RESUMO
Energy balance is orchestrated by an extended network of highly interconnected nuclei across the central nervous system. While much is known about the hypothalamic circuits regulating energy homeostasis, the 'extra-hypothalamic' circuits involved are relatively poorly understood. In this review, we focus on the brainstem's dorsal raphe nucleus (DRN), integrating decades of research linking this structure to the physiologic and behavioral responses that maintain proper energy stores. DRN neurons sense and respond to interoceptive and exteroceptive cues related to energy imbalance and in turn induce appropriate alterations in energy intake and expenditure. The DRN is also molecularly differentiable, with different populations playing distinct and often opposing roles in controlling energy balance. These populations are integrated into the extended circuit known to regulate energy balance. Overall, this review summarizes the key evidence demonstrating an important role for the DRN in regulating energy balance.
Assuntos
Núcleo Dorsal da Rafe , Metabolismo Energético , Metabolismo Energético/fisiologia , Humanos , Hipotálamo/fisiologia , Neurônios/fisiologiaRESUMO
Translational profiling methodologies enable the systematic characterization of cell types in complex tissues, such as the mammalian brain, where neuronal isolation is exceptionally difficult. Here, we report a versatile strategy for profiling CNS cell types in a spatiotemporally restricted fashion by engineering a Cre-dependent adeno-associated virus expressing an EGFP-tagged ribosomal protein (AAV-FLEX-EGFPL10a) to access translating mRNAs by translating ribosome affinity purification (TRAP). We demonstrate the utility of this AAV to target a variety of genetically and anatomically defined neural populations expressing Cre recombinase and illustrate the ability of this viral TRAP (vTRAP) approach to recapitulate the molecular profiles obtained by bacTRAP in corticothalamic neurons across multiple serotypes. Furthermore, spatially restricting adeno-associated virus (AAV) injections enabled the elucidation of regional differences in gene expression within this cell type. Altogether, these results establish the broad applicability of the vTRAP strategy for the molecular dissection of any CNS or peripheral cell type that can be engineered to express Cre.