Neuron Cardiovascular Disease Affects Sleep! Academician Danyang's team reveals the mechanism by which the cardiovascular pressure reflex circuit regulates sleep

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The transition from wakefulness to sleep has undergone profound changes
in the state of the animal's brain and motor activity.
In addition to somatic motor activity and decreased skeletal muscle tone, spontaneous motor activity is also strongly reduced, leading to a decrease in blood pressure, a slowing of the heart rate, and other physiological changes
.

Sleep disorders are known to be associated
with cardiovascular diseases such as high blood pressure and coronary heart disease.
However, the mechanism link between sleep and cardiovascular health is still poorly understood, especially at the level of neural circuits
.
On September 27, 2022, the UC Berkeley Danyang team published a research paper titled "Cardiovascular baroreflex circuit moonlights in sleep control" online in the journal Neuron, which demonstrated that the pressure reflex circuit, previously thought to be the basic feedback mechanism of cardiovascular homeostasis, also contributes to sleep-wake brain state regulation
.
Sleep disorders are closely related to
cardiovascular disease.
An important neural mechanism of cardiovascular regulation is the pressure reflex, a negative feedback loop in which elevated arterial blood pressure perceived by peripheral baroreceptors is transmitted to nucleus of the solitary tract (NST), triggering compensatory changes in the heart and vasoconstrictive activity to lower blood pressure
。 There are two basic pathways to the stress reflex: glutamatergic projection from NST to the ambiguous nucleus (cranial motor nucleus) activates cholinergic preganglionic parasympathetic neurons, resulting in a decrease in heart rate; NST glutamic acid is projected onto caudal ventrolateral medulla (CVLM) activates GABAergic neurons, thereby inhibiting sympathophonic excitatory adrenergic neurons in the lateral ventro-medulla (RVLM) of the medulla, resulting in reduced
vasomotor tone and blood pressure.
It is well known that the stress reflex is regulated
by the sleep-wake state of the brain.
For example, some studies have shown that during non-rapid eye movement (non-REM, NREM) sleep, the pressure reflex set point is significantly lower than during waking hours, but the sensitivity (measured by linear regression slope between decreased heart rate and elevated blood pressure) is higher; Both of these changes can lead to a drop in
blood pressure.
The effect of brain state on stress reflexes may be mediated by input from midbrain and forebrain regions such as periductal gray matter and hypothalamus, both of which contain sleep-wake regulatory neurons
.
However, it is unclear whether neural circuits specifically used for cardiovascular regulation will in turn affect brain states
.
Although there were some reports a few decades ago that mechanical or electrical stimulation of peripheral baroreceptors can induce sleep-like states, this effect is thought to be limited to anesthesia conditions, and the underlying circuit mechanisms remain unknown
.
This study shows that the cardiovascular pressure reflex circuit makes a significant contribution
to sleep regulation in free-moving mice.
The researchers tagged NST neurons activated by pharmacologically induced increases in blood pressure by using activity-dependent genetic markers and confirmed their stress sensitivity
through photopolar recording and calcium imaging.
Interestingly, the chemical genetics or optogenetic activation of labeled NST neurons promotes non-REM sleep
in addition to lowering blood pressure and heart rate.
GABAergic neurons in the lateral lateral caudal end of the medulla oblongula (CVLM) (NST for downstream targets of vasoconstrictive pressure reflexes) also promote non-REM sleep, in part by promoting adrenergic neurons by inhibiting sympathetic excitation and arousal in the lateral ventral side of the head of the medulla oblongata (RVLM
).
In summary, this study used activity-dependent genetic markers to label NST neurons
activated by elevated blood pressure caused by PE.
In addition to lowering blood pressure and heart rate, the chemical genetics or optogenetic activation of these neurons promotes NREM sleep
.
Activating their targets – CVLM→ RVLM vasomotor pathways and Amb cardiac pathways also promote NREM sleep
.
A previous study showed that hypothalamic neurons activated by warm temperatures lead to a decrease in body temperature and increased sleep in NREM, suggesting a common mechanism
of autonomic and sleep control.
The findings suggest that lower brainstem neurons responsible for basic cardiovascular reflexes are also part of the sleep regulation mechanism, and that a key component of the cardiovascular stress reflex circuit is also a component
of sleep-wake brain state regulation.
Original link: https://doi.
org/10.
1016/j.
neuron.
2022.
08.
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