Descending locus coeruleus noradrenergic signaling to spinal astrocyte subset is required for stress-induced pain facilitation

Опубликована: Март 13, 2025

It is known that stress powerfully alters pain, but its underlying mechanisms remain elusive. Here, we identified a circuit, locus coeruleus descending noradrenergic neurons projecting to the spinal dorsal horn (LC →SDH -NA neurons), activated by acute exposure restraint and required for stress-induced mechanical pain hypersensitivity in mice. Interestingly, primary target of NA released from LC -NAergic terminals causing was α 1A -adrenaline receptors (α Rs) Hes5-positive (Hes5 + ) astrocytes located SDH, an astrocyte subset has ability induce sensitization. Furthermore, activation Hes5 reduced activity SDH-inhibitory (SDH-INs) have inhibitory role processing. This astrocytic reduction IN canceled A 1 -adenosine receptor (A R)-knockdown SDH-INs, R-knockdown suppressed caused stress. Therefore, our findings suggest neuronal signaling SDH subsequent SDH-IN are essential facilitation

Язык: Английский

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Descending locus coeruleus noradrenergic signaling to spinal astrocyte subset is required for stress-induced pain facilitation

Опубликована: Март 13, 2025

It is known that stress powerfully alters pain, but its underlying mechanisms remain elusive. Here, we identified a circuit, locus coeruleus descending noradrenergic neurons projecting to the spinal dorsal horn (LC →SDH -NA neurons), activated by acute exposure restraint and required for stress-induced mechanical pain hypersensitivity in mice. Interestingly, primary target of NA released from LC -NAergic terminals causing was α 1A -adrenaline receptors (α Rs) Hes5-positive (Hes5 + ) astrocytes located SDH, an astrocyte subset has ability induce sensitization. Furthermore, activation Hes5 reduced activity SDH-inhibitory (SDH-INs) have inhibitory role processing. This astrocytic reduction IN canceled A 1 -adenosine receptor (A R)-knockdown SDH-INs, R-knockdown suppressed caused stress. Therefore, our findings suggest neuronal signaling SDH subsequent SDH-IN are essential facilitation

Язык: Английский

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The Duality of Astrocyte Neuromodulation: Astrocytes Sense Neuromodulators and Are Neuromodulators

Journal of Neurochemistry, Год журнала: 2025, Номер 169(4)

Опубликована: Апрель 1, 2025

ABSTRACT Neuromodulation encompasses different processes that regulate neuronal and network function. Classical neuromodulators originating from long‐range nuclei, such as acetylcholine, norepinephrine, or dopamine, act with a slower time course wider spatial range than fast synaptic transmission action potential firing. Accumulating evidence in vivo indicates astrocytes, which are known to actively participate function at tripartite synapses, also involved neuromodulatory processes. The present article reviews recent findings obtained indicating astrocytes express receptors for elevate their internal calcium stimulate the release of gliotransmitters, function, hence mediate, least partially, effects neuromodulators. In addition, we propose local support by spatially temporally integrating signals neural presence astrocyte‐neuron hysteresis loops suggests astrocyte–neuron interaction synapses scales up astrocyte–neuronal networks modulate We finally sense environmental conditions, including states, provide homeostatic control maximizes dynamic activity. summary, critical mediating neuromodulators, they homeostasis thus optimizing information processing brain. Hence, ongoing activity along and, acting inform neurons about state system external world. image

Язык: Английский

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Characterization of the Astrocyte Calcium Response to Norepinephrine in the Ventral Tegmental Area

Cells, Год журнала: 2024, Номер 14(1), С. 24 - 24

Опубликована: Дек. 30, 2024

Astrocytes from different brain regions respond with Ca

Язык: Английский

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Descending locus coeruleus noradrenergic signaling to spinal astrocyte subset is required for stress-induced pain facilitation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 14, 2024

Abstract It is known that stress powerfully alters pain, but its underlying mechanisms remain elusive. Here, we identified a circuit, locus coeruleus descending noradrenergic neurons projecting to the spinal dorsal horn (LC →SDH -NA neurons), activated by acute exposure restraint and required for stress-induced mechanical pain hypersensitivity in mice. Interestingly, primary target of NA released from LC -NAergic terminals causing was α 1A -adrenaline receptors (α Rs) Hes5-positive (Hes5 + ) astrocytes located SDH, an astrocyte subset has ability induce sensitization. Furthermore, activation Hes5 reduced activity SDH-inhibitory (SDH-INs) have inhibitory role processing. This astrocytic reduction IN canceled A 1 -adenosine receptor (A R)-knockdown SDH-INs, R-knockdown suppressed caused stress. Therefore, our findings suggest neuronal signaling SDH subsequent SDH-IN are essential facilitation

Язык: Английский

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