Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons
Open accessAbstract
Orexin neurons are known to augment the sympathetic control of cardiovascular function, however the role of orexin neurons in parasympathetic cardiac regulation remains unclear. To test the hypothesis that orexin neurons contribute to parasympathetic control we selectively expressed channelrhodopsin-2 (ChR2) in orexin neurons in orexin-Cre transgenic rats and examined postsynaptic currents in cardiac vagal neurons (CVNs) in the dorsal motor nucleus of the vagus (DMV). Simultaneous photostimulation and recording in ChR2-expressing orexin neurons in the lateral hypothalamus resulted in reliable action potential firing as well as large whole-cell currents suggesting a strong expression of ChR2 and reliable optogenetic excitation. Photostimulation of ChR2-expressing fibers in the DMV elicited short-latency (ranging from 3.2ms to 8.5ms) postsynaptic currents in 16 out of 44 CVNs tested. These responses were heterogeneous and included excitatory glutamatergic (63%) and inhibitory GABAergic (37%) postsynaptic currents. The results from this study suggest different sub-population of orexin neurons may exert diverse influences on brainstem CVNs and therefore may play distinct functional roles in parasympathetic control of the heart.
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LH orexin neurons project to the DMV, and parasympathetic vagus input dampens hepatic inflammation; these effects may be exerted through DMV parasympathetic neurons.
“From the LH, these effects may be exerted through parasympathetic neurons in the DMV, as LH orexin neurons project to the DMV146 and parasympathetic input from the vagus nerve dampens hepatic inflammation147.”
From Central regulation of stress-evoked peripheral immune responses (2023) · cites this paper as [146]
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Central regulation of stress-evoked peripheral immune responses
Chan, K. L., Poller, W. C., Swirski, F. K., & Russo, S. J. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00729-2 · Cited by 207 · see citing works
- Authors
- Dergacheva, O., Yamanaka, A., Schwartz, A. R., Polotsky, V. Y., & Mendelowitz, D.
- Affiliations
- George Washington University (US)
- Research Institute of Environmental Medicine, Nagoya University (JP)
- Johns Hopkins University (US)
- Corresponding author
- Dergacheva, Olga
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 339
- Pages
- 47-53
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC5118111
- OpenAlex
- W2526062040
- Cited by
- 28
- References
- 45
- Citations by year
- 2025: 2 · 2024: 6 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 2
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (HL 72006)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- orexin neurons, cardiac vagal neurons, dorsal motor nucleus of the vagus, lateral hypothalamus, channelrhodopsin-2, optogenetic stimulation, postsynaptic currents, glutamatergic synapses, GABAergic synapses, cardiovascular regulation
- MeSH terms
- Orexins, Action Potentials, Animals, Brain Stem, Female, gamma-Aminobutyric Acid, Hypothalamus, Male, Neural Pathways, Neurons, Vagus Nerve, Glutamic Acid, Tissue Culture Techniques, Synaptic Potentials, Rats, Transgenic, Optogenetics
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