fisiologia
2.
Elife ; 92020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33345774

RESUMO

Different regions of the striatum regulate different types of behavior. However, how dopamine signals differ across striatal regions and how dopamine regulates different behaviors remain unclear. Here, we compared dopamine axon activity in the ventral, dorsomedial, and dorsolateral striatum, while mice performed a perceptual and value-based decision task. Surprisingly, dopamine axon activity was similar across all three areas. At a glance, the activity multiplexed different variables such as stimulus-associated values, confidence, and reward feedback at different phases of the task. Our modeling demonstrates, however, that these modulations can be inclusively explained by moment-by-moment changes in the expected reward, that is the temporal difference error. A major difference between areas was the overall activity level of reward responses: reward responses in dorsolateral striatum were positively shifted, lacking inhibitory responses to negative prediction errors. The differences in dopamine signals put specific constraints on the properties of behaviors controlled by dopamine in these regions.


Assuntos
Axônios/fisiologia , Corpo Estriado/fisiologia , Tomada de Decisões/fisiologia , Neurônios Dopaminérgicos/fisiologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Odorantes , Reforço Psicológico , Recompensa , Olfato
3.
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
4.
Nat Commun ; 11(1): 4669, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938940

RESUMO

The prefrontal cortex and striatum form a recurrent network whose spiking activity encodes multiple types of learning-relevant information. This spike-encoded information is evident in average firing rates, but finer temporal coding might allow multiplexing and enhanced readout across the connected network. We tested this hypothesis in the fronto-striatal network of nonhuman primates during reversal learning of feature values. We found that populations of neurons encoding choice outcomes, outcome prediction errors, and outcome history in their firing rates also carry significant information in their phase-of-firing at a 10-25 Hz band-limited beta frequency at which they synchronize across lateral prefrontal cortex, anterior cingulate cortex and anterior striatum when outcomes were processed. The phase-of-firing code exceeds information that can be obtained from firing rates alone and is evident for inter-areal connections between anterior cingulate cortex, lateral prefrontal cortex and anterior striatum. For the majority of connections, the phase-of-firing information gain is maximal at phases of the beta cycle that were offset from the preferred spiking phase of neurons. Taken together, these findings document enhanced information of three important learning variables at specific phases of firing in the beta cycle at an inter-areally shared beta oscillation frequency during goal-directed behavior.


Assuntos
Corpo Estriado/fisiologia , Giro do Cíngulo/fisiologia , Aprendizagem/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Análise por Conglomerados , Corpo Estriado/citologia , Sincronização de Fases em Eletroencefalografia , Eletrofisiologia/métodos , Eletrofisiologia/estatística & dados numéricos , Giro do Cíngulo/citologia , Macaca mulatta , Masculino , Rede Nervosa , Córtex Pré-Frontal/citologia , Recompensa
5.
PLoS Biol ; 18(8): e3000800, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776945

RESUMO

Studies of neural processes underlying delay of gratification usually focus on prefrontal networks related to curbing affective impulses. Here, we provide evidence for an alternative mechanism that facilitates delaying gratification by mental orientation towards the future. Combining continuous theta-burst stimulation (cTBS) with functional neuroimaging, we tested how the right temporoparietal junction (rTPJ) facilitates processing of future events and thereby promotes delay of gratification. Participants performed an intertemporal decision task and a mental time-travel task in the MRI scanner before and after receiving cTBS over the rTPJ or the vertex (control site). rTPJ cTBS led to both stronger temporal discounting for longer delays and reduced processing of future relative to past events in the mental time-travel task. This finding suggests that the rTPJ contributes to the ability to delay gratification by facilitating mental representation of outcomes in the future. On the neural level, rTPJ cTBS led to a reduction in the extent to which connectivity of rTPJ with striatum reflected the value of delayed rewards, indicating a role of rTPJ-striatum connectivity in constructing neural representations of future rewards. Together, our findings provide evidence that the rTPJ is an integral part of a brain network that promotes delay of gratification by facilitating mental orientation to future rewards.


Assuntos
Corpo Estriado/fisiologia , Tomada de Decisões/fisiologia , Desvalorização pelo Atraso/fisiologia , Rede Nervosa/fisiologia , Lobo Parietal/fisiologia , Lobo Temporal/fisiologia , Adulto , Mapeamento Encefálico , Corpo Estriado/anatomia & histologia , Corpo Estriado/diagnóstico por imagem , Feminino , Neuroimagem Funcional , Humanos , Comportamento Impulsivo/fisiologia , Masculino , Rede Nervosa/anatomia & histologia , Rede Nervosa/diagnóstico por imagem , Lobo Parietal/anatomia & histologia , Lobo Parietal/diagnóstico por imagem , Recompensa , Lobo Temporal/anatomia & histologia , Lobo Temporal/diagnóstico por imagem , Estimulação Magnética Transcraniana
6.
Proc Natl Acad Sci U S A ; 117(34): 20890-20897, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32817467

RESUMO

Multimodal evidence suggests that brain regions accumulate information over timescales that vary according to anatomical hierarchy. Thus, these experimentally defined "temporal receptive windows" are longest in cortical regions that are distant from sensory input. Interestingly, spontaneous activity in these regions also plays out over relatively slow timescales (i.e., exhibits slower temporal autocorrelation decay). These findings raise the possibility that hierarchical timescales represent an intrinsic organizing principle of brain function. Here, using resting-state functional MRI, we show that the timescale of ongoing dynamics follows hierarchical spatial gradients throughout human cerebral cortex. These intrinsic timescale gradients give rise to systematic frequency differences among large-scale cortical networks and predict individual-specific features of functional connectivity. Whole-brain coverage permitted us to further investigate the large-scale organization of subcortical dynamics. We show that cortical timescale gradients are topographically mirrored in striatum, thalamus, and cerebellum. Finally, timescales in the hippocampus followed a posterior-to-anterior gradient, corresponding to the longitudinal axis of increasing representational scale. Thus, hierarchical dynamics emerge as a global organizing principle of mammalian brains.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Vias Neurais/fisiologia , Adulto , Córtex Cerebral/fisiologia , Corpo Estriado/fisiologia , Bases de Dados Factuais , Feminino , Substância Cinzenta/fisiologia , Hipocampo/fisiologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Descanso/fisiologia , Fatores de Tempo
7.
PLoS Comput Biol ; 16(7): e1008078, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32701987

RESUMO

Animals remember temporal links between their actions and subsequent rewards. We previously discovered a synaptic mechanism underlying such reward learning in D1 receptor (D1R)-expressing spiny projection neurons (D1 SPN) of the striatum. Dopamine (DA) bursts promote dendritic spine enlargement in a time window of only a few seconds after paired pre- and post-synaptic spiking (pre-post pairing), which is termed as reinforcement plasticity (RP). The previous study has also identified underlying signaling pathways; however, it still remains unclear how the signaling dynamics results in RP. In the present study, we first developed a computational model of signaling dynamics of D1 SPNs. The D1 RP model successfully reproduced experimentally observed protein kinase A (PKA) activity, including its critical time window. In this model, adenylate cyclase type 1 (AC1) in the spines/thin dendrites played a pivotal role as a coincidence detector against pre-post pairing and DA burst. In particular, pre-post pairing (Ca2+ signal) stimulated AC1 with a delay, and the Ca2+-stimulated AC1 was activated by the DA burst for the asymmetric time window. Moreover, the smallness of the spines/thin dendrites is crucial to the short time window for the PKA activity. We then developed a RP model for D2 SPNs, which also predicted the critical time window for RP that depended on the timing of pre-post pairing and phasic DA dip. AC1 worked for the coincidence detector in the D2 RP model as well. We further simulated the signaling pathway leading to Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation and clarified the role of the downstream molecules of AC1 as the integrators that turn transient input signals into persistent spine enlargement. Finally, we discuss how such timing windows guide animals' reward learning.


Assuntos
Sinalização do Cálcio , Corpo Estriado/fisiologia , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Dopamina/fisiologia , Aprendizagem , Plasticidade Neuronal , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/fisiologia , Simulação por Computador , Dendritos/fisiologia , Espinhas Dendríticas/fisiologia , Cinética , Camundongos , Neurônios/fisiologia , Receptores de Dopamina D2 , Recompensa
8.
Proc Natl Acad Sci U S A ; 117(30): 18049-18058, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32661170

RESUMO

Cognitive flexibility depends on a fast neural learning mechanism for enhancing momentary relevant over irrelevant information. A possible neural mechanism realizing this enhancement uses fast spiking interneurons (FSIs) in the striatum to train striatal projection neurons to gate relevant and suppress distracting cortical inputs. We found support for such a mechanism in nonhuman primates during the flexible adjustment of visual attention in a reversal learning task. FSI activity was modulated by visual attention cues during feature-based learning. One FSI subpopulation showed stronger activation during learning, while another FSI subpopulation showed response suppression after learning, which could indicate a disinhibitory effect on the local circuit. Additionally, FSIs that showed response suppression to learned attention cues were activated by salient distractor events, suggesting they contribute to suppressing bottom-up distraction. These findings suggest that striatal fast spiking interneurons play an important role when cues are learned that redirect attention away from previously relevant to newly relevant visual information. This cue-specific activity was independent of motor-related activity and thus tracked specifically the learning of reward predictive visual features.


Assuntos
Atenção , Corpo Estriado/fisiologia , Sinais (Psicologia) , Interneurônios/fisiologia , Aprendizagem , Vias Neurais , Primatas , Potenciais de Ação , Animais , Cognição
9.
PLoS One ; 15(5): e0226790, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32365120

RESUMO

Patients with DYT1 dystonia caused by the mutated TOR1A gene exhibit risk neutral behaviour compared to controls who are risk averse in the same reinforcement learning task. It is unclear whether this behaviour can be linked to changes in cortico-striatal plasticity demonstrated in animal models which share the same TOR1A mutation. We hypothesised that we could reproduce the experimental risk taking behaviour using a model of the basal ganglia under conditions where cortico-striatal plasticity was abnormal. As dopamine exerts opposing effects on cortico-striatal plasticity via different receptors expressed on medium spiny neurons (MSN) of the direct (D1R dominant, dMSNs) and indirect (D2R dominant, iMSNs) pathways, we tested whether abnormalities in cortico-striatal plasticity in one or both of these pathways could explain the patient's behaviour. Our model could generate simulated behaviour indistinguishable from patients when cortico-striatal plasticity was abnormal in both dMSNs and iMSNs in opposite directions. The risk neutral behaviour of the patients was replicated when increased cortico-striatal long term potentiation in dMSN's was in combination with increased long term depression in iMSN's. This result is consistent with previous observations in rodent models of increased cortico-striatal plasticity at in dMSNs, but contrasts with the pattern reported in vitro of dopamine D2 receptor dependant increases in cortico-striatal LTP and loss of LTD at iMSNs. These results suggest that additional factors in patients who manifest motor symptoms may lead to divergent effects on D2 receptor dependant cortico-striatal plasticity that are not apparent in rodent models of this disease.


Assuntos
Dopamina/genética , Distonia Muscular Deformante/genética , Chaperonas Moleculares/genética , Receptores de Dopamina D2/genética , Animais , Gânglios da Base/metabolismo , Gânglios da Base/fisiologia , Comportamento Animal/fisiologia , Ciências Biocomportamentais , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Dopamina/metabolismo , Distonia Muscular Deformante/psicologia , Feminino , Humanos , Aprendizagem/fisiologia , Potenciação de Longa Duração/genética , Potenciação de Longa Duração/fisiologia , Masculino , Rigidez Muscular/genética , Rigidez Muscular/patologia , Mutação/genética , Vias Neurais/metabolismo , Plasticidade Neuronal/genética , Plasticidade Neuronal/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Reforço Psicológico , Assunção de Riscos , Roedores/genética , Roedores/fisiologia , Sinapses/genética
10.
Nat Neurosci ; 23(7): 800-804, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32424287

RESUMO

Experiential diversity promotes well-being in animal models. Here, using geolocation tracking, experience sampling and neuroimaging, we found that daily variability in physical location was associated with increased positive affect in humans. This effect was stronger for individuals who exhibited greater functional coupling of the hippocampus and striatum. These results link diversity in real-world daily experiences to fluctuations in positive affect and identify a hippocampal-striatal circuit associated with this bidirectional relationship.


Assuntos
Afeto/fisiologia , Corpo Estriado/fisiologia , Comportamento Exploratório/fisiologia , Hipocampo/fisiologia , Vias Neurais/fisiologia , Adolescente , Adulto , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
11.
Nat Commun ; 11(1): 2555, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444624

RESUMO

Fetal alcohol exposure (FAE) is the leading preventable developmental cause of cognitive dysfunction. Even in the absence of binge drinking, alcohol consumption during pregnancy can leave offspring deficient. However, the mechanisms underlying these deficiencies are unknown. Using a mouse model of gestational ethanol exposure (GEE), we show increased instrumental lever-pressing and disruption of efficient habitual actions in adults, indicative of disrupted cognitive function. In vivo electrophysiology reveals disrupted action encoding in dorsolateral striatum (DLS) associated with altered habit learning. GEE mice exhibit decreased GABAergic transmission onto DLS projection neurons, including inputs from parvalbumin interneurons, and increased endocannabinoid tone. Chemogenetic activation of DLS parvalbumin interneurons reduces the elevated lever pressing of GEE mice. Pharmacologically increasing endocannabinoid tone mimics GEE effects on cognition and synaptic transmission. These findings show GEE induces long-lasting deficits in cognitive function that may contribute to human FAE, and identify potential mechanisms for future therapeutic targeting.


Assuntos
Corpo Estriado/fisiopatologia , Etanol/efeitos adversos , Exposição Materna/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/psicologia , Animais , Cognição/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Etanol/metabolismo , Feminino , Desenvolvimento Fetal , Humanos , Masculino , Camundongos Endogâmicos C57BL , Linhagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia
12.
Proc Natl Acad Sci U S A ; 117(17): 9554-9565, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32321828

RESUMO

The basal ganglia play an important role in decision making and selection of action primarily based on input from cortex, thalamus, and the dopamine system. Their main input structure, striatum, is central to this process. It consists of two types of projection neurons, together representing 95% of the neurons, and 5% of interneurons, among which are the cholinergic, fast-spiking, and low threshold-spiking subtypes. The membrane properties, soma-dendritic shape, and intrastriatal and extrastriatal synaptic interactions of these neurons are quite well described in the mouse, and therefore they can be simulated in sufficient detail to capture their intrinsic properties, as well as the connectivity. We focus on simulation at the striatal cellular/microcircuit level, in which the molecular/subcellular and systems levels meet. We present a nearly full-scale model of the mouse striatum using available data on synaptic connectivity, cellular morphology, and electrophysiological properties to create a microcircuit mimicking the real network. A striatal volume is populated with reconstructed neuronal morphologies with appropriate cell densities, and then we connect neurons together based on appositions between neurites as possible synapses and constrain them further with available connectivity data. Moreover, we simulate a subset of the striatum involving 10,000 neurons, with input from cortex, thalamus, and the dopamine system, as a proof of principle. Simulation at this biological scale should serve as an invaluable tool to understand the mode of operation of this complex structure. This platform will be updated with new data and expanded to simulate the entire striatum.


Assuntos
Simulação por Computador , Corpo Estriado/fisiologia , Fenômenos Eletrofisiológicos , Modelos Biológicos , Neurônios/fisiologia , Animais , Córtex Cerebral/fisiologia , Corpo Estriado/citologia , Dopamina/metabolismo , Camundongos , Receptores Dopaminérgicos/metabolismo , Tálamo/fisiologia
13.
Nat Commun ; 11(1): 1957, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32327644

RESUMO

Action control is a key brain function determining the survival of animals in their environment. In mammals, neurons expressing dopamine D2 receptors (D2R) in the dorsal striatum (DS) and the nucleus accumbens (Acb) jointly but differentially contribute to the fine regulation of movement. However, their region-specific molecular features are presently unknown. By combining RNAseq of striatal D2R neurons and histological analyses, we identified hundreds of novel region-specific molecular markers, which may serve as tools to target selective subpopulations. As a proof of concept, we characterized the molecular identity of a subcircuit defined by WFS1 neurons and evaluated multiple behavioral tasks after its temporally-controlled deletion of D2R. Consequently, conditional D2R knockout mice displayed a significant reduction in digging behavior and an exacerbated hyperlocomotor response to amphetamine. Thus, targeted molecular analyses reveal an unforeseen heterogeneity in D2R-expressing striatal neuronal populations, underlying specific D2R's functional features in the control of specific motor behaviors.


Assuntos
Neostriado/citologia , Neurônios/fisiologia , Núcleo Accumbens/citologia , Receptores de Dopamina D2/metabolismo , Anfetamina/farmacologia , Animais , Biomarcadores/metabolismo , Corpo Estriado/citologia , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Dopaminérgicos/farmacologia , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Atividade Motora/efeitos dos fármacos , Atividade Motora/genética , Neostriado/metabolismo , Neostriado/fisiologia , Vias Neurais , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , Núcleo Accumbens/fisiologia , Receptores de Dopamina D2/genética
14.
PLoS Comput Biol ; 16(4): e1007648, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32302302

RESUMO

Medium spiny neurons (MSNs) comprise over 90% of cells in the striatum. In vivo MSNs display coherent burst firing cell assembly activity patterns, even though isolated MSNs do not burst fire intrinsically. This activity is important for the learning and execution of action sequences and is characteristically dysregulated in Huntington's Disease (HD). However, how dysregulation is caused by the various neural pathologies affecting MSNs in HD is unknown. Previous modeling work using simple cell models has shown that cell assembly activity patterns can emerge as a result of MSN inhibitory network interactions. Here, by directly estimating MSN network model parameters from single unit spiking data, we show that a network composed of much more physiologically detailed MSNs provides an excellent quantitative fit to wild type (WT) mouse spiking data, but only when network parameters are appropriate for the striatum. We find the WT MSN network is situated in a regime close to a transition from stable to strongly fluctuating network dynamics. This regime facilitates the generation of low-dimensional slowly varying coherent activity patterns and confers high sensitivity to variations in cortical driving. By re-estimating the model on HD spiking data we discover network parameter modifications are consistent across three very different types of HD mutant mouse models (YAC128, Q175, R6/2). In striking agreement with the known pathophysiology we find feedforward excitatory drive is reduced in HD compared to WT mice, while recurrent inhibition also shows phenotype dependency. We show that these modifications shift the HD MSN network to a sub-optimal regime where higher dimensional incoherent rapidly fluctuating activity predominates. Our results provide insight into a diverse range of experimental findings in HD, including cognitive and motor symptoms, and may suggest new avenues for treatment.


Assuntos
Corpo Estriado/fisiologia , Doença de Huntington/fisiopatologia , Animais , Mapeamento Encefálico , Modelos Animais de Doenças , Progressão da Doença , Neurônios GABAérgicos/metabolismo , Homozigoto , Humanos , Proteína Huntingtina/metabolismo , Camundongos , Camundongos Transgênicos , Mutação , Neurônios/fisiologia , Fenótipo , Radiocirurgia
15.
Nat Hum Behav ; 4(5): 531-543, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32231281

RESUMO

Curiosity is often portrayed as a desirable feature of human faculty. However, curiosity may come at a cost that sometimes puts people in harmful situations. Here, using a set of behavioural and neuroimaging experiments with stimuli that strongly trigger curiosity (for example, magic tricks), we examine the psychological and neural mechanisms underlying the motivational effect of curiosity. We consistently demonstrate that across different samples, people are indeed willing to gamble, subjecting themselves to electric shocks to satisfy their curiosity for trivial knowledge that carries no apparent instrumental value. Also, this influence of curiosity shares common neural mechanisms with that of hunger for food. In particular, we show that acceptance (compared to rejection) of curiosity-driven or incentive-driven gambles is accompanied by enhanced activity in the ventral striatum when curiosity or hunger was elicited, which extends into the dorsal striatum when participants made a decision.


Assuntos
Corpo Estriado/fisiologia , Tomada de Decisões/fisiologia , Comportamento Exploratório , Fome/fisiologia , Estriado Ventral/diagnóstico por imagem , Estriado Ventral/fisiologia , Corpo Estriado/diagnóstico por imagem , Eletrochoque/psicologia , Comportamento Exploratório/fisiologia , Feminino , Jogo de Azar/diagnóstico por imagem , Jogo de Azar/fisiopatologia , Humanos , Magia/psicologia , Imagem por Ressonância Magnética , Masculino , Motivação/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Neuroimagem , Núcleo Accumbens/diagnóstico por imagem , Núcleo Accumbens/fisiologia , Adulto Jovem
16.
Sci Rep ; 10(1): 4949, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188908

RESUMO

Deficits in instrumental, goal-directed control, combined with the influence of drug-associated Pavlovian-conditioned stimuli, are thought to influence the development and maintenance of addiction. However, direct evidence has mainly come from animal studies. We sought to establish whether alcohol use disorder (AUD) is characterized by behavioral or neurobiological deficits in (i) the integration of Pavlovian and instrumental values and (ii) goal-directed control; and (iii) whether duration or severity of AUD is associated with such deficits. The influence of cues predicting food rewards on instrumental action was assessed in a Pavlovian-to-instrumental transfer (PIT) test, measuring both specific and general PIT, and goal-directed behavior in an outcome-devaluation test. Brain activity was measured using functional MRI in 38 abstinent individuals with AUD and 22 matched healthy control individuals (HCs). We found significant specific and general PIT and outcome-devaluation effects across groups indicating goal-directed control, mediated by distinct corticostriatal signals, but no significant differences between individuals with AUD and healthy controls. Bayesian analyses provided substantial-to-strong evidence for the absence of group differences for these effects, or any relationship with duration or severity of AUD. These results suggest intact ability to integrate action-outcome associations on specific and general PIT and goal-directed learning in AUD during abstinence.


Assuntos
Alcoolismo/fisiopatologia , Córtex Cerebral/fisiologia , Corpo Estriado/fisiologia , Vias Neurais/fisiologia , Reforço Psicológico , Transferência de Experiência , Adulto , Estudos de Casos e Controles , Condicionamento Clássico , Condicionamento Operante , Sinais (Psicologia) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Science ; 367(6477): 549-555, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-32001651

RESUMO

Extinction learning allows animals to withhold voluntary actions that are no longer related to reward and so provides a major source of behavioral control. Although such learning is thought to depend on dopamine signals in the striatum, the way the circuits that mediate goal-directed control are reorganized during new learning remains unknown. Here, by mapping a dopamine-dependent transcriptional activation marker in large ensembles of spiny projection neurons (SPNs) expressing dopamine receptor type 1 (D1-SPNs) or 2 (D2-SPNs) in mice, we demonstrate an extensive and dynamic D2- to D1-SPN transmodulation across the striatum that is necessary for updating previous goal-directed learning. Our findings suggest that D2-SPNs suppress the influence of outdated D1-SPN plasticity within functionally relevant striatal territories to reshape volitional action.


Assuntos
Corpo Estriado/fisiologia , Neurônios Dopaminérgicos/fisiologia , Objetivos , Aprendizagem/fisiologia , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Animais , Corpo Estriado/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nucleossomos/metabolismo , Racloprida/farmacologia , Receptores de Dopamina D1/antagonistas & inibidores
18.
PLoS Comput Biol ; 16(2): e1007300, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32097404

RESUMO

Striatal oscillatory activity is associated with movement, reward, and decision-making, and observed in several interacting frequency bands. Local field potential recordings in rodent striatum show dopamine- and reward-dependent transitions between two states: a "spontaneous" state involving ß (∼15-30 Hz) and low γ (∼40-60 Hz), and a state involving θ (∼4-8 Hz) and high γ (∼60-100 Hz) in response to dopaminergic agonism and reward. The mechanisms underlying these rhythmic dynamics, their interactions, and their functional consequences are not well understood. In this paper, we propose a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of these rhythms, as well as their modulation by dopamine. Building on previous modeling and experimental work suggesting that striatal projection neurons (SPNs) are capable of generating ß oscillations, we show that networks of striatal fast-spiking interneurons (FSIs) are capable of generating δ/θ (ie, 2 to 6 Hz) and γ rhythms. Under simulated low dopaminergic tone our model FSI network produces low γ band oscillations, while under high dopaminergic tone the FSI network produces high γ band activity nested within a δ/θ oscillation. SPN networks produce ß rhythms in both conditions, but under high dopaminergic tone, this ß oscillation is interrupted by δ/θ-periodic bursts of γ-frequency FSI inhibition. Thus, in the high dopamine state, packets of FSI γ and SPN ß alternate at a δ/θ timescale. In addition to a mechanistic explanation for previously observed rhythmic interactions and transitions, our model suggests a hypothesis as to how the relationship between dopamine and rhythmicity impacts motor function. We hypothesize that high dopamine-induced periodic FSI γ-rhythmic inhibition enables switching between ß-rhythmic SPN cell assemblies representing the currently active motor program, and thus that dopamine facilitates movement in part by allowing for rapid, periodic shifts in motor program execution.


Assuntos
Ondas Encefálicas , Corpo Estriado/fisiologia , Potenciais de Ação/fisiologia , Animais , Biofísica , Dopamina/fisiologia , Modelos Neurológicos
19.
J Neurosci ; 40(10): 2139-2153, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-31969469

RESUMO

Despite clear evidence linking the basal ganglia to the control of outcome insensitivity (i.e., habit) and behavioral vigor (i.e., its behavioral speed/fluidity), it remains unclear whether or how these functions relate to one another. Here, using male Long-Evans rats in response-based and cue-based maze-running tasks, we demonstrate that phasic dorsolateral striatum (DLS) activity occurring at the onset of a learned behavior regulates how vigorous and habitual it is. In a response-based task, brief optogenetic excitation at the onset of runs decreased run duration and the occurrence of deliberative behaviors, whereas midrun stimulation carried little effect. Outcome devaluation showed these runs to be habitual. DLS inhibition at run start did not produce robust effects on behavior until after outcome devaluation. At that time, when the DLS was plausibly most critically required for performance (i.e., habitual), inhibition reduced performance vigor measures and caused a dramatic loss of habitual responding (i.e., animals quit the task). In a second cue-based "beacon" task requiring behavior initiation at the start of the run and again in the middle of the run, DLS excitation at both time points could improve the vigor of runs. Postdevaluation testing showed behavior on the beacon task to be habitual as well. This pattern of results suggests that one role for phasic DLS activity at behavior initiation is to promote the execution of the behavior in a vigorous and habitual fashion by a diverse set of measures.SIGNIFICANCE STATEMENT Our research expands the literature twofold. First, we find that features of a habitual behavior that are typically studied separately (i.e., maze response performance, deliberation movements, running vigor, and outcome insensitivity) are quite closely linked together. Second, efforts have been made to understand "what" the dorsolateral striatum (DLS) does for habitual behavior, and our research provides a key set of results showing "when" it is important (i.e., at behavior initiation). By showing such dramatic control over habits by DLS activity in a phasic time window, plausible real-world applications could involve more informed DLS perturbations to curb intractably problematic habits.


Assuntos
Comportamento Animal/fisiologia , Corpo Estriado/fisiologia , Hábitos , Animais , Masculino , Ratos , Ratos Long-Evans
20.
J Neurosci ; 40(8): 1679-1688, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31953369

RESUMO

The striatum is critical for controlling motor output. However, it remains unclear how striatal output neurons encode and facilitate movement. A prominent theory suggests that striatal units encode movements in bursts of activity near specific events, such as the start or end of actions. These bursts are theorized to gate or permit specific motor actions, thereby encoding and facilitating complex sequences of actions. An alternative theory has suggested that striatal neurons encode continuous changes in sensory or motor information with graded changes in firing rate. Supporting this theory, many striatal neurons exhibit such graded changes without bursting near specific actions. Here, we evaluated these two theories in the same recordings of mice (both male and female). We recorded single-unit and multiunit activity from the dorsomedial striatum of mice as they spontaneously explored an arena. We observed both types of encoding, although continuous encoding was more prevalent than bursting near movement initiation or termination. The majority of recorded units did not exhibit positive linear relationships with speed but instead exhibited nonlinear relationships that peaked at a range of locomotor speeds. Bulk calcium recordings of identified direct and indirect pathway neurons revealed similar speed tuning profiles, indicating that the heterogeneity in response profiles was not due to this genetic distinction. We conclude that continuous encoding of speed is a central component of movement encoding in the striatum.SIGNIFICANCE STATEMENT The striatum is a structure that is linked to volitional movements and is a primary site of pathology in movement disorders. It remains unclear how striatal neurons encode motor parameters and use them to facilitate movement. Here, we evaluated two models for this: a "discrete encoding model" in which striatal neurons facilitate movements with brief burst of activity near the start and end of movements, and a "continuous encoding model," in which striatal neurons encode the sensory or motor state of the animal with continuous changes in firing. We found evidence primarily in support of the continuous encoding model. This may have implications for understanding the striatal control of movement, as well as informing therapeutic approaches for treating movement disorders.


Assuntos
Corpo Estriado/fisiologia , Comportamento Exploratório/fisiologia , Movimento/fisiologia , Neurônios/fisiologia , Potenciais de Ação/fisiologia , Animais , Feminino , Masculino , Camundongos
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