Cajal revisited: does the VMH make us fat?
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ABSTRACT: Melanocortin signaling plays a central role in the regulation of phenotypes related to body weight and energy homeostasis. To specifically target and study the function of proopiomelanocortin (POMC) neurons, Pomc promoter elements have been utilized to generate reporter and Cre recombinase transgenic reagents. Across gestation, we find that Pomc is dynamically expressed in many sites in the developing mouse forebrain, midbrain, hindbrain, spinal cord, and retina. Although Pomc expression in most embryonic brain regions is transient, it is sufficient to direct Cre-mediated recombination of floxed alleles. We visualize the populations affected by this transgene by crossing Pomc-Cre mice to ROSA reporter strains and identify 62 sites of recombination throughout the adult brain, including several nuclei implicated in energy homeostasis regulation. To compare the relationship between acute Pomc promoter activity and Pomc-Cre-mediated recombination at the single cell level, we crossed Pomc-enhanced green fluorescent protein (eGFP) and Pomc-Cre;ROSA-tdTomato lines. We detect the highest concentration of Pomc-eGFP+ cells in the arcuate nucleus of the hypothalamus and dentate gyrus but also observe smaller populations of labeled cells in the nucleus of the solitary tract, periventricular zone of the third ventricle, and cerebellum. Consistent with the dynamic nature of Pomc expression in the embryo, the vast majority of neurons marked with the tdTomato reporter do not express eGFP in the adult. Thus, recombination in off-target sites could contribute to physiological phenotypes using Pomc-Cre transgenics. For example, we find that approximately 83% of the cells in the arcuate nucleus of the hypothalamus immunoreactive for leptin-induced phosphorylated signal transducer and activator of transcription 3 are marked with Pomc-Cre;ROSA-tdTomato; only 13% of these are eGFP+ POMC neurons.Endocrinology 12/2011; 153(3):1219-31. DOI:10.1210/en.2011-1665 · 4.64 Impact Factor
- Nature medicine 04/2012; 18(4):496-7. DOI:10.1038/nm.2716 · 28.05 Impact Factor
Article: The many paths to fear.[Show abstract] [Hide abstract]
ABSTRACT: Fear is an emotion that has powerful effects on behaviour and physiology across animal species. It is accepted that the amygdala has a central role in processing fear. However, it is less widely appreciated that distinct amygdala outputs and downstream circuits are involved in different types of fear. Data show that fear of painful stimuli, predators and aggressive members of the same species are processed in independent neural circuits that involve the amygdala and downstream hypothalamic and brainstem circuits. Here, we discuss data supporting multiple fear pathways and the implications of this distributed system for understanding and treating fear.Nature Reviews Neuroscience 08/2012; 13(9):651-8. DOI:10.1038/nrn3301 · 31.38 Impact Factor