Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Hereditary sensory and autonomic neuropathies (HSANs) are a group of recessive genetic disorders affecting the sensory and autonomic components of the peripheral nervous system (PNS). Compared with somatosensory dysfunctions, the pathogenesis of visceral dysfunction in HSANs remains understudied. This study investigated the neural circuit mechanisms underlying the arrhythmias observed in conditional Dystonin ( Dst ) gene-trap mice, an animal model of HSAN type VI (HSAN-VI) in which Cre recombinase inactivates Dst expression in selective neural circuits. Inactivation of the Dst gene in PNS neurons using Advillin-Cre caused the degeneration of sensory and sympathetic ganglionic neurons. This was accompanied by arrhythmia, characterized by increased heart rate variability and irregular pulse frequency, which was prominent under isoflurane anesthesia and occurred in the absence of protein aggregate cardiomyopathy. Furthermore, selective inactivation of the Dst gene in PNS sensory neurons using Vglut2-Cre resulted in similar dysregulation of cardiac rhythm. These findings suggest that arrhythmias caused by Dst mutations arise from the disruption of visceral afferent circuits, and that these neural circuits could be potential therapeutic targets for visceral dysfunction in HSAN-VI.

DOI： 10.3389/fncir.2026.1777115

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Publishing type：Research paper (scientific journal)   Publisher：MRE Press  

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have recently emerged as promising targets for the treatment of neuropathic pain. This study investigated the potential involvement of HCN2 channels in the development of trigeminal neuropathic pain following peripheral nerve injury. Infraorbital nerve chronic constriction injury (ION-CCI) model was adopted to rats, and head withdrawal thresholds (HWT) to mechanical stimulation were assessed pre- and postoperatively, as well as after pharmacological intervention. In the trigeminal ganglion (TG), intracellular cyclic adenosine monophosphate (cAMP) and cytoplasmic protein kinase A (PKA) levels were quantified by Enzyme-Linked Immunosorbent Assay (ELISA), while Hcn2 mRNA expression was evaluated by quantitative Polymerase Chain Reaction (qPCR). Immunohistochemical analysis was performed to assess phosphorylated cAMP response element-binding protein (pCREB) expression in the TG and HCN2 expression in infraorbital nerve (ION) axons. In the TG, cAMP and pCREB levels were elevated, whereas cytoplasmic PKA and Hcn2 mRNA levels were reduced. Axonal HCN2 expression was increased in CCI rats. On day 14, HWT was significantly reduced following CCI but was ameliorated by local administration of the HCN channel blocker ivabradine at the site of axonal injury. Collectively, these findings suggest that CCI-induced alterations in cAMP-PKA-pCREB signaling promote HCN2 accumulation in injured axons, thereby contributing to the development of orofacial neuropathic pain following peripheral nerve injury.

DOI： 10.22514/jofph.2026.013

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Language：English   Publishing type：Research paper (scientific journal)  

The nucleus tractus solitarii (NTS) is a brainstem structure that receives information from various internal organs, relaying it to brain networks that regulate emotions and metabolism. Here, we describe a step-by-step experimental protocol for performing minimally invasive in vivo two-photon imaging to record neural population activity in the NTS of anesthetized mice at cellular resolution. This approach is useful for elucidating the neural mechanisms underlying the heterogeneity of NTS neurons. For complete details on the use and execution of this protocol, please refer to Agetsuma et al.1.

DOI： 10.1016/j.xpro.2025.104258

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

Brain-viscera communication is crucial for regulating mental health, with the vagus nerve being a key structure mediating this interaction. Clinically, artificial vagus nerve stimulation (VNS) is used to treat various neuropsychiatric disorders, highlighting the importance of vagal afferent fibers in emotion regulation. The nucleus tractus solitarii (NTS) is a brainstem structure proposed to receive signals from vagal afferents and relay them to brain networks for emotion regulation. However, due to the anatomical complexity and difficulty in accessing the deep-brain NTS region in vivo, its underlying mechanisms remain unclear. Here, we developed a wide-field and deep-brain two-photon imaging method using a double-prism optical interface. This approach enables cellular-resolution imaging to specifically detect NTS neural activity while largely preserving the overlying cerebellum, a region also implicated in emotion regulation. We evaluated NTS neuronal responses to VNS and a gastrointestinal hormone, demonstrating the method's utility for investigating the vagus-NTS pathway in vivo.

DOI： 10.1016/j.crmeth.2025.101010

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

Gene therapy offers great promise in addressing neuropathologies associated with the central and peripheral nervous systems (CNS and PNS). However, genetic access remains difficult, reflecting the critical need for the development of effective and non-invasive gene delivery vectors across species. To that end, we evolved adeno-associated virus serotype 9 (AAV9) capsid in mice and validated two capsids, AAV-MaCPNS1 and AAV-MaCPNS2, across rodent species (mice and rats) and non-human primate (NHP) species (marmosets and rhesus macaques). Intravenous administration of either AAV efficiently transduced the PNS in rodents and both the PNS and CNS in NHPs. Furthermore, we used AAV-MaCPNS1 in mice to systemically deliver the following: (1) the neuronal sensor jGCaMP8s to record calcium signal dynamics in nodose ganglia and (2) the neuronal actuator DREADD to dorsal root ganglia to mediate pain. This conclusively demonstrates the translatability of these two systemic AAVs across four species and their functional utility through proof-of-concept studies in mice.

DOI： 10.1016/j.neuron.2022.05.003

PubMed

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Authorship：Lead author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher：(公財)金原一郎記念医学医療振興財団  

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Authorship：Lead author   Language：Japanese   Publisher：(株)羊土社  

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Authorship：Lead author  

DOI： 10.18958/7011-00003-0000168-00

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Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Authorship：Lead author   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

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Event date： 2025.9

Presentation type：Symposium, workshop panel (public)  

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Event date： 2025.7

Language：English   Presentation type：Symposium, workshop panel (public)  

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Event date： 2024.5

Presentation type：Oral presentation (invited, special)  

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Presentation type：Symposium, workshop panel (public)  

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Language：English   Presentation type：Symposium, workshop panel (public)  

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Type：Competition, symposium, etc. 

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