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Updated: Mar 14, 2026

Optogenetic Activation of Intrinsic Cardiac Autonomic Neurons in Excised Perfused Mouse Hearts
Published on: March 28, 2025
Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons
Olga Dergacheva1, Akihiro Yamanaka2, Alan R Schwartz3
1Department of Pharmacology and Physiology, The George Washington University, 2300 Eye Street, NW, Washington, DC 20037, USA.
Abstract:
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.
Insights
Orexin neurons influence heart rate by modulating cardiac vagal neurons (CVNs). Optogenetic stimulation revealed orexin neurons excite or inhibit CVNs, suggesting varied roles in parasympathetic cardiac regulation.
Area of Science:
- Neuroscience
- Cardiovascular Physiology
- Autonomic Nervous System Research
Background:
- Orexin neurons are recognized for enhancing sympathetic cardiovascular control.
- The specific role of orexin neurons in parasympathetic cardiac regulation is not well understood.
Purpose of the Study:
- To investigate the contribution of orexin neurons to parasympathetic cardiac control.
- To determine if orexin neurons directly influence cardiac vagal neurons (CVNs).
Main Methods:
- Used orexin-Cre transgenic rats for selective optogenetic targeting of orexin neurons with channelrhodopsin-2 (ChR2).
- Performed electrophysiological recordings of postsynaptic currents in CVNs within the dorsal motor nucleus of the vagus (DMV).
- Utilized photostimulation to activate ChR2-expressing orexin neurons and their projections.
Main Results:
- Optogenetic activation of orexin neurons induced reliable firing and large currents, confirming effective ChR2 expression and excitation.
- Photostimulation of orexin fibers in the DMV evoked short-latency postsynaptic currents in 36% of tested CVNs.
- These responses were heterogeneous, comprising 63% excitatory glutamatergic and 37% inhibitory GABAergic currents.
Conclusions:
- Orexin neurons can exert both excitatory and inhibitory influences on cardiac vagal neurons.
- Different subpopulations of orexin neurons may differentially regulate CVNs.
- These findings suggest a complex role for orexin neurons in the parasympathetic control of heart rate.
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