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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurosci. | doi: 10.3389/fnins.2019.00755

Differential role of pontomedullary glutamatergic neuronal populations in sleep-wake control

  • 1University of Massachusetts Medical School, United States
  • 2University of Massachusetts Medical School, United States
  • 3University of Massachusetts Medical School, United States

Parafacial zone (PZ) GABAergic neurons play a major role in slow-wave-sleep (SWS), also called non-rapid eye movement (NREM) sleep. The parafacial zone also contains glutamatergic neurons expressing the vesicular transporter for glutamate, isoform 2 (Vglut2). We hypothesized that PZ Vglut2-expressing (PZVglut2) neurons are also involved in sleep control, playing a synergistic role with PZ GABAergic neurons. To test this hypothesis, we specifically activated PZVglut2 neurons using the excitatory chemogenetic receptor hM3Dq. Anatomical inspection of the injection sites revealed hM3Dq transfection in PZ, parabrachial nucleus (PB), sublaterodorsal nucleus (SLD) or various combinations of these three brain areas. Consistent with the known wake- and REM sleep-promoting role of PB and SLD, respectively, chemogenetic activation of PBVglut2 or SLDVglut2 resulted in wake or REM sleep enhancement. Chemogenetic activation of PZVglut2 neurons did not affect sleep-wake phenotype during the mouse active period but increased wakefulness and REM sleep, similar to PBVglut2 and SLDVglut2 activation, during the rest period. To definitively confirm the role of PZVglut2 neurons, we used a specific marker for PZVglut2 neurons, Phox2B. Chemogenetic activation of PZPhox2B neurons did not affect sleep-wake phenotype, indicating that PZ glutamatergic neurons are not sufficient to affect sleep-wake cycle. These results indicate that PZ glutamatergic neurons are not involved in sleep-wake control.

Keywords: neuronal circuitry, DREADDs, brainstem, Parafacial zone, sleep-wake control, sublaterodorsal nucleus, parabrachial nucleus

Received: 30 Mar 2019; Accepted: 08 Jul 2019.

Edited by:

Takeshi Sakurai, University of Tsukuba, Japan

Reviewed by:

Radhika Basheer, Harvard Medical School, United States
Hiromasa Funato, Toho University, Japan  

Copyright: © 2019 Erickson, Ferrari, Gompf and Anaclet. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Christelle Anaclet, University of Massachusetts Medical School, Worcester, United States, Christelle.Anaclet@umassmed.edu