RESUMO
Empirical evidence suggests that heat exposure reduces food intake. However, the neurocircuit architecture and the signalling mechanisms that form an associative interface between sensory and metabolic modalities remain unknown, despite primary thermoceptive neurons in the pontine parabrachial nucleus becoming well characterized1. Tanycytes are a specialized cell type along the wall of the third ventricle2 that bidirectionally transport hormones and signalling molecules between the brain's parenchyma and ventricular system3-8. Here we show that tanycytes are activated upon acute thermal challenge and are necessary to reduce food intake afterwards. Virus-mediated gene manipulation and circuit mapping showed that thermosensing glutamatergic neurons of the parabrachial nucleus innervate tanycytes either directly or through second-order hypothalamic neurons. Heat-dependent Fos expression in tanycytes suggested their ability to produce signalling molecules, including vascular endothelial growth factor A (VEGFA). Instead of discharging VEGFA into the cerebrospinal fluid for a systemic effect, VEGFA was released along the parenchymal processes of tanycytes in the arcuate nucleus. VEGFA then increased the spike threshold of Flt1-expressing dopamine and agouti-related peptide (Agrp)-containing neurons, thus priming net anorexigenic output. Indeed, both acute heat and the chemogenetic activation of glutamatergic parabrachial neurons at thermoneutrality reduced food intake for hours, in a manner that is sensitive to both Vegfa loss-of-function and blockage of vesicle-associated membrane protein 2 (VAMP2)-dependent exocytosis from tanycytes. Overall, we define a multimodal neurocircuit in which tanycytes link parabrachial sensory relay to the long-term enforcement of a metabolic code.
Assuntos
Tronco Encefálico , Células Ependimogliais , Comportamento Alimentar , Temperatura Alta , Hipotálamo , Vias Neurais , Neurônios , Animais , Feminino , Masculino , Camundongos , Proteína Relacionada com Agouti/metabolismo , Núcleo Arqueado do Hipotálamo/metabolismo , Núcleo Arqueado do Hipotálamo/citologia , Tronco Encefálico/citologia , Tronco Encefálico/fisiologia , Dopamina/metabolismo , Ingestão de Alimentos/fisiologia , Células Ependimogliais/citologia , Células Ependimogliais/fisiologia , Comportamento Alimentar/fisiologia , Ácido Glutâmico/metabolismo , Hipotálamo/citologia , Hipotálamo/fisiologia , Vias Neurais/metabolismo , Neurônios/metabolismo , Núcleos Parabraquiais/citologia , Núcleos Parabraquiais/metabolismo , Núcleos Parabraquiais/fisiologia , Sensação Térmica/fisiologia , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/líquido cefalorraquidiano , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The ability to care for the young is innate and readily displayed by postpartum females after delivery to ensure offspring survival. Upon pup exposure, rodent virgin (nulliparous) females also develop parental behavior that over time becomes displayed at levels equivalent to parenting mothers. Although maternal behavior in postpartum females and the associated neurocircuits are well characterized, the neural mechanisms underlying the acquisition of maternal behavior without prior experience remain poorly understood. Here, we show that the development of maternal care behavior in response to first-time pup exposure in virgin females is initiated by the activation of the anterior cingulate cortex (ACC). ACC activity is dependent on feedback excitation by Vglut2+ /Galanin+ neurons of the centrolateral nucleus of the thalamus (CL), with their activity sufficient to display parenting behaviors. Accordingly, acute bidirectional chemogenetic manipulation of neuronal activity in the ACC facilitates or impairs the attainment of maternal behavior, exclusively in virgin females. These results reveal an ACC-CL neurocircuit as an accessory loop in virgin females for the initiation of maternal care upon first-time exposure to pups.