RESUMO
Food and water are rewarding in part because they satisfy our internal needs1,2. Dopaminergic neurons in the ventral tegmental area (VTA) are activated by gustatory rewards3-5, but how animals learn to associate these oral cues with the delayed physiological effects of ingestion is unknown. Here we show that individual dopaminergic neurons in the VTA respond to detection of nutrients or water at specific stages of ingestion. A major subset of dopaminergic neurons tracks changes in systemic hydration that occur tens of minutes after thirsty mice drink water, whereas different dopaminergic neurons respond to nutrients in the gastrointestinal tract. We show that information about fluid balance is transmitted to the VTA by a hypothalamic pathway and then re-routed to downstream circuits that track the oral, gastrointestinal and post-absorptive stages of ingestion. To investigate the function of these signals, we used a paradigm in which a fluid's oral and post-absorptive effects can be independently manipulated and temporally separated. We show that mice rapidly learn to prefer one fluid over another based solely on its rehydrating ability and that this post-ingestive learning is prevented if dopaminergic neurons in the VTA are selectively silenced after consumption. These findings reveal that the midbrain dopamine system contains subsystems that track different modalities and stages of ingestion, on timescales from seconds to tens of minutes, and that this information is used to drive learning about the consequences of ingestion.
Assuntos
Dopamina , Neurônios Dopaminérgicos , Hipotálamo , Vias Neurais , Nutrientes , Estado de Hidratação do Organismo , Área Tegmentar Ventral , Animais , Sinais (Psicologia) , Digestão , Dopamina/metabolismo , Neurônios Dopaminérgicos/fisiologia , Ingestão de Alimentos , Trato Gastrointestinal/metabolismo , Hipotálamo/citologia , Hipotálamo/fisiologia , Mesencéfalo/citologia , Mesencéfalo/fisiologia , Camundongos , Nutrientes/metabolismo , Estado de Hidratação do Organismo/efeitos dos fármacos , Recompensa , Fatores de Tempo , Área Tegmentar Ventral/citologia , Área Tegmentar Ventral/fisiologia , Água/metabolismo , Água/farmacologia , Equilíbrio HidroeletrolíticoRESUMO
The strength of cortical connectivity to the striatum influences the balance between behavioral variability and stability. Learning to consistently produce a skilled action requires plasticity in corticostriatal connectivity associated with repeated training of the action. However, it remains unknown whether such corticostriatal plasticity occurs during training itself or 'offline' during time away from training, such as sleep. Here, we monitor the corticostriatal network throughout long-term skill learning in rats and find that non-rapid-eye-movement (NREM) sleep is a relevant period for corticostriatal plasticity. We first show that the offline activation of striatal NMDA receptors is required for skill learning. We then show that corticostriatal functional connectivity increases offline, coupled to emerging consistent skilled movements, and coupled cross-area neural dynamics. We then identify NREM sleep spindles as uniquely poised to mediate corticostriatal plasticity, through interactions with slow oscillations. Our results provide evidence that sleep shapes cross-area coupling required for skill learning.