Central medial thalamic nucleus dynamically participates in acute itch sensation and chronic itch-induced anxiety-like behavior in male mice

Li, Jiani; Wu, Xuemei; Zhao, Liu-Jie; Sun, Han-Xue; Hong, Jie; Wu, Feng-Ling; Chen, Sihai; Chen, Tao; Li, Hui; Dong, Yu-Lin; Li, Yun-Qing

doi:10.1038/s41467-023-38264-4

Cited by 20 publications

(3 citation statements)

References 58 publications

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“…Thus, a multi-synaptic neural circuit between the spinal cord, PBN, and RVM is instrumental in driving and modulating pain thresholds and simultaneously suppressing itch-induced scratching. The PBN Tacr1 neurons project to the central thalamus and may mediate the affective-motivational components of itch through this connection (Li et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

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

Prajapati,

Shah,

Barik

2024

Preprint

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Pain and itch are unpleasant and distinct sensations that give rise to behaviors such as reflexive withdrawal and scratching in humans and mice. Interestingly, it has been observed that pain modulate itch through the neural circuits housed in the brain and spinal cord. However, we are yet to fully understand the identities of and mechanisms by which specific neural circuits mediate pain-induced modulation of itch. Independent studies indicate that brainstem nuclei such as the lateral parabrachial nucleus (LPBN) and rostral ventromedial medulla (RVM) are important for the suppression of itch by painful stimuli. Here, using mouse and viral genetics, rabies tracing, chemogenetics, and calcium imaging, we show that the synaptic connections between LPBN and RVM plays an instrumental role in the interactions between pain and itch. Notably, we found that the LPBN neurons that express the gene encoding the substance P receptor, Tacr1 (LPBNTacr1), synapse onto Tacr1-expressing RVM neurons (RVMTacr1). The RVMTacr1neurons were found to be nociceptive, sufficient for inhibiting itch, and necessary for pain-induced itch suppression. Moreover, through brain-wide anterograde and retrograde viral tracing studies, we found that the RVMTacr1neurons are bidirectionally connected with LPBN, periaqueductal gray (PAG), and lateral hypothalamic area (LHA). Thus, together, our data indicate that the RVMTacr1neurons integrate nociceptive information to mediate itch-induced scratching and can mediate the physiological effects of itch through their downstream targets.

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Section: Discussionmentioning

confidence: 99%

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

Prajapati,

Shah,

Barik

2024

Preprint

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“…Fluorescence in situ hybridization (FISH) staining was performed according to the procedures described in previous studies [23]. Tac1-Ai9 mice were perfused and sectioned with enzymes-free throughout the experiments.…”

Section: Fluorescence In Situ Hybridizationmentioning

confidence: 99%

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

Zhang,

Shi,

Mao

et al. 2024

Preprint

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Itch is a distinct and bothersome sensation closely associated with a strong urge to scratch. Both the parabrachial nucleus (PBN) and the central amygdala (CeA) are responsive to itch stimuli and contain neurons that express tachykinin 1 (Tac1), which are known for their significant involvement in itch-induced scratching at both spinal and supraspinal levels. Significantly, the PBN neurons project their axons to form close connections with the CeA neurons. However, the role of the PBNTac1-CeATac1 pathway in modulating itch remains to be determined. We utilized immunohistochemistry, fiber photometry, chemogenetic, and behavioral techniques to investigate the role of the PBNTac1-CeATac1 pathway in itch. Our results indicate that neurons in the CeA can be more activated by acute itch than chronic itch. Notably, in response to acute itch stimuli, both CeATac1 and PBNTac1 neurons are specifically activated by histamine (His)-induced itch. Furthermore, the Tac1-positive terminals from the PBNTac1 neurons formed close connections with CeATac1 neurons. We also demonstrated that activating the PBN-CeA pathway using a chemogenetic approach could increase scratching behaviors in His-induced itch, other than chloroquine (CQ)-induced itch. Conversely, inhibiting the PBN-CeA pathway decreased scratching behaviors in mice with His-induced itch. Taken together, these results suggest that the PBNTac1-CeATac1 pathway may play a specific role in modulating His-induced acute itch.

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“…The parabrachial nucleus (PBN), being located within the pons, functions as an integrator of sensory input from the surrounding environment and subsequently relays this information to forebrain structures. The majority of PBN neurons are Ivyspring International Publisher excitatory features [4,5], being positively correlated with behaviors indicative of pain [6][7][8], itch [9,10], fear [11], aversive [12], and emotion [10,13]. Our recent research has identified a specific subpopulation of choline acetyltransferase (ChAT + ) neurons located in the PBN, specifically within the external lateral portion of PBN (eLPB ChAT ) [14].…”

Section: Introductionmentioning

confidence: 99%

Distinct eLPB^ChAT projections for methamphetamine withdrawal anxiety and primed reinstatement of conditioned place preference

Chen,

Guo,

Zhou

et al. 2024

Theranostics

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Methamphetamine (METH) withdrawal anxiety symptom and relapse have been significant challenges for clinical practice, however, the underlying neuronal basis remains unclear. Our recent research has identified a specific subpopulation of choline acetyltransferase (ChAT + ) neurons localized in the external lateral portion of parabrachial nucleus (eLPB ChAT ), which modulates METH primed-reinstatement of conditioned place preference (CPP). Here, the anatomical structures and functional roles of eLPB ChAT projections in METH withdrawal anxiety and primed reinstatement were further explored. Methods: In the present study, a multifaceted approach was employed to dissect the LPB ChAT+ projections in male mice, including anterograde and retrograde tracing, acetylcholine (Ach) indicator combined with fiber photometry recording, photogenetic and chemogenetic regulation, as well as electrophysiological recording. METH withdrawal anxiety-like behaviors and METH-primed reinstatement of conditioned place preference (CPP) were assessed in male mice. Results: We identified that eLPB ChAT send projections to PKCδ-positive (PKCδ + ) neurons in lateral portion of central nucleus of amygdala (lCeA PKCδ ) and oval portion of bed nucleus of the stria terminalis (ovBNST PKCδ ), forming eLPB ChAT -lCeA PKCδ and eLPB ChAT -ovBNST PKCδ pathways. At least in part, the eLPB ChAT neurons positively innervate lCeA PKCδ neurons and ovBNST PKCδ neurons through regulating synaptic elements of presynaptic Ach release and postsynaptic nicotinic acetylcholine receptors (nAChRs). METH withdrawal anxiety and METH-primed reinstatement of CPP respectively recruit eLPB ChAT -lCeA PKCδ pathway and eLPB ChAT -ovBNST PKCδ pathway in male mice. Conclusion: Our findings put new insights into the complex neural networks, especially focusing on the eLPB ChAT projections. The eLPB ChAT is a critical node in the neural networks governing METH withdrawal anxiety and primed-reinstatement of CPP through its projections to the lCeA PKCδ and ovBNST PKCδ , respectively.

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Central medial thalamic nucleus dynamically participates in acute itch sensation and chronic itch-induced anxiety-like behavior in male mice

Cited by 20 publications

References 58 publications

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

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

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

Distinct eLPB^ChAT projections for methamphetamine withdrawal anxiety and primed reinstatement of conditioned place preference

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Central medial thalamic nucleus dynamically participates in acute itch sensation and chronic itch-induced anxiety-like behavior in male mice

Cited by 20 publications

References 58 publications

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

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

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

Distinct eLPBChAT projections for methamphetamine withdrawal anxiety and primed reinstatement of conditioned place preference

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Distinct eLPB^ChAT projections for methamphetamine withdrawal anxiety and primed reinstatement of conditioned place preference