RESUMO
Significant evidence supports the view that dopamine shapes learning by encoding reward prediction errors. However, it is unknown whether striatal targets receive tailored dopamine dynamics based on regional functional specialization. Here, we report wave-like spatiotemporal activity patterns in dopamine axons and release across the dorsal striatum. These waves switch between activational motifs and organize dopamine transients into localized clusters within functionally related striatal subregions. Notably, wave trajectories were tailored to task demands, propagating from dorsomedial to dorsolateral striatum when rewards are contingent on animal behavior and in the opponent direction when rewards are independent of behavioral responses. We propose a computational architecture in which striatal dopamine waves are sculpted by inference about agency and provide a mechanism to direct credit assignment to specialized striatal subregions. Supporting model predictions, dorsomedial dopamine activity during reward-pursuit signaled the extent of instrumental control and interacted with reward waves to predict future behavioral adjustments.
Assuntos
Axônios/metabolismo , Comportamento Animal , Corpo Estriado/metabolismo , Dopamina/metabolismo , Recompensa , Animais , Feminino , Masculino , Camundongos , Camundongos MutantesRESUMO
Change history: In this Article, an extraneous label appeared in Fig. 4b, and has been removed in the online version.
RESUMO
The dopamine projection from ventral tegmental area (VTA) to nucleus accumbens (NAc) is critical for motivation to work for rewards and reward-driven learning. How dopamine supports both functions is unclear. Dopamine cell spiking can encode prediction errors, which are vital learning signals in computational theories of adaptive behaviour. By contrast, dopamine release ramps up as animals approach rewards, mirroring reward expectation. This mismatch might reflect differences in behavioural tasks, slower changes in dopamine cell spiking or spike-independent modulation of dopamine release. Here we compare spiking of identified VTA dopamine cells with NAc dopamine release in the same decision-making task. Cues that indicate an upcoming reward increased both spiking and release. However, NAc core dopamine release also covaried with dynamically evolving reward expectations, without corresponding changes in VTA dopamine cell spiking. Our results suggest a fundamental difference in how dopamine release is regulated to achieve distinct functions: broadcast burst signals promote learning, whereas local control drives motivation.
Assuntos
Dopamina/metabolismo , Aprendizagem/fisiologia , Motivação/fisiologia , Recompensa , Animais , Sinais (Psicologia) , Tomada de Decisões/fisiologia , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/metabolismo , Masculino , Núcleo Accumbens/citologia , Núcleo Accumbens/fisiologia , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/fisiologia , Ratos , Ratos Long-Evans , Fatores de Tempo , Área Tegmentar Ventral/citologia , Área Tegmentar Ventral/fisiologiaRESUMO
The prairie vole is a socially monogamous rodent that is an excellent animal model for studies of the neurobiology of social attachment. Such studies have demonstrated that activation of reward circuitry during social interactions facilitates pair bond formation. Within this circuitry, µ-opioid receptors (MORs) modulate naturally rewarding behavior in an anatomically segregated manner; MORs located throughout the striatum (dorsal striatum, NAc core, and the entire NAc shell) are implicated in general motivational processes, whereas those located specifically within the dorsomedial NAc shell mediate positive hedonics (and are referred to as a "hedonic hotspot"). The purpose of the present study was to determine whether MORs within these distinct subregions differentially mediate pair bond formation. We first used receptor autoradiography to compare MOR binding densities between these regions. MOR binding was significantly higher in the NAc core and dorsomedial NAc shell compared with the ventral NAc shell. We next used partner preference testing to determine whether MORs within these subregions differentially mediate pair bonding. Blockade of MORs using 1 or 3 µg of H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 within the dorsal striatum decreased mating during the cohabitation period and inhibited partner preference formation. In contrast, blockade of MORs within dorsomedial NAc shell inhibited partner preference formation without effecting mating behavior, whereas other regions were not involved. Thus, MORs within the dorsal striatum mediate partner preference formation via impairment of mating, whereas those in the dorsomedial NAc shell appear to mediate pair bond formation through the positive hedonics associated with mating.
Assuntos
Corpo Estriado/fisiologia , Ligação do Par , Receptores Opioides mu/metabolismo , Recompensa , Animais , Arvicolinae , Corpo Estriado/anatomia & histologia , Corpo Estriado/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Antagonistas de Entorpecentes/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/fisiologia , Peptídeos/farmacologia , Ligação Proteica/efeitos dos fármacosRESUMO
Throughout the educational system, students experiencing active learning pedagogy perform better and fail less than those taught through direct instruction. Can this be ascribed to differences in learning from a neuroscientific perspective? This review examines mechanistic, neuroscientific evidence that might explain differences in cognitive engagement contributing to learning outcomes between these instructional approaches. In classrooms, direct instruction comprehensively describes academic content, while active learning provides structured opportunities for learners to explore, apply, and manipulate content. Synaptic plasticity and its modulation by arousal or novelty are central to all learning and both approaches. As a form of social learning, direct instruction relies upon working memory. The reinforcement learning circuit, associated agency, curiosity, and peer-to-peer social interactions combine to enhance motivation, improve retention, and build higher-order-thinking skills in active learning environments. When working memory becomes overwhelmed, additionally engaging the reinforcement learning circuit improves retention, providing an explanation for the benefits of active learning. This analysis provides a mechanistic examination of how emerging neuroscience principles might inform pedagogical choices at all educational levels.
Assuntos
Neurociências , Humanos , Neurociências/educação , Aprendizagem Baseada em Problemas , Memória de Curto Prazo/fisiologia , Plasticidade Neuronal/fisiologia , Aprendizagem/fisiologia , Encéfalo/fisiologiaRESUMO
Etiopathogenic models for psychosis spectrum illnesses are converging on a number of key processes, such as the influence of specific genes on the synthesis of proteins important in synaptic functioning, alterations in how neurons respond to synaptic inputs and engage in synaptic pruning, and microcircuit dysfunction that leads to more global cortical information processing vulnerabilities. Disruptions in prefrontal operations then accumulate and propagate over time, interacting with environmental factors, developmental processes, and homeostatic mechanisms, eventually resulting in symptoms of psychosis and disability. However, there are 4 key features of psychosis spectrum illnesses that are of primary clinical relevance but have been difficult to assimilate into a single model and have thus far received little direct attention: 1) the bidirectionality of the causal influences for the emergence of psychosis, 2) the catastrophic clinical threshold seen in first episodes of psychosis and why it is irreversible in some individuals, 3) observed biotypes that are neurophysiologically distinct but clinically both convergent and divergent, and 4) a reconciliation of the role of striatal dopaminergic dysfunction with models of prefrontal cortical state instability. In this selective review, we briefly describe these 4 hallmark features and we argue that theoretically driven computational perspectives making use of both algorithmic and neurophysiologic models are needed to reduce this complexity and variability of psychosis spectrum illnesses in a principled manner.
Assuntos
Transtornos Psicóticos , Corpo Estriado/metabolismo , Dopamina , Humanos , Plasticidade Neuronal , Córtex Pré-Frontal/metabolismoRESUMO
Dopamine cell firing can encode errors in reward prediction, providing a learning signal to guide future behavior. Yet dopamine is also a key modulator of motivation, invigorating current behavior. Existing theories propose that fast (phasic) dopamine fluctuations support learning, whereas much slower (tonic) dopamine changes are involved in motivation. We examined dopamine release in the nucleus accumbens across multiple time scales, using complementary microdialysis and voltammetric methods during adaptive decision-making. We found that minute-by-minute dopamine levels covaried with reward rate and motivational vigor. Second-by-second dopamine release encoded an estimate of temporally discounted future reward (a value function). Changing dopamine immediately altered willingness to work and reinforced preceding action choices by encoding temporal-difference reward prediction errors. Our results indicate that dopamine conveys a single, rapidly evolving decision variable, the available reward for investment of effort, which is employed for both learning and motivational functions.