Neurovascular coupling and bilateral connectivity during NREM and REM sleep
- Pennsylvania State University, United States
Abstract
To understand how arousal state impacts cerebral hemodynamics and neurovascular coupling, we monitored neural activity, behavior, and hemodynamic signals in un-anesthetized, head-fixed mice. Mice frequently fell asleep during imaging, and these sleep events were interspersed with periods of wake. During both NREM and REM sleep, mice showed large increases in cerebral blood volume ([HbT]) and arteriole diameter relative to the awake state, two to five times larger than those evoked by sensory stimulation. During NREM, the amplitude of bilateral low-frequency oscillations in [HbT] increased markedly, and coherency between neural activity and hemodynamic signals was higher than the awake resting and REM states. Bilateral correlations in neural activity and [HbT] were highest during NREM, and lowest in the awake state. Hemodynamic signals in the cortex are strongly modulated by arousal state, and changes during sleep are substantially larger than sensory-evoked responses.
Data availability
Source data and code for generation of all figures can be found here:Code repository location: https://github.com/DrewLab/Turner_Gheres_Proctor_Drew_eLife2020Data repository location: https://doi.org/10.5061/dryad.6hdr7sqz5
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Neurovascular coupling and bilateral connectivity during NREM and REM sleepDryad Digital Repository, 10.5061/dryad.6hdr7sqz5.
Article and author information
Author details
Funding
National Institutes of Health (R01NS078168)
- Patrick J Drew
National Institutes of Health (R01NS079737)
- Patrick J Drew
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All procedures were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) of Pennsylvania State University (protocol # 201042827).
Copyright
© 2020, Turner et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Neurovascular coupling and bilateral connectivity during NREM and REM sleep
eLife 9:e62071.
https://doi.org/10.7554/eLife.62071
Further reading
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- Neuroscience
By influencing calcium homeostasis, local protein synthesis and the endoplasmic reticulum, a small protein called Rab10 emerges as a crucial cytoplasmic regulator of neuropeptide secretion.
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Dense core vesicles (DCVs) transport and release various neuropeptides and neurotrophins that control diverse brain functions, but the DCV secretory pathway remains poorly understood. Here, we tested a prediction emerging from invertebrate studies about the crucial role of the intracellular trafficking GTPase Rab10, by assessing DCV exocytosis at single-cell resolution upon acute Rab10 depletion in mature mouse hippocampal neurons, to circumvent potential confounding effects of Rab10’s established role in neurite outgrowth. We observed a significant inhibition of DCV exocytosis in Rab10-depleted neurons, whereas synaptic vesicle exocytosis was unaffected. However, rather than a direct involvement in DCV trafficking, this effect was attributed to two ER-dependent processes, ER-regulated intracellular Ca2+ dynamics, and protein synthesis. Gene Ontology analysis of differentially expressed proteins upon Rab10 depletion identified substantial alterations in synaptic and ER/ribosomal proteins, including the Ca2+ pump SERCA2. In addition, ER morphology and dynamics were altered, ER Ca2+ levels were depleted, and Ca2+ homeostasis was impaired in Rab10-depleted neurons. However, Ca2+ entry using a Ca2+ ionophore still triggered less DCV exocytosis. Instead, leucine supplementation, which enhances protein synthesis, largely rescued DCV exocytosis deficiency. We conclude that Rab10 is required for neuropeptide release by maintaining Ca2+ dynamics and regulating protein synthesis. Furthermore, DCV exocytosis appeared more dependent on (acute) protein synthesis than synaptic vesicle exocytosis.
