Journal article
Neuroanatomical organization and functional roles of PVN MC4R pathways in physiological and behavioral regulations
Molecular metabolism (Germany), Vol.55, 101401
11/2021
DOI: 10.1016/j.molmet.2021.101401
PMCID: PMC8689242
PMID: 34823066
Abstract
The paraventricular nucleus of hypothalamus (PVN) is an integrative center in the brain orchestrating a wide range of physiological and behavioral responses. While the PVN melanocortin 4 receptor (MC4R) signaling (PVNMC4R+) is undoubtedly involved in feeding regulation, the neuroanatomical organization of PVNMC4R+ connectivity and its role in other physiological regulations are not fully understood. Here we aimed to better characterize the input-output organization of PVNMC4R+ neurons and further test their physiological functions beyond feeding.
Using a combination of viral tools, we mapped PVNMC4R+ circuits and tested the effects of chemogenetic activation of PVNMC4R+ neurons on thermoregulation, cardiovascular control, and other behavioral responses beyond feeding.
We found that PVNMC4R+ neurons innervate many different brain regions known to be important not only for feeding but also for neuroendocrine and autonomic control of thermoregulation and cardiovascular function, including but not limited to the preoptic area, median eminence, parabrachial nucleus, pre-locus coeruleus, nucleus of solitary tract, ventrolateral medulla, and thoracic spinal cord. Contrary to these broad efferent projections, PVNMC4R+ neurons receive monosynaptic inputs mainly from other hypothalamic nuclei (preoptic area, arcuate and dorsomedial hypothalamic nuclei, supraoptic nucleus, and premammillary nucleus), the circumventricular organs (subfornical organ and vascular organ of lamina terminalis), the bed nucleus of stria terminalis, and the parabrachial nucleus. Consistent with their broad efferent projections, chemogenetic activation of PVNMC4R+ neurons not only suppressed feeding but also led to an apparent increase in heart rate, blood pressure and brown adipose tissue temperature. These physiological changes accompanied an acute transient hyperactivity followed by hypoactivity and resting-like behavior.
Our results clarify the neuroanatomical organization of PVNMC4R+ circuits and shed new light on the roles of PVNMC4R+ pathways in autonomic control of thermoregulation, cardiovascular function and biphasic behavioral activation.
•PVNMC4R+ neurons innervate brain regions involved in feeding as well as autonomic regulation.•Activation of PVNMC4R+ neurons increases BAT thermogenesis.•Activation of PVNMC4R+ neurons increases blood pressure and heart rate.•Activation of PVNMC4R+ neurons lead to transient hyperactivity followed by hypoactivity and resting-like behavior.
Details
- Title: Subtitle
- Neuroanatomical organization and functional roles of PVN MC4R pathways in physiological and behavioral regulations
- Creators
- Uday Singh - University of IowaJingwei Jiang - University of IowaKenji Saito - University of IowaBrandon A Toth - University of IowaJacob E Dickey - University of IowaSamuel R Rodeghiero - University of IowaYue Deng - University of IowaGuorui Deng - University of IowaBaojian Xue - University of IowaZhiyong Zhu - University of IowaLeonid V Zingman - University of IowaJoel C Geerling - University of IowaHuxing Cui - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular metabolism (Germany), Vol.55, 101401
- DOI
- 10.1016/j.molmet.2021.101401
- PMID
- 34823066
- PMCID
- PMC8689242
- NLM abbreviation
- Mol Metab
- ISSN
- 2212-8778
- eISSN
- 2212-8778
- Publisher
- Elsevier GmbH
- Grant note
- DOI: 10.13039/100000002, name: NIH; DOI: 10.13039/100000968, name: American Heart Association Inc
- Language
- English
- Date published
- 11/2021
- Academic Unit
- Neurology; Psychological and Brain Sciences; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Neurology (Pediatrics); Internal Medicine
- Record Identifier
- 9984197938702771
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