@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  = {2025},

date = {2025-04-01},

journal = {Heart Rhythm},

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{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 = {2025-04-01},

journal = {Neuron},

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}

}

@article{pmid38277178,

title = {An improved conflict avoidance assay reveals modality-specific differences in pain hypersensitivity across sexes},

author = {Samuel Ferland and Feng Wang and Yves De Koninck and Francesco Ferrini},

doi = {10.1097/j.pain.0000000000003132},

issn = {1872-6623},

year  = {2024},

date = {2024-06-01},

journal = {Pain},

volume = {165},

number = {6},

pages = {1304--1316},

abstract = {Abnormal encoding of somatosensory modalities (ie, mechanical, cold, and heat) are a critical part of pathological pain states. Detailed phenotyping of patients' responses to these modalities have raised hopes that analgesic treatments could one day be tailored to a patient's phenotype. Such precise treatment would require a profound understanding of the underlying mechanisms of specific pain phenotypes at molecular, cellular, and circuitry levels. Although preclinical pain models have helped in that regard, the lack of a unified assay quantifying detailed mechanical, cold, and heat pain responses on the same scale precludes comparing how analgesic compounds act on different sensory phenotypes. The conflict avoidance assay is promising in that regard, but testing conditions require validation for its use with multiple modalities. In this study, we improve upon the conflict avoidance assay to provide a validated and detailed assessment of all 3 modalities within the same animal, in mice. We first optimized testing conditions to minimize the necessary amount of training and to reduce sex differences in performances. We then tested what range of stimuli produce dynamic stimulus-response relationships for different outcome measures in naive mice. We finally used this assay to show that nerve injury produces modality-specific sex differences in pain behavior. Our improved assay opens new avenues to study the basis of modality-specific abnormalities in pain behavior.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38112748,

title = {Assessing spontaneous sensory neuron activity using in vivo calcium imaging},

author = {Sonia Ingram and Kim I Chisholm and Feng Wang and Yves De Koninck and Franziska Denk and George L Goodwin},

doi = {10.1097/j.pain.0000000000003116},

issn = {1872-6623},

year  = {2024},

date = {2024-05-01},

journal = {Pain},

volume = {165},

number = {5},

pages = {1131--1141},

abstract = {Heightened spontaneous activity in sensory neurons is often reported in individuals living with chronic pain. It is possible to study this activity in rodents using electrophysiology, but these experiments require great skill and can be prone to bias. Here, we have examined whether in vivo calcium imaging with GCaMP6s can be used as an alternative approach. We show that spontaneously active calcium transients can be visualised in the fourth lumbar dorsal root ganglion (L4 DRG) through in vivo imaging in a mouse model of inflammatory pain. Application of lidocaine to the nerve, between the inflamed site and the DRG, silenced spontaneous firing and revealed the true baseline level of calcium for spontaneously active neurons. We used these data to train a machine learning algorithm to predict when a neuron is spontaneously active. We show that our algorithm is accurate in 2 different models of pain: intraplantar complete Freund adjuvant and antigen-induced arthritis, with accuracies of 90.0% ±1.2 and 85.9% ±2.1, respectively, assessed against visual inspection by an experienced observer. The algorithm can also detect neuronal activity in imaging experiments generated in a different laboratory using a different microscope configuration (accuracy = 94.0% ±2.2). We conclude that in vivo calcium imaging can be used to assess spontaneous activity in sensory neurons and provide a Google Colaboratory Notebook to allow anyone easy access to our novel analysis tool, for the assessment of spontaneous neuronal activity in their own imaging setups.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38545127,

title = {Understanding the nervous system: lessons from Frontiers in Neurophotonics},

author = {Yves De Koninck and Johanna Alonso and Stéphane Bancelin and Jean-Claude Béïque and Erik Bélanger and Catherine Bouchard and Marco Canossa and Johan Chaniot and Daniel Choquet and Marie-Ève Crochetière and Nanke Cui and Lydia Danglot and Paul De Koninck and Anna Devor and Mathieu Ducros and Angela M Getz and Mohamed Haouat and Iván Coto Hernández and Nate Jowett and Iason Keramidis and Céline Larivière-Loiselle and Flavie Lavoie-Cardinal and Harold D MacGillavry and Asiye Malkoç and Mattia Mancinelli and Pierre Marquet and Steven Minderler and Maxime Moreaud and U Valentin Nägerl and Katerina Papanikolopoulou and Marie-Eve Paquet and Lorenzo Pavesi and David Perrais and Romain Sansonetti and Martin Thunemann and Beatrice Vignoli and Jenny Yau and Clara Zaccaria},

doi = {10.1117/1.NPh.11.1.014415},

issn = {2329-423X},

year  = {2024},

date = {2024-01-01},

journal = {Neurophotonics},

volume = {11},

number = {1},

pages = {014415},

abstract = {The Frontiers in Neurophotonics Symposium is a biennial event that brings together neurobiologists and physicists/engineers who share interest in the development of leading-edge photonics-based approaches to understand and manipulate the nervous system, from its individual molecular components to complex networks in the intact brain. In this Community paper, we highlight several topics that have been featured at the symposium that took place in October 2022 in Québec City, Canada.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38550388,

title = {Special Section Guest Editorial: Frontiers in Neurophotonics},

author = {Yves De Koninck and Paul De Koninck and Anna Devor and Flavie Lavoie-Cardinal},

doi = {10.1117/1.NPh.11.1.014401},

issn = {2329-423X},

year  = {2024},

date = {2024-01-01},

journal = {Neurophotonics},

volume = {11},

number = {1},

pages = {014401},

abstract = {The editorial presents the two-part Special Section on Frontiers in Neurophotonics.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37551444,

title = {Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer's disease mutations},

author = {Iason Keramidis and Brendan B McAllister and Julien Bourbonnais and Feng Wang and Dominique Isabel and Edris Rezaei and Romain Sansonetti and Phil Degagne and Justin P Hamel and Mojtaba Nazari and Samsoon Inayat and Jordan C Dudley and Annie Barbeau and Lionel Froux and Marie-Eve Paquet and Antoine G Godin and Majid H Mohajerani and Yves De Koninck},

doi = {10.1093/brain/awad250},

issn = {1460-2156},

year  = {2023},

date = {2023-12-01},

journal = {Brain},

volume = {146},

number = {12},

pages = {4903--4915},

abstract = {Disinhibition during early stages of Alzheimer's disease is postulated to cause network dysfunction and hyperexcitability leading to cognitive deficits. However, the underlying molecular mechanism remains unknown. Here we show that, in mouse lines carrying Alzheimer's disease-related mutations, a loss of neuronal membrane potassium-chloride cotransporter KCC2, responsible for maintaining the robustness of GABAA-mediated inhibition, occurs pre-symptomatically in the hippocampus and prefrontal cortex. KCC2 downregulation was inversely correlated with the age-dependent increase in amyloid-β 42 (Aβ42). Acute administration of Aβ42 caused a downregulation of membrane KCC2. Loss of KCC2 resulted in impaired chloride homeostasis. Preventing the decrease in KCC2 using long term treatment with CLP290 protected against deterioration of learning and cortical hyperactivity. In addition, restoring KCC2, using short term CLP290 treatment, following the transporter reduction effectively reversed spatial memory deficits and social dysfunction, linking chloride dysregulation with Alzheimer's disease-related cognitive decline. These results reveal KCC2 hypofunction as a viable target for treatment of Alzheimer's disease-related cognitive decline; they confirm target engagement, where the therapeutic intervention takes place, and its effectiveness.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37792939,

title = {Enhanced harm detection following maternal separation: Transgenerational transmission and reversibility by inhaled amiloride},

author = {Marco Battaglia and Orlane Rossignol and Louis-Etienne Lorenzo and Jasmin Deguire and Antoine G Godin and Francesca R D'Amato and Yves De Koninck},

doi = {10.1126/sciadv.adi8750},

issn = {2375-2548},

year  = {2023},

date = {2023-10-01},

journal = {Sci Adv},

volume = {9},

number = {40},

pages = {eadi8750},

abstract = {Early-life adversities are associated with altered defensive responses. Here, we demonstrate that the repeated cross-fostering (RCF) paradigm of early maternal separation is associated with enhancements of distinct homeostatic reactions: hyperventilation in response to hypercapnia and nociceptive sensitivity, among the first generation of RCF-exposed animals, as well as among two successive generations of their normally reared offspring, through matrilineal transmission. Parallel enhancements of acid-sensing ion channel 1 (ASIC1), ASIC2, and ASIC3 messenger RNA transcripts were detected transgenerationally in central neurons, in the medulla oblongata, and in periaqueductal gray matter of RCF-lineage animals. A single, nebulized dose of the ASIC-antagonist amiloride renormalized respiratory and nociceptive responsiveness across the entire RCF lineage. These findings reveal how, following an early-life adversity, a biological memory reducible to a molecular sensor unfolds, shaping adaptation mechanisms over three generations. Our findings are entwined with multiple correlates of human anxiety and pain conditions and suggest nebulized amiloride as a therapeutic avenue.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37362387,

title = {Millimetric scale two-photon Bessel-Gauss beam light sheet microscopy with three-axis isotropic resolution using an axicon lens},

author = {Cléophace Akitegetse and Thomas Charland and Mireille Quémener and Charles Gora and Véronique Rioux and Michel Piché and Yves De Koninck and Martin Lévesque and Daniel C Côté},

doi = {10.1117/1.NPh.10.3.035002},

issn = {2329-423X},

year  = {2023},

date = {2023-07-01},

journal = {Neurophotonics},

volume = {10},

number = {3},

pages = {035002},

abstract = {SIGNIFICANCE: Typical light sheet microscopes suffer from artifacts related to the geometry of the light sheet. One main inconvenience is the non-uniform thickness of the light sheet obtained with a Gaussian laser beam.nnAIM: We developed a two-photon light sheet microscope that takes advantage of a thin and long Bessel-Gauss beam illumination to increase the sheet extent without compromising the resolution.nnAPPROACH: We use an axicon lens placed directly at the output of an amplified femtosecond laser to produce a long Bessel-Gauss beam on the sample. We studied the dopaminergic system and its projections in a whole cleared mouse brain.nnRESULTS: Our light sheet microscope allows an isotropic resolution of  in all three axes of the scanned volume while keeping a millimetric-sized field of view, and a fast acquisition rate of up to . With slight modifications to the optical setup, the sheet extent can be increased to 6 mm.nnCONCLUSION: The proposed system's sheet extent and resolution surpass currently available systems, enabling the fast imaging of large specimens.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37475396,

title = {Improving flat fluorescence microscopy in scattering tissue through deep learning strategies},

author = {Mohamad Feshki and Sylvain Martel and Yves De Koninck and Benoit Gosselin},

doi = {10.1364/OE.489677},

issn = {1094-4087},

year  = {2023},

date = {2023-07-01},

journal = {Opt Express},

volume = {31},

number = {14},

pages = {23008--23026},

abstract = {Intravital microscopy in small animals growingly contributes to the visualization of short- and long-term mammalian biological processes. Miniaturized fluorescence microscopy has revolutionized the observation of live animals' neural circuits. The technology's ability to further miniaturize to improve freely moving experimental settings is limited by its standard lens-based layout. Typical miniature microscope designs contain a stack of heavy and bulky optical components adjusted at relatively long distances. Computational lensless microscopy can overcome this limitation by replacing the lenses with a simple thin mask. Among other critical applications, Flat Fluorescence Microscope (FFM) holds promise to allow for real-time brain circuits imaging in freely moving animals, but recent research reports show that the quality needs to be improved, compared with imaging in clear tissue, for instance. Although promising results were reported with mask-based fluorescence microscopes in clear tissues, the impact of light scattering in biological tissue remains a major challenge. The outstanding performance of deep learning (DL) networks in computational flat cameras and imaging through scattering media studies motivates the development of deep learning models for FFMs. Our holistic ray-tracing and Monte Carlo FFM computational model assisted us in evaluating deep scattering medium imaging with DL techniques. We demonstrate that physics-based DL models combined with the classical reconstruction technique of the alternating direction method of multipliers (ADMM) perform a fast and robust image reconstruction, particularly in the scattering medium. The structural similarity indexes of the reconstructed images in scattering media recordings were increased by up to 20% compared with the prevalent iterative models. We also introduce and discuss the challenges of DL approaches for FFMs under physics-informed supervised and unsupervised learning.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}