@article{pmid42706254,

title = {Deterministic wet etching of aspheric fiber microlenses with tunable conic geometry for tailored optical functionality},

author = {Sanggon Kim and Iason Keramidis and Isabel Plasencia-Fernandez and Johanna Alonso and Louison Brochoire and Cyril Bories and Annie Barbeau and Younes Messaddeq and Yves De Koninck},

doi = {10.1038/s41467-026-75331-y},

issn = {2041-1723},

year  = {2026},

date = {2026-08-01},

journal = {Nat Commun},

volume = {17},

number = {1},

abstract = {Efficient coupling between guided optical fiber modes and radiated fields in the surrounding medium remains a fundamental limitation across photonics, sensing, and biophotonics. Micro-lensed fibers offer a promising solution, yet scalable fabrication with predictable geometry and deterministic optical performance has remained elusive. Here, we introduce laser-controlled wet-chemical etching (LCWCE), a single-parameter strategy that directly sculpts micro-lenses, from hyperbolic to parabolic and prolate elliptical profiles, on standard optical fibers. Local laser illumination establishes an axially confined etching-rate gradient, enabling sub-micrometer control of curvature and working distance independent of fiber type or internal structure. A physics-separated multiphysics framework combining wave optics, heat-transfer, and temperature-dependent etching kinetics captures the observed geometry evolution and validates the underlying mechanism. LCWCE enables milliwatt-scale, minimal-power fiber-based optical trapping, as well as minimally invasive in vivo dendritic detection and single-cell neural interrogation beyond 1.5 mm depth in live brains, transforming ubiquitous optical fibers into scalable, high-performance photonic probes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42173713,

title = {Nucleus raphe magnus serotonin neurones bidirectionally control spinal nociceptive transmission in mice},

author = {Zoé Grivet and Aude Verboven and Franck Aby and Rabia Bouali-Benazzouz and Thibault Dhellemmes and Emma Perrot and Anna Beyeler and Lora K Heisler and Maddalena Balia and Arne Battefeld and Hugo Martin and Aude Retailleau and François Maingret and Xavier Fioramonti and Marc Landry and Yves De Koninck and Abdelhamid Benazzouz and Pascal Fossat},

doi = {10.1016/j.bja.2026.03.069},

issn = {1471-6771},

year  = {2026},

date = {2026-07-01},

journal = {Br J Anaesth},

volume = {137},

number = {1},

pages = {193--209},

abstract = {BACKGROUND: Noxious stimuli are conveyed to and integrated in the dorsal horn of the spinal cord before being transmitted to supraspinal centres, where pain perception is generated. Descending pathways from the brainstem dynamically modulate this integration, either facilitating or inhibiting nociceptive information based on physiological, emotional, genetic and environmental factors. Serotonergic neurones in the nucleus raphe magnus (NRM), activating different spinal 5-hydroxytryptamine (5-HT) receptors, exert bidirectional control, both facilitatory and inhibitory, but the underlying mechanisms of this control remain unclear.nnMETHODS: Serotonergic modulation by the NRM of nociception was investigated in adult mice using imaging, behavioural, pharmacological, electrophysiological, chemogenetic and optogenetic approaches.nnRESULTS: The action of serotonergic neurones in the NRM on spinal nociceptive transmission depends on their activation pattern, which targets different spinal 5-HT receptors likely associated with different spinal microcircuits. Serotonergic neurones of the NRM exert a tonic analgesic effect mediated by 5-HT receptor. Low increases in 5-HT activity led to increased analgesia through spinal inhibitory interneurones expressing 5-HT and 5-HT receptors. Prolonged stimulation of serotonergic neurones led to hyperalgesia mediated by 5-HT receptors. Comparison of 5-HT receptors in spinal tissue from mice and humans shows that 5-HT receptors have high expression level, comparable between both species.nnCONCLUSIONS: These results propose a bidirectional model of action by serotonin neurones of nociceptive transmission depending on their level of activity and show that 5-HT receptors mediate the serotonin-induced analgesia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42242217,

title = {A specialized population of hair afferents dedicated to transmitting mechanical itch},

author = {Mahar Fatima and Hankyu Lee and Hwayeon Cha and Chia Chun Hor and Feng Wang and Jingyi Liu and Jonathan Damblon and Wenwen Zhang and Katie Qu and Yumena Nagai and Abbey Dinh and Ziyan Wu and Ranveer Ajimal and Ailin Emily Xiong and Madeleine Chai and Alyssa Asmar and Wei Cai and Xiaowei Zhou and Anuraag Balaji and Haili Pan and Lorraine Horwitz and Lam C Tsoi and Hongzhen Hu and X Z Shawn Xu and Yves De Koninck and Bo Duan},

doi = {10.1016/j.neuron.2026.05.017},

issn = {1097-4199},

year  = {2026},

date = {2026-06-01},

journal = {Neuron},

abstract = {Hairs serve as sensory structures that are crucial for perceiving environmental cues through interactions with sensory endings. Depigmented and demedullated atypical hairs exhibit a limited distribution on mammalian skin and have not been extensively studied. In this study, we identify a specific type of hair, termed vellus-like hairs (VLHs), which are enriched in the postauricular region and on the hindpaws of mice. These hairs are innervated by Aβ low-threshold mechanoreceptors (LTMRs) that co-express Toll-like receptor 5 and Calbindin1 (TLR5). Genetic ablation or silencing of these hair afferents eliminated mechanical itch generated by gentle VLH stroking or indentation under both physiological and pathological conditions. Conversely, optogenetic activation of TLR5 hair afferents evoked itch behaviors. Mechanosensitive Piezo2 channels in TLR5 Aβ-LTMRs function as key mechanotransducers for mechanical itch signaling. Our study sheds light on the previously poorly understood somatosensory physiology of unique hairs, emphasizing the significant role of TLR5 Aβ-LTMRs in itch transmission.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41962851,

title = {Excessive inhibition in the medial prefrontal cortex contributes to cognitive susceptibility in aging},

author = {Iason Keramidis and Patrick Desrosiers and Andrée-Anne Verreault and Romain Sansonetti and Reza Hazrati and Antoine G Godin and Yves De Koninck},

doi = {10.1016/j.nbd.2026.107385},

issn = {1095-953X},

year  = {2026},

date = {2026-06-01},

journal = {Neurobiol Dis},

volume = {224},

pages = {107385},

abstract = {Aging is the most impactful risk factor for cognitive decline. The prefrontal cortex (PFC), a brain region essential for higher-order cognition, undergoes age-related synaptic alterations which are postulated to yield an excitation/inhibition imbalance within the PFC. Here, we assessed cognitive performance in young and aged mice using a battery of behavioral tests linked to PFC function. Behavioral variability within the aged cohort suggested structured heterogeneity in cognitive performance. Using a data-driven analytical framework integrating behavioral dimensionality reduction, consensus clustering, and spectral embedding we achieved robust and stable behavioral subgroup separation within the aged population. This approach revealed a subset of "cognitively susceptible" aged mice with pronounced memory and novelty-directed exploration deficits, distinct from both "resilient" aged mice and young controls. Unlike resilient aged mice, susceptible mice showed intact social preference. Susceptible aged mice exhibited elevated levels of the inhibitory synaptic proteins Gephyrin and VGAT in the PFC, a pattern absent in resilient aged mice. Notably, the increase in Gephyrin was accounted for by a higher density of inhibitory synapses, indicating a structural shift toward inhibition. Consistent with this mechanism, optogenetically enhancing inhibition in the PFC of young mice was sufficient to recapitulate the memory and novelty-exploration deficits observed in susceptible aged mice. Altogether, these findings implicate excessive prefrontal inhibition as a mechanistic substrate contributing to cognitive susceptibility in unsuccessful aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41619726,

title = {Runx1 transcription factor modulates opioid analgesia and withdrawal in humans and rodents},

author = {Heather Leduc-Pessah and Brendan B McAllister and Sarthak Sinha and Sierra Stokes-Heck and Daisuke Nishizawa and Churmy Y Fan and Marie-Kim St-Pierre and Amyaouch Bradaia and Manon Defaye and Nicole E Burma and Jonathan Damblon and Einer Muñoz-Pino and Frank Visser and Marie-France Dorion and Luke M Healy and Ye Man Tang and Julia Canet-Pons and Nynke J van den Hoogen and Zizhen Zhang and Flavia T T Antunes and Valerio E C Piscopo and Margaret Medina and Ken-Ichi Fukuda and Tatsuya Ichinohe and Makoto Nagashima and Masakazu Hayashida and Emma Johnson and Arpana Agrawal and Louisa Degenhardt and Nicholas G Martin and Gerald W Zamponi and Elliot C Nelson and Christophe Altier and Marie-Eve Tremblay and Chad Bousman and Stefano Stifani and Yves De Koninck and Kazutaka Ikeda and Jeff Biernaskie and Tuan Trang},

doi = {10.1016/j.neuron.2025.11.018},

issn = {1097-4199},

year  = {2026},

date = {2026-03-01},

journal = {Neuron},

volume = {114},

number = {5},

pages = {903--921.e13},

abstract = {Opioid analgesia and adverse outcomes vary across individuals. We show that runt-related transcription factor 1 (Runx1) modulates the microglial transcriptome and is a genetic determinant of opioid antinociceptive responses and withdrawal. In mice, Runx1 deletion in microglia produces distinct ultrastructural and transcriptomic signatures, reducing morphine potency despite no prior opioid exposure. These mice also require greater post-operative morphine and display exacerbated morphine-induced hyperalgesia and withdrawal. Single-cell RNA sequencing (scRNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analyses reveal a unique microglial state, with Runx1 regulating inflammatory signaling and key microglial functions. In humans, association analyses link RUNX1 variants to inter-individual differences in perioperative opioid requirement and withdrawal severity. Identifying RUNX1 susceptibility genotypes may be important for understanding individual variability in opioid responses, with potential relevance for future personalized approaches.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40221111,

title = {Excitability properties of cardiac calbindin neurons: Identifying a unique neuronal population},

author = {Guénaëlle Lizot and Jocelyn Bescond and Yves De Koninck and Mohamed Chahine and Patrick Bois and Jean-François Faivre and Aurélien Chatelier},

doi = {10.1016/j.hrthm.2025.04.007},

issn = {1556-3871},

year  = {2026},

date = {2026-03-01},

journal = {Heart Rhythm},

volume = {23},

number = {3},

pages = {741--750},

abstract = {BACKGROUND: The intrinsic cardiac nervous system is a complex system that plays a critical role in the regulation of cardiac physiologic parameters and has been shown to contribute to cardiac arrhythmias. To date, several types of neurons with distinct neurochemical and electrophysiologic phenotypes have been identified. However, no study has correlated the neurochemical phenotype to a specific electrophysiologic behavior. Calbindin-D28k, a calcium-binding protein, is expressed in numerous cardiac neurons.nnOBJECTIVE: Given that changes in neuronal excitability have been associated with arrhythmia susceptibility and that calbindin expression has been associated with modulations of neuronal excitability, our objective was to assess whether the cardiac calbindin neuronal population has specific properties that could be involved in cardiac regulation and arrhythmias.nnMETHODS: By using a Cre-Lox mouse model to specifically target calbindin neurons with a fluorescent reporter, we characterized the neurochemical and electrophysiologic phenotype of this cardiac neuronal population.nnRESULTS: Calbindin neurons exhibit a specific neurochemical expression profile and a larger soma with shorter neurite length compared with other neurons. This was combined with a distinct electrophysiologic signature characterized by a lower excitability with a predominantly phasic profile associated to a lower N-type calcium current density.nnCONCLUSION: Calbindin cardiac neurons display distinct neurochemical, morphologic, and electrophysiologic properties, resembling the cardiac neuronal remodeling observed in pathologic processes such as heart failure. Therefore, we believe that this specific neuronal population deserves investigation in the context of cardiac diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41461929,

title = {Recommendations for the inclusion and study of sex and gender in research},

author = {David P Finn and Brian E McGuire and Simon Beggs and Katelynn E Boerner and Karen D Davis and Ruth Defrin and Yves De Koninck and Hemakumar Devan and Ryan Donovan and Eleonora Fetter and Herta Flor and Brona M Fullen and Catherine R Healy and Edmund Keogh and Rohini Kuner and Miriam Kunz and Rebecca M Lane and Stefan Lautenbacher and Emeran A Mayer and Jeffrey S Mogil and Siobhain M O'Mahony and Kieran O'Sullivan and Louise Riordan and Michael W Salter and Francesco Scarlatti and George Shorten and Kathleen A Sluka and Jennifer N Stinson and Kevin E Vowles and Suellen M Walker and Ipek Yalcin and Michelle Roche},

doi = {10.1038/s41593-025-02164-1},

issn = {1546-1726},

year  = {2026},

date = {2026-02-01},

journal = {Nat Neurosci},

volume = {29},

number = {2},

pages = {256--266},

abstract = {Sex and gender are important variables in research, but they are inconsistently explored. The international PAINDIFF Network makes 13 recommendations for studying sex and gender as variables in pain research, which are applicable across the spectrum of biopsychosocial research. Five universal recommendations apply to the majority of research studies: (1) include males and females as standard practice, (2) account for sex in randomization or counterbalancing and testing order, (3) power for sex differences when sex is a primary experimental variable, (4) include detailed reporting of experimental design, and (5) conduct sex-disaggregated analysis and reporting. Three additional recommendations specifically for preclinical studies and five additional recommendations for human and clinical studies are included. Recommendations for stakeholders, such as editors, reviewers, funding bodies and policymakers, have also been developed. Wide adoption and implementation of these recommendations will reduce variability, improve reproducibility and enhance the translatability of research findings within and beyond the field of pain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40667986,

title = {Decreased KCC2 expression in the human spinal dorsal horn associated with chronic pain and long-term opioid use},

author = {Olivia C Davis and Samuel Ferland and Louis-Etienne Lorenzo and Clare Murray-Lawson and Stephanie Shiers and Muhammad Saad Yousuf and Annemarie Dedek and Eve C Tsai and Erin Vines and Peter Horton and Anna Cervantes and Tariq Khan and Geoffrey Funk and Gregory Dussor and Antoine G Godin and Francesco Ferrini and Yves De Koninck and Michael E Hildebrand and Theodore J Price},

doi = {10.1097/j.pain.0000000000003700},

issn = {1872-6623},

year  = {2025},

date = {2025-11-01},

journal = {Pain},

volume = {166},

number = {11},

pages = {e665--e673},

abstract = {Loss of GABAergic and glycinergic inhibitory efficacy in the spinal dorsal horn is associated with neuropathic pain and opioid-induced hyperalgesia in rodent models. Downregulation of the KCC2 chloride extrusion transporter is a key mechanism underlying this decreased inhibitory efficacy, but to-date there is no evidence supporting or opposing this hypothesis in humans. Here, we demonstrate that KCC2 expression is decreased in superficial dorsal horn neurons of organ donors who died with a documented history of pain, or of long-term opioid use. We show profoundly decreased KCC2 dorsal horn membrane expression in a primary cohort associated with either chronic pain or opioid use, and in a replication cohort of mixed chronic pain and opioid use history. These results show that decreased dorsal horn inhibitory efficacy likely promotes chronic pain in humans and support the development of therapeutics augmenting KCC2 function as a treatment for chronic pain and opioid use disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41169497,

title = {Chronic optogenetic activation of hippocampal CA1 neurons triggers Alzheimer's disease-like proteomic remodeling},

author = {Iason Keramidis and Martina Samiotaki and Romain Sansonetti and Johanna Alonso and Patrick Desrosiers and Katerina Papanikolopoulou and Yves De Koninck},

doi = {10.1016/j.isci.2025.113454},

issn = {2589-0042},

year  = {2025},

date = {2025-10-01},

journal = {iScience},

volume = {28},

number = {10},

pages = {113454},

abstract = {Neuronal overexcitability triggers synaptic changes, leading to neural hyperactivity, network disruption, and is postulated to trigger neurodegeneration in Alzheimer's disease (AD). However, the sequence of synaptic changes from excessive activity remains unclear. We employed optogenetics to induce sustained neuronal hyperactivity in the hippocampi of wild-type and AD-like 5xFAD mice. After a month of daily optogenetic stimulation, the proteomic profiles of photoactivated wild-type and 5xFAD mice exhibited remarkable similarity. Proteins involved in translation, protein transport, autophagy, and notably in the AD pathology were upregulated in wild-type mice. Conversely, both glutamatergic and GABAergic synaptic proteins were downregulated. These hippocampal proteomic and signaling alterations in wild-type mice resulted in spatial memory loss and augmented Αβ42 secretion. Collectively, these findings indicate that sustained neuronal hyperactivity alone replicates proteome changes seen in AD-like mutant mice. Therefore, prolonged neuronal hyperactivity may contribute to synaptic transmission disruption, memory deficits and the neurodegenerative process associated with AD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40280127,

title = {The gut microbiota promotes pain in fibromyalgia},

author = {Weihua Cai and May Haddad and Rana Haddad and Inbar Kesten and Tseela Hoffman and Reut Laan and Susan Westfall and Manon Defaye and Nasser S Abdullah and Calvin Wong and Nicole Brown and Shannon Tansley and Kevin C Lister and Mehdi Hooshmandi and Feng Wang and Louis-Etienne Lorenzo and Volodya Hovhannisyan and David Ho-Tieng and Vibhu Kumar and Behrang Sharif and Bavanitha Thurairajah and Jonathan Fan and Tali Sahar and Charlotte Clayton and Neil Wu and Ji Zhang and Haggai Bar-Yoseph and Milena Pitashny and Emerson Krock and Jeffrey S Mogil and Masha Prager-Khoutorsky and Philippe Séguéla and Christophe Altier and Irah L King and Yves De Koninck and Nicholas J B Brereton and Emmanuel Gonzalez and Yoram Shir and Amir Minerbi and Arkady Khoutorsky},

doi = {10.1016/j.neuron.2025.03.032},

issn = {1097-4199},

year  = {2025},

date = {2025-07-01},

journal = {Neuron},

volume = {113},

number = {13},

pages = {2161--2175.e13},

abstract = {Fibromyalgia is a prevalent syndrome characterized by widespread pain in the absence of evident tissue injury or pathology, making it one of the most mysterious chronic pain conditions. The composition of the gut microbiota in individuals with fibromyalgia differs from that of healthy controls, but its functional role in the syndrome is unknown. Here, we show that fecal microbiota transplantation from fibromyalgia patients, but not from healthy controls, into germ-free mice induces pain and numerous molecular phenotypes that parallel known changes in fibromyalgia patients, including immune activation and metabolomic profile alterations. Replacing the fibromyalgia microbiota with a healthy microbiota substantially alleviated pain in mice. An open-label trial in women with fibromyalgia (Registry MOH_2021-11-04_010374) showed that transplantation of a healthy microbiota is associated with reduced pain and improved quality of life. We conclude that altered gut microbiota has a role in fibromyalgia pain, highlighting it as a promising target for therapeutic interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}