MEMRI detects neuronal activity and connectivity in hypothalamic neural circuit responding to leptin

Ulyanova, Anna, To, Xuan Vinh, Asad, A. B. M. A., Han, Weiping and Chuang, Kai-Hsiang (2017) MEMRI detects neuronal activity and connectivity in hypothalamic neural circuit responding to leptin. Neuroimage, 147 904-915. doi:10.1016/j.neuroimage.2016.10.012


Author Ulyanova, Anna
To, Xuan Vinh
Asad, A. B. M. A.
Han, Weiping
Chuang, Kai-Hsiang
Title MEMRI detects neuronal activity and connectivity in hypothalamic neural circuit responding to leptin
Journal name Neuroimage   Check publisher's open access policy
ISSN 1095-9572
1053-8119
Publication date 2017-02-15
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.neuroimage.2016.10.012
Open Access Status Not yet assessed
Volume 147
Start page 904
End page 915
Total pages 12
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
Subject 2808 Neurology
2805 Cognitive Neuroscience
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 Ca channel activity, neuronal activation or connectivity in the leptin signaling pathway are not clear. By blocking L-type Ca 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.
Formatted 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.
Keyword Hypothalamus
Leptin
Metabolic disease
Molecular imaging
Obesity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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