A mouse DRG genetic toolkit reveals morphological and physiological diversity of somatosensory neuron subtypes

Cell, Год журнала: 2024, Номер 187(6), С. 1508 - 1526.e16

Опубликована: Март 1, 2024

Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from periphery to CNS has been challenging with existing tools. Here, we develop curate mouse genetic toolkit that allows for interrogating properties functions distinct cutaneous targeting subtypes. These tools have enabled broad morphological analysis, which revealed axon arborization areas branching patterns transcriptionally Moreover, in vivo physiological analysis each subtype threshold range responses mechanical and/or thermal stimuli. findings support model morphologically physiologically sensory tile stimulus space collectively encode wide natural

Язык: Английский

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Basic mechanisms of itch

Journal of Allergy and Clinical Immunology, Год журнала: 2023, Номер 152(1), С. 11 - 23

Опубликована: Май 17, 2023

Язык: Английский

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Representation and control of pain and itch by distinct prefrontal neural ensembles

Neuron, Год журнала: 2023, Номер 111(15), С. 2414 - 2431.e7

Опубликована: Май 23, 2023

Язык: Английский

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Cancer immunometabolism: advent, challenges, and perspective

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Апрель 5, 2024

Abstract For decades, great strides have been made in the field of immunometabolism. A plethora evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism center stage innate and adaptive immunomodulation. Given this, we focus changes immunometabolism, a converging series biochemical events that alters immune cell function, propose roles played by diversified metabolic derivatives enzymes, emphasize key metabolism-related checkpoints distinct types, discuss ongoing upcoming realities treatment. It is expected future research will reduce current limitations immunotherapy provide positive hand responses exert broader therapeutic role.

Язык: Английский

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A DRG genetic toolkit reveals molecular, morphological, and functional diversity of somatosensory neuron subtypes

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Апрель 23, 2023

Summary Mechanical and thermal stimuli acting on the skin are detected by morphologically physiologically distinct sensory neurons of dorsal root ganglia (DRG). Achieving a holistic view how this diverse neuronal population relays information from to central nervous system (CNS) has been challenging with existing tools. Here, we used transcriptomic datasets mouse DRG guide development curation genetic toolkit interrogate transcriptionally defined neuron subtypes. Morphological analysis revealed unique cutaneous axon arborization areas branching patterns each subtype. Physiological showed that subtypes exhibit thresholds ranges responses mechanical and/or stimuli. The somatosensory toolbox thus enables comprehensive phenotyping most principal Moreover, our findings support coding scheme in which activation tile multiple dimensions stimulus space.

Язык: Английский

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Distinct local and global functions of mouse Aβ low-threshold mechanoreceptors in mechanical nociception

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 4, 2024

Abstract The roles of Aβ low-threshold mechanoreceptors (LTMRs) in transmitting mechanical hyperalgesia and alleviating chronic pain have been great interest but remain contentious. Here we utilized intersectional genetic tools, optogenetics, high-speed imaging to specifically examine functions Split Cre labeled mouse Aβ-LTMRs this regard. Genetic ablation - increased nociception not thermosensation both acute inflammatory conditions, indicating a modality-specific role gating nociception. Local optogenetic activation -Aβ-LTMRs triggered after tissue inflammation, whereas their broad at the dorsal column still alleviated hypersensitivity inflammation. Taking all data into consideration, propose model, which play distinctive local global or pain, respectively. Our model suggests strategy plus inhibition for treating hyperalgesia.

Язык: Английский

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Critical Players and Therapeutic Targets in Chronic Itch

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(17), С. 9935 - 9935

Опубликована: Сен. 1, 2022

Chronic itch is one of the most prominent clinical characteristics diverse systematic diseases. It a devastating sensation in pathological Despite its importance, there are no FDA-labelled drugs specifically geared toward chronic itch. The associated complex pathogenesis and causes escalate to being top challenges healthcare. Humanized antibodies against IL-13, IL-4, IL-31 proved effective treatment itch-associated atopic dermatitis but remain be validated There still satisfactory anti-itch therapeutics available itch-related neuropeptides including GRP, BNP, SST, CGRP, SP. newly identified potential targets OSM, NMB, glutamate, periostin, Serpin E1 have opened new avenues for therapeutic development. Proof-of-principle studies been successfully performed on antagonists these proteins their receptors animal models. Their translational interventions humans need evaluated. great importance summarize compare emerging knowledge pathways promote development novel therapeutics. goal this review analyze different physiologies pathophysiologies mediators, whilst assessing suitability as discussing future

Язык: Английский

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MrgprA3 neurons drive cutaneous immunity against helminths through selective control of myeloid-derived IL-33

Nature Immunology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

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Itch-specific neurons in the ventrolateral orbital cortex selectively modulate the itch processing

Science Advances, Год журнала: 2022, Номер 8(30)

Опубликована: Июль 29, 2022

Itch is a cutaneous sensation that critical in driving scratching behavior. The long-standing question of whether there are specific neurons for itch modulation inside the brain remains unanswered. Here, we report subpopulation itch-specific ventrolateral orbital cortex (VLO) distinct from pain-related neurons. Using Tet-Off cellular labeling system, showed local inhibition or activation these VLO significantly suppressed enhanced itch-induced scratching, respectively, whereas intervention did not affect pain. Conversely, suppression pain-specific affected pain but itch. Moreover, fiber photometry and immunofluorescence verified itch- their functional activity histological location. In addition, downstream targets were different. Together, present study uncovers an important specifically modulates processing.

Язык: Английский

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Pain and itch coding mechanisms of polymodal sensory neurons

Cell Reports, Год журнала: 2023, Номер 42(11), С. 113316 - 113316

Опубликована: Окт. 26, 2023

Pain and itch coding mechanisms in polymodal sensory neurons remain elusive. MrgprD+ represent a major population mediate both mechanical pain nonhistaminergic itch. Here, we show that chemogenetic activation of elicited pain- itch-related behavior dose-dependent manner, revealing an unanticipated compatibility between neurons. While VGlut2-dependent glutamate release is required for transmission from neurons, the neuropeptide neuromedin B (NMB) selectively signaling. Electrophysiological recordings further demonstrated synergizes with NMB to excite NMB-sensitive postsynaptic Ablation these spinal abolished signals without affecting signals, suggesting dedicated itch-processing central circuit. These findings reveal distinct neurotransmitters neural circuit requirements signaling providing new insights on processing

Язык: Английский

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