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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Parvalbumin Neurons in Zona Incerta Regulate Itch in Mice

Frontiers in Molecular Neuroscience, Год журнала: 2022, Номер 15

Опубликована: Март 1, 2022

Pain and itch are intricately entangled at both circuitry behavioral levels. Emerging evidence indicates that parvalbumin (PV)-expressing neurons in zona incerta (ZI) critical for promoting nocifensive behaviors. However, the role of these modulation remains elusive. Herein, by combining FOS immunostaining, fiber photometry, chemogenetic manipulation, we reveal ZI PV act as an endogenous negative diencephalic modulator processing. Morphological data showed histamine chloroquine stimuli induced expression neurons. The activation was further supported increased calcium signal upon scratching behavior evoked acute itch. Behavioral indicated reduced behaviors related to histaminergic non-histaminergic Similar neural activity modulatory were seen mice with chronic atopic dermatitis. Together, our study provides direct regulating itch, identifies a potential target remedy

Язык: Английский

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Orexin neurons play contrasting roles in itch and pain neural processing via projecting to the periaqueductal gray

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Март 8, 2024

Abstract Pain and itch are recognized as antagonistically regulated sensations; pain suppresses itch, whilst inhibition enhances itch. The neural mechanisms at the central nervous system (CNS) underlying these pain-itch interactions still need to be explored. Here, we revealed contrasting role of orexin-producing neurons (ORX neurons) in lateral hypothalamus (LH), which while enhancing processing, by applying optogenetics acute pruritus model. We also that circuit ORX from LH periaqueductal gray regions served modulation processing using optogenetic terminal techniques. Additionally, an atopic dermatitis model, confirmed involvement regulating chronic could lead a novel therapeutic target for persistent clinical settings. Our findings provide new insight into mechanism antagonistic regulation between CNS.

Язык: Английский

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An insular cortical circuit required for itch sensation and aversion

Current Biology, Год журнала: 2024, Номер 34(7), С. 1453 - 1468.e6

Опубликована: Март 13, 2024

Язык: Английский

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Kappa opioids inhibit spinal output neurons to suppress itch

Science Advances, Год журнала: 2024, Номер 10(39)

Опубликована: Сен. 25, 2024

Itch is a protective sensation that drives scratching. Although specific cell types have been proposed to underlie itch, the neural basis for itch remains unclear. Here, we used two-photon Ca 2+ imaging of dorsal horn visualize neuronal populations are activated by itch-inducing agents. We identify convergent population spinal interneurons recruited diverse itch-causing stimuli represents subset neurons express gastrin-releasing peptide receptor (GRPR). Moreover, find conveyed brain via GRPR-expressing output target lateral parabrachial nuclei. then show kappa opioid agonist nalfurafine relieves selectively inhibiting GRPR spinoparabrachial neurons. These experiments provide population-level view respond pruritic stimuli, pinpoint convey brain, and cellular agonists inhibition itch.

Язык: Английский

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A non-canonical retina-ipRGCs-SCN-PVT visual pathway for mediating contagious itch behavior

Cell Reports, Год журнала: 2022, Номер 41(1), С. 111444 - 111444

Опубликована: Окт. 1, 2022

Contagious itch behavior informs conspecifics of adverse environment and is crucial for the survival social animals. Gastrin-releasing peptide (GRP) its receptor (GRPR) in suprachiasmatic nucleus (SCN) hypothalamus mediates contagious mice. Here, we show that intrinsically photosensitive retina ganglion cells (ipRGCs) convey visual information, independently melanopsin, from to GRP neurons via PACAP-PAC1R signaling. Moreover, GRPR relay information paraventricular thalamus (PVT). Surprisingly, neither cortex nor superior colliculus involved itch. In vivo calcium imaging extracellular recordings reveal itch-specific neural dynamics neurons. Thus, propose retina-ipRGC-SCN-PVT pathway constitutes a previously unknown probably evolved motion vision encodes salient environmental cues enables animals imitate behaviors as an anticipatory mechanism cope with conditions.

Язык: Английский

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An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice

Neuroscience Bulletin, Год журнала: 2022, Номер 39(5), С. 793 - 807

Опубликована: Дек. 17, 2022

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system warn body of external irritating agents, chronic debilitating but poorly-treated clinical disease leading repetitive scratching and skin lesions. However, neural mechanisms underlying pathophysiology remain mysterious. Here, we identified cell type-dependent role anterior cingulate cortex (ACC) in controlling itch-related excessive behaviors mice. Moreover, delineated circuit originating from excitatory neurons ACC ventral tegmental area (VTA) was critically involved itch. Furthermore, demonstrate ACC→VTA also selectively modulated histaminergic Finally, were shown predominantly innervate non-dopaminergic VTA. Taken together, our findings uncover cortex-midbrain for itch-evoked shed novel insights on therapeutic intervention.

Язык: Английский

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The relationship and clinical significance of serum cytokine expression level and skin pruritus in patients with Hodgkin lymphoma and angioimmunoblastic T-cell lymphoma

International Immunopharmacology, Год журнала: 2024, Номер 131, С. 111777 - 111777

Опубликована: Март 14, 2024

Pruritus of lymphoma is commonly associated with both Hodgkin (HL) and angioimmunoblastic T cell (AITL) critically affects the life quality patient. Recent evidence suggests that pruritogenic cytokines seem to play a significant role in genesis chronic. This study aims investigate itching patients provide basis for potential therapeutic targets. Serum samples were collected from 60 patients, including 47 13 T-cell (AITL), serving as observation group (lymphoma group, LP n = 60). Additionally, serum 8 healthy donors (HD 8) comparison. Within stratified into those pruritus (LWP 30) without (LWOP based on presence skin symptoms. Elevated levels multiple significantly observed comparison HD (p < 0.01). Patients LWP exhibited higher IL-31 0.001), IL-1β (P 0.039), IL-1α 0.037) compared LWOP group. Notably, advanced AITL (stage IV) than early I-Ⅲ, P 0.05). In subgroup analysis, MIG CTACK HL whereas PDGF-BB lower IL-31, IL-1β, are linked lymphoma-associated pruritus. Differences cytokine profiles between subgroups also highlighted. These findings offer valuable insights clinical intervention managing lymphoma-related

Язык: Английский

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Cell Type‐Specific Modulation of Acute Itch Processing in the Anterior Cingulate Cortex

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Сен. 24, 2024

Abstract Despite remarkable progress in understanding the fundamental bases of itching, its cortical mechanisms remain poorly understood. Herein, causal contributions defined anterior cingulate cortex (ACC) neuronal populations to acute itch modulation mice are established. Using cell type‐specific manipulations, opposing functions ACC glutamatergic and GABAergic neurons regulating itching demonstrated. Photometry studies indicated that activated during scratching induced by both histamine chloroquine, whereas activation pattern is complicated subpopulations modalities. By combining type‐ projection‐specific techniques, a thalamocortical circuit further identified from mediodorsal thalamus driving itch‐scratching cycle related histaminergic non‐histaminergic which contingent on postsynaptic parvalbumin‐expressing ACC. These findings reveal cellular signature orchestrating behavioral responses may provide insights into therapies for itch‐related diseases.

Язык: Английский

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Tac1-expressing neurons in the central amygdala predominantly mediate histamine-induced itch by receiving inputs from parabrachial Tac1-expressing neurons

Brain Research, Год журнала: 2025, Номер unknown, С. 149492 - 149492

Опубликована: Фев. 1, 2025

Язык: Английский

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