title: MEMRI detects neuronal activity and connectivity in hypothalamic neural circuit responding to leptin.
abstract: Hypothalamus plays the central role in regulating energy homeostasis. To understand the hypothalamic neurocircuit in responding to leptin, Manganese-Enhanced MRI (MEMRI) was applied. Highly elevated signal could be mapped in major nuclei of the leptin signaling pathway, including the arcuate nucleus (ARC), paraventricular nucleus (PVN), ventromedial hypothalamus (VMH) and dorsomedial hypothalamus (DMH) in fasted mice and the enhancement was reduced by leptin administration. However, whether changes in MEMRI signal reflect Ca2+channel activity, neuronal activation or connectivity in the leptin signaling pathway are not clear. By blocking L-type Ca2+channels, the signal enhancement in the ARC, PVN and DMH, but not VMH, was reduced. By disrupting microtubule with colchicine, signal enhancement of the secondary neural areas like DMH and PVN was delayed which is consistent with the known projection density from ARC into these regions. Finally, strong correlation between c-fos expression and MEMRI signal increase rate was observed in the ARC, VMH and DMH. Together, we provide experimental evidence that MEMRI signal could represent activity and connectivity in certain hypothalamic nuclei and hence may be used for mapping activated neuronal pathway in vivo. This understanding would facilitate the application of MEMRI for evaluation of hypothalamic dysfunction in metabolic diseases.
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A⁎STAR), Singapore; Department of Physiology, National University of Singapore, Singapore.
authors.forename: Anna
authors.initials: A
authors.lastname: Ulyanova
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A⁎STAR), Singapore.
authors.forename: Xuan Vinh
authors.initials: XV
authors.lastname: To
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A⁎STAR), Singapore.
authors.forename: A B M A
authors.initials: ABMA
authors.lastname: Asad
authors.affiliation: Lab of Metabolic Medicine, Singapore Bioimaging Consortium, A⁎STAR, Singapore.
authors.forename: Weiping
authors.initials: W
authors.lastname: Han
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A⁎STAR), Singapore; Department of Physiology, National University of Singapore, Singapore. Electronic address: kaichuang@gmail.com.
authors.forename: Kai-Hsiang
authors.initials: KH
authors.lastname: Chuang
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000000981:diagnostic imaging* / Q000378:metabolism; D004302:Dorsomedial Hypothalamic Nucleus / Q000000981:diagnostic imaging* / Q000378:metabolism; D007089:Image Enhancement; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009434:Neural Pathways / Q000000981:diagnostic imaging; D010286:Paraventricular Hypothalamic Nucleus / Q000000981:diagnostic imaging* / Q000378:metabolism; D014697:Ventromedial Hypothalamic Nucleus / Q000000981:diagnostic imaging* / Q000378:metabolism
chemical_list: D020738:Leptin; D008345:Manganese
keywords: Hypothalamus; Leptin; Metabolic disease; Molecular imaging; Obesity