Melanin-concentrating hormone neurons promote rapid eye movement sleep independent of glutamate release

Naganuma, Fumito; Bandaru, Sathyajit S.; Absi, Gianna; Chee, Melissa J.; Vetrivelan, Ramalingam

doi:10.1007/s00429-018-1766-2

Original Article
Published: 03 October 2018

Melanin-concentrating hormone neurons promote rapid eye movement sleep independent of glutamate release

Fumito Naganuma^1,2^na1,
Sathyajit S. Bandaru¹^na1,
Gianna Absi¹,
Melissa J. Chee³ &
Ramalingam Vetrivelan ORCID: orcid.org/0000-0002-6376-3641¹

Brain Structure and Function volume 224, pages 99–110 (2019)Cite this article

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Abstract

Neurons containing melanin-concentrating hormone (MCH) in the posterior lateral hypothalamus play an integral role in rapid eye movement sleep (REMs) regulation. As MCH neurons also contain a variety of other neuropeptides [e.g., cocaine- and amphetamine-regulated transcript (CART) and nesfatin-1] and neurotransmitters (e.g., glutamate), the specific neurotransmitter responsible for REMs regulation is not known. We hypothesized that glutamate, the primary fast-acting neurotransmitter in MCH neurons, is necessary for REMs regulation. To test this hypothesis, we deleted vesicular glutamate transporter (Vglut2; necessary for synaptic release of glutamate) specifically from MCH neurons by crossing MCH-Cre mice (expressing Cre recombinase in MCH neurons) with Vglut2^flox/flox mice (expressing LoxP-modified alleles of Vglut2), and studied the amounts, architecture and diurnal variation of sleep-wake states during baseline conditions. We then activated the MCH neurons lacking glutamate neurotransmission using chemogenetic methods and tested whether these MCH neurons still promoted REMs. Our results indicate that glutamate in MCH neurons contributes to normal diurnal variability of REMs by regulating the levels of REMs during the dark period, but MCH neurons can promote REMs even in the absence of glutamate.

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Acknowledgements

We thank Quan Ha, Minh Ha and Celia Gagliardi for excellent technical assistance and Dr. Daniel Kroeger for his help with histology imaging. We also thank Dr. Eleftheria Maratos-Flier (Department of Medicine, Beth Israel Deaconess Medical Center, Boston) for providing the rabbit anti-MCH antibody.

Funding

This work was supported by National Institutes of Health Grants [R21-NS074205, R01-NS088482 (to RV)].

Author information

Fumito Naganuma and Sathyajit S. Bandaru: Equal contribution.

Authors and Affiliations

Department of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, 3 Blackfan Circle, Center for Life Science # 717, Boston, MA, 02215, USA
Fumito Naganuma, Sathyajit S. Bandaru, Gianna Absi & Ramalingam Vetrivelan
Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1, Fukumuro, Miyagino-ku, Sendai, 983-8536, Japan
Fumito Naganuma
Department of Neuroscience, Carleton University, Ottawa, ON, K1S 5B6, Canada
Melissa J. Chee

Authors

Fumito Naganuma
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Sathyajit S. Bandaru
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Gianna Absi
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Melissa J. Chee
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Ramalingam Vetrivelan
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Contributions

Conceived and designed the experiments: FN and RV; Performed the experiments: FN, SB, GA and RV; Analyzed the data: FN, SB, GA and RV; Written the manuscript: FN, SB and RV with input from all authors. Provided key reagents: MC; Supervision: RV.

Corresponding author

Correspondence to Ramalingam Vetrivelan.

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This was not an industry-supported study. The authors declare that they have no competing interests.

Research involving human participants and/or animals

Care of the animals met National Institutes of Health standards, as set forth in the Guide for the Care and Use of Laboratory Animals, and all protocols were approved by the BIDMC Institutional Animal Care and Use Committee.

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Naganuma, F., Bandaru, S.S., Absi, G. et al. Melanin-concentrating hormone neurons promote rapid eye movement sleep independent of glutamate release. Brain Struct Funct 224, 99–110 (2019). https://doi.org/10.1007/s00429-018-1766-2

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Received: 23 March 2018
Accepted: 27 September 2018
Published: 03 October 2018
Issue Date: 15 January 2019
DOI: https://doi.org/10.1007/s00429-018-1766-2

Keywords

Paradoxical sleep
Lateral hypothalamus
Conditional knockout
Chemogenetics
Locomotor activity
Body temperature
Diurnal rhythms