Neuron: High blood pressure, can't sleep? Scientists have revealed that the pressure-reflex neural circuits that lower blood pressure promote sleep

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During the transition from wakefulness to sleep, the body undergoes significant changes: physical motor activity and skeletal muscle tone decrease, and spontaneous movement activity is also strongly reduced, causing physiological changes
such as lower blood pressure and slowed heart rate.
Lack of sleep increases the risk
of cardiovascular diseases such as hypertension and coronary heart disease.

The barbaric reflex is an important negative feedback loop neural mechanism of the cardiovascular regulatory system: an increase in arterial blood pressure sensed by peripheral baroreceptors transmits information to the nucleus solitary pulp (NST), triggering compensatory changes in cardiac and vasoconstrictive activity, thereby lowering blood pressure
.

On September 27, 2022, Yang Dan of the University of California, Howard Hughes School of Medicine, revealed the mechanism by which the cardiovascular stress reflex loop promotes sleep: activating both NST ➟ Amb and NST➟CVLM ➟RVLM both promote sleep
.

1

Genetically tagged baroreceptor-sensitive neurons

Phenylephrine (PE) is a vasoconstrictor that acts on adrenergic receptors in blood vessels to cause a decrease
in arterial blood pressure and heart rate.
The researchers achieved PE-activated NST neurons (NST-PE-TRAP neurons) through cre tool mice, most of which are excitatory neurons and about a quarter of which are inhibitory neurons
.
In addition, about half of the activated neurons express cocaine-amphetamine transcriptional regulatory peptide (CART
).

NST-PE-TRAP neurons are able to respond to changes
in blood pressure and heart rate within subseconds.
Fiber optic calcium imaging technology found that CART-positive neuronal activity in the NST region after PE injection increased with increased
blood pressure.
Viral tracing experiments found that both NST-PE-TRAP neurons and NST CART-positive neurons in the NST region received input from baroreceptors, so these two types of neurons belong to baroreceptor-sensitive neurons
.

Figure 1: Genetically labeled PE-activated baroreceptor-sensitive neurons

2

Stressoreceptor-sensitive neurons regulate sleep

Chemical genetics chronic activation of NST-PE-TRAP neurons, which can cause a decrease in blood pressure and heart rate in mouse arteries, an increase in the time of the non-rapid eye movement period, and a decrease in
the time of awakening.
Chronic activation of CART-positive neurons in the NST region is also able to lower blood pressure and heart rate, and promote non-REM sleep
.
Virus-specific inducement of CART-positive neuronal apoptosis in the NST region decreased sensitivity to stress reflexes in mice, and non-REM sleep events decreased
.

Optogenetic techniques that acutely activate NST-PE-TRAP neurons or CART-positive neurons in the NST region can reduce blood pressure and increase non-REM sleep, while inhibition of these neurons promotes wakefulness and reduces non-REM sleep
.

Figure 2: Activation of baroreceptor-sensitive neurons to promote sleep

3

The baroreceptor loop regulates sleep

Two basic pathways of baroreceptor reflexes: glutamatergic projection of NST onto the endomedullary nucleus ductus (Amb) activates preganglidinal parasympathetic neurons, resulting in a slowdown in heart rate (NST ➟ Amb); NST glutamate can be projected to the lateral region of the caudal medulla oblongata (CVLM) to activate inhibitory neurons, thereby inhibiting the excitation of adrenergic neurons by the ventral lateral region of the ventral medulla oblongata (RVLM), resulting in a decrease in vasomotor tone and blood pressure (NST➟CVLM ➟RVLM neural circuit).


Viral tracing experiments found that CART-positive neurons in the NST region were projected onto CVLM inhibitory neurons
.
Light activation of CVLM inhibitory neurons or inhibition of dopaminergic neurons in the RVLM region can significantly promote non-REM sleep
.
In addition, CART-positive neurons in the NST region are also projected onto cholinergic neurons
in the suspected nucleus region.
Chronic activation of cholinergic neurons in the suspected nucleus promotes non-REM sleep
.

Figure 3: Activating the Pressure Reflex Pathway to Promote Sleep

summary

Studies have shown that sleep-wake states can affect the negative feedback loop
of pressure reflex.
In this paper, it was found that activating the brainstem pressure reflex loop in the mouse brain can exercise the normal hypotensive and heart-rate-lowering functions, as well as the additional function
of promoting sleep.

【References】

1.
Yao et al.
, Cardiovascular baroreflex circuit moonlights in sleep control, Neuron (2022), 

https://doi.
org/10.
1016/j.
neuron.
2022.
08.
027

The images in the article are from references