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Brain Structure and Function

, Volume 224, Issue 1, pp 99–110 | Cite as

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

  • Fumito Naganuma
  • Sathyajit S. Bandaru
  • Gianna Absi
  • Melissa J. Chee
  • Ramalingam VetrivelanEmail author
Original Article

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 Vglut2flox/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.

Keywords

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

Notes

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.

Author 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.

Funding

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

Compliance with ethical standards

Conflict of interest

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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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep MedicineHarvard Medical SchoolBostonUSA
  2. 2.Division of Pharmacology, Faculty of MedicineTohoku Medical and Pharmaceutical UniversitySendaiJapan
  3. 3.Department of NeuroscienceCarleton UniversityOttawaCanada

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