Elevated serotonin in mouse spinal dorsal horn is pronociceptive

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 14, 2023

Serotonergic neurons in the rostral ventral medulla (RVM) contribute to bidirectional control of pain through modulation spinal and trigeminal nociceptive networks. Deficits this pathway are believed pathological states, but whether changes serotonergic mechanisms pro or anti-nociceptive debated. We used a combination optogenetics fiber photometry examine these more closely. find that optogenetic activation RVM afferents cord naïve mice produces mechanical hypersensitivity conditioned place aversion. Neuropathic pain, produced by chronic constriction injury infraorbital nerve (CCI-ION), evoked tonic increase serotonin concentrations within nucleus caudalis (SpVc), measured with liquid chromatography-tandem mass spectroscopy (LC-MS/MS). By contract, CCI-ION had no effect on phasic transients SpVc, noxious pinch, sensor. These findings suggest release is pronociceptive an sustained signaling, rather than event driven increases, potentiate nociception models pain.

Language: Английский

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Lateral lamina V projection neuron axon collaterals connect sensory processing across the dorsal horn of the mouse spinal cord

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 21, 2024

Spinal projection neurons (PNs) are defined by long axons that travel from their origin in the spinal cord to brain where they relay sensory information body. The existence and function of a substantial axon collateral network, also arising PNs remaining within cord, is less well appreciated. Here we use retrograde viral transduction strategy characterise novel subpopulation deep dorsal horn spinoparabrachial neurons. Brainbow assisted analysis confirmed virally labelled PN cell bodies formed discrete column lateral part Lamina V (LV lat) adjoining white matter. These exhibited large dendritic territories biased regions ventral body extending considerable rostrocaudal distances. Optogenetic activation LV Lat this population mediates widespread signalling throughout circuits, including superficial horn. This was demonstrated with patch clamp recordings during photostimulation, range direct indirect connections identified evidence postsynaptic inhibitory interneurons. Together, these findings confirm role for local processing, as signals brain.

Language: Английский

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An Intra-brainstem Circuit for Pain-induced Inhibition of Itch

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 4, 2024

Abstract Pain and itch are unpleasant distinct sensations that give rise to behaviors such as reflexive withdrawal scratching in humans mice. Interestingly, it has been observed pain modulate through the neural circuits housed brain spinal cord. However, we yet fully understand identities of mechanisms by which specific mediate pain-induced modulation itch. Independent studies indicate brainstem nuclei lateral parabrachial nucleus (LPBN) rostral ventromedial medulla (RVM) important for suppression painful stimuli. Here, using mouse viral genetics, rabies tracing, chemogenetics, calcium imaging, show synaptic connections between LPBN RVM plays an instrumental role interactions Notably, found neurons express gene encoding substance P receptor, Tacr1 (LPBN ), synapse onto Tacr1-expressing (RVM ). The were be nociceptive, sufficient inhibiting itch, necessary suppression. Moreover, brain-wide anterograde retrograde tracing studies, bidirectionally connected with LPBN, periaqueductal gray (PAG), hypothalamic area (LHA). Thus, together, our data integrate nociceptive information itch-induced can physiological effects their downstream targets.

Language: Английский

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Potentiation of active locomotor state by spinal-projecting serotonergic neurons

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 28, 2024

Animals produce diverse motor actions that enable expression of context-appropriate behaviors. Neuromodulators facilitate behavioral flexibility by altering the temporal dynamics and output neural circuits. Discrete populations serotonergic (5-HT) neurons target circuits in brainstem spinal cord, but their role control behavior is unclear. Here we define pre- post-synaptic organization spinal-projecting system a locomotor control. We show while forebrain-targeting 5-HT decrease activity during locomotion, subpopulations projecting increase context-dependent manner. Optogenetic activation ventrally does not trigger initiation movement, rather enhances speed duration ongoing locomotion over extended time scales. These findings indicate descending potentiates demonstrate for modulating

Language: Английский

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Rostral ventral medulla circuits regulate both the sensory and affective dimensions of neuropathic pain: a commentary on Dogrul et al.

Pain, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Language: Английский

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