@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{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{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{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{pmid38082985,

title = {Deep Learning Empowered Fresnel-based Lensless Fluorescence Microscopy},

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

doi = {10.1109/EMBC40787.2023.10339990},

issn = {2694-0604},

year  = {2023},

date = {2023-07-01},

journal = {Annu Int Conf IEEE Eng Med Biol Soc},

volume = {2023},

pages = {1--4},

abstract = {Miniaturized fluorescence microscopy has revolutionized the way neuroscientists study the brain in-vivo. Recent developments in computational lensless imaging promise a next generation of miniaturized microscopes in lensless fluorescence microscopy. We developed a microscope prototype using an optimized Fresnel amplitude mask. While many lensless imaging modalities have reported excellent performance using Deep Learning (DL) approaches, DL application in fluorescence imaging has been left untouched. We generated a computational dataset based on experimental system calibration to evaluate DL capabilities on biological cell morphologies. We show that our DL-assisted microscope can provide high-quality imaging with a structural similarity index of 89%. The least absolute error was decreased by 63% using the DL-assisted method compared with the classical models. The state-of-the-art performance of this prototype enhances the expected potential of amplitude masks in lensless microscopy applications, which are critical for robust in-vivo flat microscopy with engineered image sensors.Clinical Relevance- This study aids in advancing miniaturized fluorescence microscopy, which greatly impacts long-term brain circuit and disease studies in freely moving animal models.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34847973,

title = {An Indigenous Lens on Priorities for the Canadian Brain Research Strategy},

author = {Melissa L Perreault and Malcolm King and Chelsea Gabel and Christopher J Mushquash and Yves De Koninck and Ashley Lawson and Caterina Marra and Caroline Ménard and Jennie Z Young and Judy Illes},

doi = {10.1017/cjn.2021.501},

issn = {0317-1671},

year  = {2023},

date = {2023-01-01},

journal = {Can J Neurol Sci},

volume = {50},

number = {1},

pages = {96--98},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36656715,

title = {Time-dependent and selective microglia-mediated removal of spinal synapses in neuropathic pain},

author = {Noosha Yousefpour and Samantha Locke and Haley Deamond and Chengyang Wang and Lucas Marques and Manon St-Louis and Johanne Ouellette and Arkady Khoutorsky and Yves De Koninck and Alfredo Ribeiro-da-Silva},

doi = {10.1016/j.celrep.2023.112010},

issn = {2211-1247},

year  = {2023},

date = {2023-01-01},

journal = {Cell Rep},

volume = {42},

number = {1},

pages = {112010},

abstract = {Neuropathic pain is a debilitating condition resulting from damage to the nervous system. Imbalance of spinal excitation and inhibition has been proposed to contribute to neuropathic pain. However, the structural basis of this imbalance remains unknown. Using a preclinical model of neuropathic pain, we show that microglia selectively engulf spinal synapses that are formed by central neurons and spare those of peripheral sensory neurons. Furthermore, we reveal that removal of inhibitory and excitatory synapses exhibits distinct temporal patterns, in which microglia-mediated inhibitory synapse removal precedes excitatory synapse removal. We also find selective and gradual increase in complement depositions on dorsal horn synapses that corresponds to the temporal pattern of microglial synapse pruning activity and type-specific synapse loss. Together, these results define a specific role for microglia in the progression of neuropathic pain pathogenesis and implicate these immune cells in structural remodeling of dorsal horn circuitry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34363210,

title = {Remote local photoactivation of morphine produces analgesia without opioid-related adverse effects},

author = {Marc López-Cano and Joan Font and Ester Aso and Kristoffer Sahlholm and Gisela Cabré and Jesús Giraldo and Yves De Koninck and Jordi Hernando and Amadeu Llebaria and Víctor Fernández-Dueñas and Francisco Ciruela},

doi = {10.1111/bph.15645},

issn = {1476-5381},

year  = {2023},

date = {2023-04-01},

journal = {Br J Pharmacol},

volume = {180},

number = {7},

pages = {958--974},

abstract = {BACKGROUND AND PURPOSE: Opioid-based drugs are the gold standard medicines for pain relief. However, tolerance and several side effects (i.e. constipation and dependence) may occur upon chronic opioid administration. Photopharmacology is a promising approach to improve the benefit/risk profiles of these drugs. Thus, opioids can be locally activated with high spatiotemporal resolution, potentially minimizing systemic-mediated adverse effects. Here, we aimed at developing a morphine photo-derivative (photocaged morphine), which can be activated upon light irradiation both in vitro and in vivo.nnEXPERIMENTAL APPROACH: Light-dependent activity of pc-morphine was assessed in cell-based assays (intracellular calcium accumulation and electrophysiology) and in mice (formalin animal model of pain). In addition, tolerance, constipation and dependence were investigated in vivo using experimental paradigms.nnKEY RESULTS: In mice, pc-morphine was able to elicit antinociceptive effects, both using external light-irradiation (hind paw) and spinal cord implanted fibre-optics. In addition, remote morphine photoactivation was devoid of common systemic opioid-related undesired effects, namely, constipation, tolerance to the analgesic effects, rewarding effects and naloxone-induced withdrawal.nnCONCLUSION AND IMPLICATIONS: Light-dependent opioid-based drugs may allow effective analgesia without the occurrence of tolerance or the associated and severe opioid-related undesired effects.nnLINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.},

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{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{pmid37171242,

title = {We need to talk: The urgent conversation on chronic pain, mental health, prescribing patterns and the opioid crisis},

author = {Marco Battaglia and Cornelius B Groenewald and Fiona Campbell and Simona Scaini and Yves De Koninck and Jennifer Stinson and Patrick D Quinn},

doi = {10.1177/02698811221144635},

issn = {1461-7285},

year  = {2023},

date = {2023-05-01},

journal = {J Psychopharmacol},

volume = {37},

number = {5},

pages = {437--448},

abstract = {The opioid crisis' pathways from first exposure onwards to eventual illnesses and fatalities are multiple, intertwined and difficult to dissect. Here, we offer a multidisciplinary appraisal of the relationships among mental health, chronic pain, prescribing patterns worldwide and the opioid crisis. Because the opioid crisis' toll is especially harsh on young people, emphasis is given on data regarding the younger strata of the population. Because analgesic opioid prescription constitute a recognised entry point towards misuse, opioid use disorder, and ultimately overdose, prescribing patterns across different countries are examined as a modifiable hazard factor along these pathways of risk. Psychiatrists are called to play a more compelling role in this urgent conversation, as they are uniquely placed to provide synthesis and lead action among the different fields of knowledge and care that lie at the crossroads of the opioid crisis. Psychiatrists are also ideally positioned to gauge and disseminate the foundations for diagnosis and clinical management of mental conditions associated with chronic pain, including the identification of hazardous and protective factors. It is our hope to spark more interdisciplinary exchanges and encourage psychiatrists worldwide to become leaders in an urgent conversation with interlocutors from the clinical and basic sciences, policy makers and stakeholders including clients and their families.},

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}

}

@article{pmid36220871,

title = {A novel assessment of fine-motor function reveals early hindlimb and detectable forelimb deficits in an experimental model of ALS},

author = {C Sahara Khademullah and Yves De Koninck},

doi = {10.1038/s41598-022-20333-1},

issn = {2045-2322},

year  = {2022},

date = {2022-10-01},

journal = {Sci Rep},

volume = {12},

number = {1},

pages = {17010},

abstract = {Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated with the loss of cortical and spinal motor neurons (MNs) and muscle degeneration (Kiernan et al. in Lancet 377:942-955, 2011). In the preclinical setting, functional tests that can detect early changes in motor function in rodent models of ALS are critical to understanding the etiology of the disease and treatment development. Here, we established a string-pulling paradigm that can detect forelimb and hindlimb motor deficits in the SOD1 mouse model of ALS earlier than traditional motor performance tasks. Additionally, our findings indicate that early loss of forelimb and hindlimb function is correlated with cortical and spinal MN loss, respectively. This task is not only ecological, low-cost, efficient, and non-onerous, it also requires little animal handling and reduces the stress placed on the animal. It has long been a concern in the field that the SOD1 mouse does not display forelimb motor deficits and does not give researchers a complete picture of the disease. Here, we provide evidence that the SOD1 model does in fact develop early forelimb motor deficits due to the task's ability to assess fine-motor function, reconciling this model with the various clinical presentation of ALS. Taken together, the string-pulling paradigm may provide novel insights into the pathogenesis of ALS, offer nuanced evaluation of prospective treatments, and has high translational potential to the clinic.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33902769,

title = {The Canadian Brain Research Strategy: A Focus on Early Career Researchers},

author = {Caroline Menard and Tabrez J Siddiqui and Derya Sargin and Ashley Lawson and Yves De Koninck and Judy Illes},

doi = {10.1017/cjn.2021.81},

issn = {0317-1671},

year  = {2022},

date = {2022-03-01},

journal = {Can J Neurol Sci},

volume = {49},

number = {2},

pages = {168--170},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35058371,

title = {A Female-Specific Role for Calcitonin Gene-Related Peptide (CGRP) in Rodent Pain Models},

author = {Candler Paige and Isabel Plasencia-Fernandez and Moeno Kume and Melina Papalampropoulou-Tsiridou and Louis-Etienne Lorenzo and Eric T David and Lucy He and Galo L Mejia and Christopher Driskill and Francesco Ferrini and Andrew L Feldhaus and Leon F Garcia-Martinez and Armen N Akopian and Yves De Koninck and Gregory Dussor and Theodore J Price},

doi = {10.1523/JNEUROSCI.1137-21.2022},

issn = {1529-2401},

year  = {2022},

date = {2022-03-01},

journal = {J Neurosci},

volume = {42},

number = {10},

pages = {1930--1944},

abstract = {We aimed to investigate a sexually dimorphic role of calcitonin gene-related peptide (CGRP) in rodent models of pain. Based on findings in migraine where CGRP has a preferential pain-promoting effect in female rodents, we hypothesized that CGRP antagonists and antibodies would attenuate pain sensitization more efficaciously in female than male mice and rats. In hyperalgesic priming induced by activation of interleukin 6 signaling, CGRP receptor antagonists olcegepant and CGRP both given intrathecally, blocked, and reversed hyperalgesic priming only in females. A monoclonal antibody against CGRP, given systemically, blocked priming specifically in female rodents but failed to reverse it. In the spared nerve injury model, there was a transient effect of both CGRP antagonists, given intrathecally, on mechanical hypersensitivity in female mice only. Consistent with these findings, intrathecally applied CGRP caused a long-lasting, dose-dependent mechanical hypersensitivity in female mice but more transient effects in males. This CGRP-induced mechanical hypersensitivity was reversed by olcegepant and the KCC2 enhancer CLP257, suggesting a role for anionic plasticity in the dorsal horn in the pain-promoting effects of CGRP in females. In spinal dorsal horn slices, CGRP shifted GABA reversal potentials to significantly more positive values, but, again, only in female mice. Therefore, CGRP may regulate KCC2 expression and/or activity downstream of CGRP receptors specifically in females. However, KCC2 hypofunction promotes mechanical pain hypersensitivity in both sexes because CLP257 alleviated hyperalgesic priming in male and female mice. We conclude that CGRP promotes pain plasticity in female rodents but has a limited impact in males. The majority of patients impacted by chronic pain are women. Mechanistic studies in rodents are creating a clear picture that molecular events promoting chronic pain are different in male and female animals. We sought to build on evidence showing that CGRP is a more potent and efficacious promoter of headache in female than in male rodents. To test this, we used hyperalgesic priming and the spared nerve injury neuropathic pain models in mice. Our findings show a clear sex dimorphism wherein CGRP promotes pain in female but not male mice, likely via a centrally mediated mechanism of action. Our work suggests that CGRP receptor antagonists could be tested for efficacy in women for a broader variety of pain conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35379610,

title = {For a structured response to the psychosocial consequences of the restrictive measures imposed by the global COVID-19 health pandemic: the MAVIPAN longitudinal prospective cohort study protocol},

author = {Annie LeBlanc and Marie Baron and Patrick Blouin and George Tarabulsy and Francois Routhier and Catherine Mercier and Jean-Pierre Despres and Marc Hébert and Yves De Koninck and Caroline Cellard and Delphine Collin-Vézina and Nancy Côté and Émilie Dionne and Richard Fleet and Marie-Hélène Gagné and Maripier Isabelle and Lily Lessard and Matthew Menear and Chantal Merette and Marie-Christine Ouellet and Marc-André Roy and Marie-Christine Saint-Jacques and Claudia Savard and },

doi = {10.1136/bmjopen-2021-048749},

issn = {2044-6055},

year  = {2022},

date = {2022-04-01},

journal = {BMJ Open},

volume = {12},

number = {4},

pages = {e048749},

abstract = {INTRODUCTION: The COVID-19 pandemic and associated restrictive measures have caused important disruptions in economies and labour markets, changed the way we work and socialise, forced schools to close and healthcare and social services to reorganise. This unprecedented crisis forces individuals to make considerable efforts to adapt and will have psychological and social consequences, mainly on vulnerable individuals, that will remain once the pandemic is contained and will most likely exacerbate existing social and gender health inequalities. This crisis also puts a toll on the capacity of our healthcare and social services structures to provide timely and adequate care. The MAVIPAN (Ma vie et la pandémie/ My Life and the Pandemic) study aims to document how individuals, families, healthcare workers and health organisations are affected by the pandemic and how they adapt.nnMETHODS AND ANALYSIS: MAVIPAN is a 5-year longitudinal prospective cohort study launched in April 2020 across the province of Quebec (Canada). Quantitative data will be collected through online questionnaires (4-6 times/year) according to the evolution of the pandemic. Qualitative data will be collected with individual and group interviews and will seek to deepen our understanding of coping strategies. Analysis will be conducted under a mixed-method umbrella, with both sequential and simultaneous analyses of quantitative and qualitative data.nnETHICS AND DISSEMINATION: MAVIPAN aims to support the healthcare and social services system response by providing high-quality, real-time information needed to identify those who are most affected by the pandemic and by guiding public health authorities' decision making regarding intervention and resource allocation to mitigate these impacts. MAVIPAN was approved by the Ethics Committees of the Primary Care and Population Health Research Sector of CIUSSS de la Capitale-Nationale (Committee of record) and of the additional participating institutions.nnTRIAL REGISTRATION NUMBER: NCT04575571.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36337346,

title = {Distribution of acid-sensing ion channel subunits in human sensory neurons contrasts with that in rodents},

author = {Melina Papalampropoulou-Tsiridou and Stephanie Shiers and Feng Wang and Antoine G Godin and Theodore J Price and Yves De Koninck},

doi = {10.1093/braincomms/fcac256},

issn = {2632-1297},

year  = {2022},

date = {2022-01-01},

journal = {Brain Commun},

volume = {4},

number = {6},

pages = {fcac256},

abstract = {Acid-sensing ion channels (ASICs) play a critical role in nociception in human sensory neurons. Four genes ( and ) encoding multiple subunits through alternative splicing have been identified in humans. Real time-PCR experiments showed strong expression of three subunits , , and  in human dorsal root ganglia; however, their detailed expression pattern in different neuronal populations has not been investigated yet. In the current study, using an  hybridization approach (RNAscope), we examined the presence of , , and  mRNA in three subpopulations of human dorsal root ganglia neurons. Our results revealed that  and  were present in the vast majority of dorsal root ganglia neurons, while  was only expressed in less than half of dorsal root ganglia neurons. The distribution pattern of the three  subunits was the same across the three populations of dorsal root ganglia neurons examined, including neurons expressing the REarranged during Transfection (RET) receptor tyrosine kinase, calcitonin gene-related peptide, and a subpopulation of nociceptors expressing Transient Receptor Potential Cation Channel Subfamily V Member 1. These results strongly contrast the expression pattern of  in mice since our previous study demonstrated differential distribution of  among the various subpopulation of dorsal root ganglia neurons. Given the distinct acid-sensitivity and activity dynamics among different ASIC channels, the expression differences between human and rodents should be taken under consideration when evaluating the translational potential and efficiency of drugs targeting ASICs in rodent studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35579957,

title = {mTORC2 mediates structural plasticity in distal nociceptive endings that contributes to pain hypersensitivity following inflammation},

author = {Calvin Wong and Omer Barkai and Feng Wang and Carolina Thörn Perez and Shaya Lev and Weihua Cai and Shannon Tansley and Noosha Yousefpour and Mehdi Hooshmandi and Kevin C Lister and Mariam Latif and A Claudio Cuello and Masha Prager-Khoutorsky and Jeffrey S Mogil and Philippe Séguéla and Yves De Koninck and Alfredo Ribeiro-da-Silva and Alexander M Binshtok and Arkady Khoutorsky},

doi = {10.1172/JCI152635},

issn = {1558-8238},

year  = {2022},

date = {2022-08-01},

journal = {J Clin Invest},

volume = {132},

number = {15},

abstract = {The encoding of noxious stimuli into action potential firing is largely mediated by nociceptive free nerve endings. Tissue inflammation, by changing the intrinsic properties of the nociceptive endings, leads to nociceptive hyperexcitability and thus to the development of inflammatory pain. Here, we showed that tissue inflammation-induced activation of the mammalian target of rapamycin complex 2 (mTORC2) triggers changes in the architecture of nociceptive terminals and leads to inflammatory pain. Pharmacological activation of mTORC2 induced elongation and branching of nociceptor peripheral endings and caused long-lasting pain hypersensitivity. Conversely, nociceptor-specific deletion of the mTORC2 regulatory protein rapamycin-insensitive companion of mTOR (Rictor) prevented inflammation-induced elongation and branching of cutaneous nociceptive fibers and attenuated inflammatory pain hypersensitivity. Computational modeling demonstrated that mTORC2-mediated structural changes in the nociceptive terminal tree are sufficient to increase the excitability of nociceptors. Targeting mTORC2 using a single injection of antisense oligonucleotide against Rictor provided long-lasting alleviation of inflammatory pain hypersensitivity. Collectively, we showed that tissue inflammation-induced activation of mTORC2 causes structural plasticity of nociceptive free nerve endings in the epidermis and inflammatory hyperalgesia, representing a therapeutic target for inflammatory pain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35895817,

title = {Switch of serotonergic descending inhibition into facilitation by a spinal chloride imbalance in neuropathic pain},

author = {Franck Aby and Louis-Etienne Lorenzo and Zoé Grivet and Rabia Bouali-Benazzouz and Hugo Martin and Stéphane Valerio and Sara Whitestone and Dominique Isabel and Walid Idi and Otmane Bouchatta and Philippe De Deurwaerdere and Antoine G Godin and Cyril Herry and Xavier Fioramonti and Marc Landry and Yves De Koninck and Pascal Fossat},

doi = {10.1126/sciadv.abo0689},

issn = {2375-2548},

year  = {2022},

date = {2022-07-01},

journal = {Sci Adv},

volume = {8},

number = {30},

pages = {eabo0689},

abstract = {Descending control from the brain to the spinal cord shapes our pain experience, ranging from powerful analgesia to extreme sensitivity. Increasing evidence from both preclinical and clinical studies points to an imbalance toward descending facilitation as a substrate of pathological pain, but the underlying mechanisms remain unknown. We used an optogenetic approach to manipulate serotonin (5-HT) neurons of the nucleus raphe magnus that project to the dorsal horn of the spinal cord. We found that 5-HT neurons exert an analgesic action in naïve mice that becomes proalgesic in an experimental model of neuropathic pain. We show that spinal KCC2 hypofunction turns this descending inhibitory control into paradoxical facilitation; KCC2 enhancers restored 5-HT-mediated descending inhibition and analgesia. Last, combining selective serotonin reuptake inhibitors (SSRIs) with a KCC2 enhancer yields effective analgesia against nerve injury-induced pain hypersensitivity. This uncovers a previously unidentified therapeutic path for SSRIs against neuropathic pain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35323848,

title = {Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain},

author = {Annemarie Dedek and Jian Xu and Louis-Étienne Lorenzo and Antoine G Godin and Chaya M Kandegedara and Geneviève Glavina and Jeffrey A Landrigan and Paul J Lombroso and Yves De Koninck and Eve C Tsai and Michael E Hildebrand},

doi = {10.1093/brain/awab408},

issn = {1460-2156},

year  = {2022},

date = {2022-04-01},

journal = {Brain},

volume = {145},

number = {3},

pages = {1124--1138},

abstract = {The prevalence and severity of many chronic pain syndromes differ across sex, and recent studies have identified differences in immune signalling within spinal nociceptive circuits as a potential mediator. Although it has been proposed that sex-specific pain mechanisms converge once they reach neurons within the superficial dorsal horn, direct investigations using rodent and human preclinical pain models have been lacking. Here, we discovered that in the Freund's adjuvant in vivo model of inflammatory pain, where both male and female rats display tactile allodynia, a pathological coupling between KCC2-dependent disinhibition and N-methyl-D-aspartate receptor (NMDAR) potentiation within superficial dorsal horn neurons was observed in male but not female rats. Unlike males, the neuroimmune mediator brain-derived neurotrophic factor (BDNF) failed to downregulate inhibitory signalling elements (KCC2 and STEP61) and upregulate excitatory elements (pFyn, GluN2B and pGluN2B) in female rats, resulting in no effect of ex vivo brain-derived neurotrophic factor on synaptic NMDAR responses in female lamina I neurons. Importantly, this sex difference in spinal pain processing was conserved from rodents to humans. As in rodents, ex vivo spinal treatment with BDNF downregulated markers of disinhibition and upregulated markers of facilitated excitation in superficial dorsal horn neurons from male but not female human organ donors. Ovariectomy in female rats recapitulated the male pathological pain neuronal phenotype, with BDNF driving a coupling between disinhibition and NMDAR potentiation in adult lamina I neurons following the prepubescent elimination of sex hormones in females. This discovery of sexual dimorphism in a central neuronal mechanism of chronic pain across species provides a foundational step towards a better understanding and treatment for pain in both sexes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35617374,

title = {Microglia-mediated degradation of perineuronal nets promotes pain},

author = {Shannon Tansley and Ning Gu and Alba Ureña Guzmán and Weihua Cai and Calvin Wong and Kevin C Lister and Einer Muñoz-Pino and Noosha Yousefpour and R Brian Roome and Jordyn Heal and Neil Wu and Annie Castonguay and Graham Lean and Elizabeth M Muir and Artur Kania and Masha Prager-Khoutorsky and Ji Zhang and Christos G Gkogkas and James W Fawcett and Luda Diatchenko and Alfredo Ribeiro-da-Silva and Yves De Koninck and Jeffrey S Mogil and Arkady Khoutorsky},

doi = {10.1126/science.abl6773},

issn = {1095-9203},

year  = {2022},

date = {2022-07-01},

journal = {Science},

volume = {377},

number = {6601},

pages = {80--86},

abstract = {Activation of microglia in the spinal cord dorsal horn after peripheral nerve injury contributes to the development of pain hypersensitivity. How activated microglia selectively enhance the activity of spinal nociceptive circuits is not well understood. We discovered that after peripheral nerve injury, microglia degrade extracellular matrix structures, perineuronal nets (PNNs), in lamina I of the spinal cord dorsal horn. Lamina I PNNs selectively enwrap spinoparabrachial projection neurons, which integrate nociceptive information in the spinal cord and convey it to supraspinal brain regions to induce pain sensation. Degradation of PNNs by microglia enhances the activity of projection neurons and induces pain-related behaviors. Thus, nerve injury-induced degradation of PNNs is a mechanism by which microglia selectively augment the output of spinal nociceptive circuits and cause pain hypersensitivity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34800415,

title = {The International Brain Initiative: enabling collaborative science},

author = {Gianluca Quaglio and Patrizia Toia and Edvard I Moser and Theodoros Karapiperis and Katrin Amunts and Shigeo Okabe and Mu-Ming Poo and Jong-Cheol Rah and Yves De Koninck and John Ngai and Linda Richards and Jan G Bjaalie},

doi = {10.1016/S1474-4422(21)00389-6},

issn = {1474-4465},

year  = {2021},

date = {2021-12-01},

journal = {Lancet Neurol},

volume = {20},

number = {12},

pages = {985--986},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34504415,

title = {A Wireless Electro-Optic Platform for Multimodal Electrophysiology and Optogenetics in Freely Moving Rodents},

author = {Guillaume Bilodeau and Gabriel Gagnon-Turcotte and Léonard L Gagnon and Iason Keramidis and Igor Timofeev and Yves De Koninck and Christian Ethier and Benoit Gosselin},

doi = {10.3389/fnins.2021.718478},

issn = {1662-4548},

year  = {2021},

date = {2021-01-01},

journal = {Front Neurosci},

volume = {15},

pages = {718478},

abstract = {This paper presents the design and the utilization of a wireless electro-optic platform to perform simultaneous multimodal electrophysiological recordings and optogenetic stimulation in freely moving rodents. The developed system can capture neural action potentials (AP), local field potentials (LFP) and electromyography (EMG) signals with up to 32 channels in parallel while providing four optical stimulation channels. The platform is using commercial off-the-shelf components (COTS) and a low-power digital field-programmable gate array (FPGA), to perform digital signal processing to digitally separate in real time the AP, LFP and EMG while performing signal detection and compression for mitigating wireless bandwidth and power consumption limitations. The different signal modalities collected on the 32 channels are time-multiplexed into a single data stream to decrease power consumption and optimize resource utilization. The data reduction strategy is based on signal processing and real-time data compression. Digital filtering, signal detection, and wavelet data compression are used inside the platform to separate the different electrophysiological signal modalities, namely the local field potentials (1-500 Hz), EMG (30-500 Hz), and the action potentials (300-5,000 Hz) and perform data reduction before transmitting the data. The platform achieves a measured data reduction ratio of 7.77 (for a firing rate of 50 AP/second) and weights 4.7 g with a 100-mAh battery, an on/off switch and a protective plastic enclosure. To validate the performance of the platform, we measured distinct electrophysiology signals and performed optogenetics stimulation  in freely moving rondents. We recorded AP and LFP signals with the platform using a 16-microelectrode array implanted in the primary motor cortex of a Long Evans rat, both in anesthetized and freely moving conditions. EMG responses to optogenetic Channelrhodopsin-2 induced activation of motor cortex  optical fiber were also recorded in freely moving rodents.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32769979,

title = {Differential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization},

author = {Francesco Ferrini and Jimena Perez-Sanchez and Samuel Ferland and Louis-Etienne Lorenzo and Antoine G Godin and Isabel Plasencia-Fernandez and Martin Cottet and Annie Castonguay and Feng Wang and Chiara Salio and Nicolas Doyon and Adalberto Merighi and Yves De Koninck},

doi = {10.1038/s41467-020-17824-y},

issn = {2041-1723},

year  = {2020},

date = {2020-08-01},

journal = {Nat Commun},

volume = {11},

number = {1},

pages = {3935},

abstract = {GABA/glycine-mediated neuronal inhibition critically depends on intracellular chloride (Cl) concentration which is mainly regulated by the K-Cl co-transporter 2 (KCC2) in the adult central nervous system (CNS). KCC2 heterogeneity thus affects information processing across CNS areas. Here, we uncover a gradient in Cl extrusion capacity across the superficial dorsal horn (SDH) of the spinal cord (laminae I-II: LI-LII), which remains concealed under low Cl load. Under high Cl load or heightened synaptic drive, lower Cl extrusion is unveiled in LI, as expected from the gradient in KCC2 expression found across the SDH. Blocking TrkB receptors increases KCC2 in LI, pointing to differential constitutive TrkB activation across laminae. Higher Cl lability in LI results in rapidly collapsing inhibition, and a form of activity-dependent synaptic plasticity expressed as a continuous facilitation of excitatory responses. The higher metaplasticity in LI as compared to LII differentially affects sensitization to thermal and mechanical input. Thus, inconspicuous heterogeneity of Cl extrusion across laminae critically shapes plasticity for selective nociceptive modalities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33083721,

title = {Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia},

author = {Weilai Dong and Sheng Chih Jin and August Allocco and Xue Zeng and Amar H Sheth and Shreyas Panchagnula and Annie Castonguay and Louis-Étienne Lorenzo and Barira Islam and Geneviève Brindle and Karine Bachand and Jamie Hu and Agata Sularz and Jonathan Gaillard and Jungmin Choi and Ashley Dunbar and Carol Nelson-Williams and Emre Kiziltug and Charuta Gavankar Furey and Sierra Conine and Phan Q Duy and Adam J Kundishora and Erin Loring and Boyang Li and Qiongshi Lu and Geyu Zhou and Wei Liu and Xinyue Li and Michael C Sierant and Shrikant Mane and Christopher Castaldi and Francesc López-Giráldez and James R Knight and Raymond F Sekula and J Marc Simard and Emad N Eskandar and Christopher Gottschalk and Jennifer Moliterno and Murat Günel and Jason L Gerrard and Sulayman Dib-Hajj and Stephen G Waxman and Fred G Barker and Seth L Alper and Mohamed Chahine and Shozeb Haider and Yves De Koninck and Richard P Lifton and Kristopher T Kahle},

doi = {10.1016/j.isci.2020.101552},

issn = {2589-0042},

year  = {2020},

date = {2020-10-01},

journal = {iScience},

volume = {23},

number = {10},

pages = {101552},

abstract = {Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated  mutation (p.Cys188Trp) in the GABA receptor Cl channel γ-1 subunit () exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na and Ca channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca channel Ca3.2 (). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31972144,

title = {International Brain Initiative: An Innovative Framework for Coordinated Global Brain Research Efforts},

author = { and },

doi = {10.1016/j.neuron.2020.01.002},

issn = {1097-4199},

year  = {2020},

date = {2020-01-01},

journal = {Neuron},

volume = {105},

number = {2},

pages = {212--216},

abstract = {The International Brain Initiative (IBI) has been established to coordinate efforts across existing and emerging national and regional brain initiatives. This NeuroView describes how to be involved and the new opportunities for global collaboration that are emerging between scientists, scientific societies, funders, industry, government, and society.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32054836,

title = {Enhancing neuronal chloride extrusion rescues α2/α3 GABA-mediated analgesia in neuropathic pain},

author = {Louis-Etienne Lorenzo and Antoine G Godin and Francesco Ferrini and Karine Bachand and Isabel Plasencia-Fernandez and Simon Labrecque and Alexandre A Girard and Dominic Boudreau and Irenej Kianicka and Martin Gagnon and Nicolas Doyon and Alfredo Ribeiro-da-Silva and Yves De Koninck},

doi = {10.1038/s41467-019-14154-6},

issn = {2041-1723},

year  = {2020},

date = {2020-02-01},

journal = {Nat Commun},

volume = {11},

number = {1},

pages = {869},

abstract = {Spinal disinhibition has been hypothesized to underlie pain hypersensitivity in neuropathic pain. Apparently contradictory mechanisms have been reported, raising questions on the best target to produce analgesia. Here, we show that nerve injury is associated with a reduction in the number of inhibitory synapses in the spinal dorsal horn. Paradoxically, this is accompanied by a BDNF-TrkB-mediated upregulation of synaptic GABARs and by an α1-to-α2GABAR subunit switch, providing a mechanistic rationale for the analgesic action of the α2,3GABAR benzodiazepine-site ligand L838,417 after nerve injury. Yet, we demonstrate that impaired Cl extrusion underlies the failure of L838,417 to induce analgesia at high doses due to a resulting collapse in Cl gradient, dramatically limiting the benzodiazepine therapeutic window. In turn, enhancing KCC2 activity not only potentiated L838,417-induced analgesia, it rescued its analgesic potential at high doses, revealing a novel strategy for analgesia in pathological pain, by combined targeting of the appropriate GABAR-subtypes and restoring Cl homeostasis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32203578,

title = {Cortical interneuron-mediated inhibition delays the onset of amyotrophic lateral sclerosis},

author = {C Sahara Khademullah and Afif J Aqrabawi and Kara M Place and Zahra Dargaei and Xinyi Liang and Jessica C Pressey and Simon Bedard and Jy Wei Yang and Danielle Garand and Iason Keramidis and Alicja Gasecka and Daniel Côté and Yves De Koninck and Julia Keith and Lorne Zinman and Janice Robertson and Jun Chul Kim and Melanie A Woodin},

doi = {10.1093/brain/awaa034},

issn = {1460-2156},

year  = {2020},

date = {2020-03-01},

journal = {Brain},

volume = {143},

number = {3},

pages = {800--810},

abstract = {Amyotrophic lateral sclerosis is a fatal disease resulting from motor neuron degeneration in the cortex and spinal cord. Cortical hyperexcitability is a hallmark feature of amyotrophic lateral sclerosis and is accompanied by decreased intracortical inhibition. Using electrophysiological patch-clamp recordings, we revealed parvalbumin interneurons to be hypoactive in the late pre-symptomatic SOD1*G93A mouse model of amyotrophic lateral sclerosis. We discovered that using adeno-associated virus-mediated delivery of chemogenetic technology targeted to increase the activity of the interneurons within layer 5 of the primary motor cortex, we were able to rescue intracortical inhibition and reduce pyramidal neuron hyperexcitability. Increasing the activity of interneurons in the layer 5 of the primary motor cortex was effective in delaying the onset of amyotrophic lateral sclerosis-associated motor deficits, slowing symptom progression, preserving neuronal populations, and increasing the lifespan of SOD1*G93A mice. Taken together, this study provides novel insights into the pathogenesis and treatment of amyotrophic lateral sclerosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32206678,

title = {Anisotropic light scattering from myelinated axons in the spinal cord},

author = {Damon DePaoli and Alicja Gasecka and Mohamed Bahdine and Jean M Deschenes and Laurent Goetz and Jimena Perez-Sanchez and Robert P Bonin and Yves De Koninck and Martin Parent and Daniel C Côté},

doi = {10.1117/1.NPh.7.1.015011},

issn = {2329-423X},

year  = {2020},

date = {2020-01-01},

journal = {Neurophotonics},

volume = {7},

number = {1},

pages = {015011},

abstract = {Optogenetics has become an integral tool for studying and dissecting the neural circuitries of the brain using optical control. Recently, it has also begun to be used in the investigation of the spinal cord and peripheral nervous system. However, information on these regions' optical properties is sparse. Moreover, there is a lack of data on the dependence of light propagation with respect to neural tissue organization and orientation. This information is important for effective simulations and optogenetic planning, particularly in the spinal cord where the myelinated axons are highly organized. To this end, we report experimental measurements for the scattering coefficient, validated with three different methods in both the longitudinal and radial directions of multiple mammalian spinal cords. In our analysis, we find that there is indeed a directional dependence of photon propagation when interacting with organized myelinated axons. Specifically, light propagating perpendicular to myelinated axons in the white matter of the spinal cord produced a measured reduced scattering coefficient (  ) of  , and light that was propagated along the myelinated axons in the white matter produced a measured  of  , across the various species considered. This 50% decrease in scattering power along the myelinated axons is observed with three different measurement strategies (integrating spheres, observed transmittance, and punch-through method). Furthermore, this directional dependence in scattering power and overall light attenuation did not occur in the gray matter regions where the myelin organization is nearly random. The acquired information will be integral in preparing future light-transport simulations and in overall optogenetic planning in both the spinal cord and the brain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32573694,

title = {Neuronal interleukin-1 receptors mediate pain in chronic inflammatory diseases},

author = {Benoit Mailhot and Marine Christin and Nicolas Tessandier and Chaudy Sotoudeh and Floriane Bretheau and Roxanne Turmel and Ève Pellerin and Feng Wang and Cyril Bories and Charles Joly-Beauparlant and Yves De Koninck and Arnaud Droit and Francesca Cicchetti and Grégory Scherrer and Eric Boilard and Reza Sharif-Naeini and Steve Lacroix},

doi = {10.1084/jem.20191430},

issn = {1540-9538},

year  = {2020},

date = {2020-09-01},

journal = {J Exp Med},

volume = {217},

number = {9},

abstract = {Chronic pain is a major comorbidity of chronic inflammatory diseases. Here, we report that the cytokine IL-1β, which is abundantly produced during multiple sclerosis (MS), arthritis (RA), and osteoarthritis (OA) both in humans and in animal models, drives pain associated with these diseases. We found that the type 1 IL-1 receptor (IL-1R1) is highly expressed in the mouse and human by a subpopulation of TRPV1+ dorsal root ganglion neurons specialized in detecting painful stimuli, termed nociceptors. Strikingly, deletion of the Il1r1 gene specifically in TRPV1+ nociceptors prevented the development of mechanical allodynia without affecting clinical signs and disease progression in mice with experimental autoimmune encephalomyelitis and K/BxN serum transfer-induced RA. Conditional restoration of IL-1R1 expression in nociceptors of IL-1R1-knockout mice induced pain behavior but did not affect joint damage in monosodium iodoacetate-induced OA. Collectively, these data reveal that neuronal IL-1R1 signaling mediates pain, uncovering the potential benefit of anti-IL-1 therapies for pain management in patients with chronic inflammatory diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32508593,

title = {Differential Expression of Acid - Sensing Ion Channels in Mouse Primary Afferents in Naïve and Injured Conditions},

author = {Melina Papalampropoulou-Tsiridou and Simon Labrecque and Antoine G Godin and Yves De Koninck and Feng Wang},

doi = {10.3389/fncel.2020.00103},

issn = {1662-5102},

year  = {2020},

date = {2020-01-01},

journal = {Front Cell Neurosci},

volume = {14},

pages = {103},

abstract = {Injury and inflammation cause tissue acidosis, which is a common feature of various painful conditions. Acid-Sensing Ion channels (ASICs) are amongst the main excitatory channels activated by extracellular protons and expressed in the nervous system. Six transcripts of ASIC subunits including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, and ASIC4 are encoded by four genes (Asic1-4) and have been identified in rodents. Most ASIC subunits are present at substantial levels in primary sensory neurons of dorsal root ganglia (DRG) except for ASIC4. However, their expression pattern in DRG neurons remains largely unclear, mainly due to the lack of antibodies with appropriate specificity. In this study, we examined in detail the expression pattern of ASIC1-3 subunits, including splice variants, in different populations of DRG neurons in adult mice using an  hybridization technique (RNAscope) with high sensitivity and specificity. We found that in naïve condition, all five subunits examined were expressed in the majority of myelinated, NF200-immunoreactive, DRG neurons (NF200). However, ASIC subunits showed a very different expression pattern among non-myelinated DRG neuronal subpopulations: ASIC1 and ASIC3 were only expressed in CGRP-immunoreactive neurons (CGRP), ASIC2a was mostly expressed in the majority of IB4-binding neurons (IB4), while ASIC2b was expressed in almost all non-myelinated DRG neurons. We also found that at least half of sensory neurons expressed multiple types of ASIC subunits, indicating prevalence of heteromeric channels. In mice with peripheral nerve injury, the expression level of ASIC1a and ASIC1b in L4 DRG and ASIC3 in L5 DRG were altered in CGRP neurons, but not in IB4 neurons. Furthermore, the pattern of change varied among DRGs depending on their segmental level, which pointed to differential regulatory mechanisms between afferent types and anatomical location. The distinct expression pattern of ASIC transcripts in naïve condition, and the differential regulation of ASIC subunits after peripheral nerve injury, suggest that ASIC subunits are involved in separate sensory modalities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32243847,

title = {Developmental Potential and Plasticity of Olfactory Epithelium Stem Cells Revealed by Heterotopic Grafting in the Adult Brain},

author = {Qian Li and Tiziano Siri and Cedric Bressan and Yves de Koninck and Armen Saghatelyan},

doi = {10.1016/j.stemcr.2020.03.008},

issn = {2213-6711},

year  = {2020},

date = {2020-04-01},

journal = {Stem Cell Reports},

volume = {14},

number = {4},

pages = {692--702},

abstract = {The neural stem cells (NSCs) residing in the olfactory epithelium (OE) regenerate damaged olfactory sensory neurons throughout adulthood. The accessibility and availability of these NSCs in living individuals, including humans, makes them a promising candidate for harvesting their potential for cell replacement therapies. However, this requires an in-depth understanding of their developmental potential after grafting. Here, we investigated the developmental potential and plasticity of mouse OE-derived NSCs after grafting into the adult subventricular zone (SVZ) neurogenic niche. Our results showed that OE-derived NSCs integrate and proliferate just like endogenous SVZ stem cells, migrate with similar dynamics as endogenous neuroblasts toward the olfactory bulb, and mature and acquire similar electrophysiological properties as endogenous adult-born bulbar interneurons. These results reveal the developmental potential and plasticity of OE-derived NSCs in vivo and show that they can respond to heterotopic neurogenic cues to adapt their phenotype and become functional neurons in ectopic brain regions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31315039,

title = {Chloride Dysregulation through Downregulation of KCC2 Mediates Neuropathic Pain in Both Sexes},

author = {Josiane C S Mapplebeck and Louis-Etienne Lorenzo and Kwan Yeop Lee and Cédric Gauthier and Milind M Muley and Yves De Koninck and Steven A Prescott and Michael W Salter},

doi = {10.1016/j.celrep.2019.06.059},

issn = {2211-1247},

year  = {2019},

date = {2019-07-01},

journal = {Cell Rep},

volume = {28},

number = {3},

pages = {590--596.e4},

abstract = {The behavioral features of neuropathic pain are not sexually dimorphic despite sex differences in the underlying neuroimmune signaling. This raises questions about whether neural processing is comparably altered. Here, we test whether the K-Cl co-transporter KCC2, which regulates synaptic inhibition, plays an equally important role in development of neuropathic pain in male and female rodents. Past studies on KCC2 tested only males. We find that inhibiting KCC2 in uninjured animals reproduces behavioral and electrophysiological features of neuropathic pain in both sexes and, consistent with equivalent injury-induced downregulation of KCC2, that counteracting chloride dysregulation reverses injury-induced behavioral and electrophysiological changes in both sexes. These findings demonstrate that KCC2 downregulation contributes equally to pain hypersensitivity in males and females. Whereas diverse (and sexually dimorphic) mechanisms regulate KCC2, regulation of intracellular chloride relies almost exclusively on KCC2. Directly targeting KCC2 thus remains a promising strategy for treatment of neuropathic pain in both sexes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29968500,

title = {Amiloride modulation of carbon dioxide hypersensitivity and thermal nociceptive hypersensitivity induced by interference with early maternal environment},

author = {Marco Battaglia and Orlane Rossignol and Karine Bachand and Francesca R D'Amato and Yves De Koninck},

doi = {10.1177/0269881118784872},

issn = {1461-7285},

year  = {2019},

date = {2019-01-01},

journal = {J Psychopharmacol},

volume = {33},

number = {1},

pages = {101--108},

abstract = {BACKGROUND: Early life adversities are risk factors for anxiety disorders and for pain syndromes, which are, in turn, highly comorbid with anxiety disorders. Repeated cross-fostering mouse pups to adoptive lactating females induces epigenetic modification and heightened mRNA-expression of the acid-sensing-ion-channel-1 gene, altered nociception, and hypersensitivity to 6% carbon dioxide air mixtures, a trait marker of specific human anxiety disorders such as, most clearly and prominently, panic disorder.nnAIMS: We hypothesized that the acid-sensing ion channel inhibitor amiloride can modulate repeated cross-fostering animals' exaggerated responses to carbon dioxide and nociceptive thermal stimulation.nnMETHODS: Respiratory carbon dioxide sensitivity was assessed by plethysmography during 6% carbon dioxide air mixture challenges, and nociception was assessed by latency of paw withdrawal to thermal stimulation, in repeated cross-fostering and control animals. To circumvent the blood-brain barrier, prior to testing, amiloride was nebulized in a plethysmograph. Data were analyzed by general linear models.nnRESULTS: Analyses of tidal volume responses to 6% carbon dioxide of animals pre-treated with nebulized amiloride/saline in a randomized crossover design showed significant modulatory effect of amiloride, and amiloride×repeated cross-fostering interaction. In contrast, repeated cross-fostering animals' responses to 6% carbon dioxide after intraperitoneal amiloride, saline, or no treatment, were no different. Analyses of responses to thermal stimuli showed a significant modulatory effect of nebulized amiloride, and repeated cross-fostering×amiloride interaction.nnCONCLUSIONS: Single-dose nebulized amiloride decreased repeated cross-fostering animals' carbon dioxide sensitivity and nociception indices to levels that were no different from those of control animals. Inasmuch as these results pertain to human anxiety and/or pain hypersensitivity, our findings provide a rationale for studying inhaled amiloride in some anxiety disorders and/or pain syndromes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31135041,

title = {Loss of STEP61 couples disinhibition to N-methyl-d-aspartate receptor potentiation in rodent and human spinal pain processing},

author = {Annemarie Dedek and Jian Xu and Chaya M Kandegedara and Louis-Étienne Lorenzo and Antoine G Godin and Yves De Koninck and Paul J Lombroso and Eve C Tsai and Michael E Hildebrand},

doi = {10.1093/brain/awz105},

issn = {1460-2156},

year  = {2019},

date = {2019-06-01},

journal = {Brain},

volume = {142},

number = {6},

pages = {1535--1546},

abstract = {Dysregulated excitability within the spinal dorsal horn is a critical mediator of chronic pain. In the rodent nerve injury model of neuropathic pain, BDNF-mediated loss of inhibition (disinhibition) gates the potentiation of excitatory GluN2B N-methyl-d-aspartate receptor (NMDAR) responses at lamina I dorsal horn synapses. However, the centrality of this mechanism across pain states and species, as well as the molecular linker involved, remain unknown. Here, we show that KCC2-dependent disinhibition is coupled to increased GluN2B-mediated synaptic NMDAR responses in a rodent model of inflammatory pain, with an associated downregulation of the tyrosine phosphatase STEP61. The decreased activity of STEP61 is both necessary and sufficient to prime subsequent phosphorylation and potentiation of GluN2B NMDAR by BDNF at lamina I synapses. Blocking disinhibition reversed the downregulation of STEP61 as well as inflammation-mediated behavioural hypersensitivity. For the first time, we characterize GluN2B-mediated NMDAR responses at human lamina I synapses and show that a human ex vivo BDNF model of pathological pain processing downregulates KCC2 and STEP61 and upregulates phosphorylated GluN2B at dorsal horn synapses. Our results demonstrate that STEP61 is the molecular brake that is lost following KCC2-dependent disinhibition and that the decrease in STEP61 activity drives the potentiation of excitatory GluN2B NMDAR responses in rodent and human models of pathological pain. The ex vivo human BDNF model may thus form a translational bridge between rodents and humans for identification and validation of novel molecular pain targets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31352352,

title = {A Wireless Electro-Optic Headstage With a 0.13- μm CMOS Custom Integrated DWT Neural Signal Decoder for Closed-Loop Optogenetics},

author = {Gabriel Gagnon-Turcotte and Iason Keramidis and Christian Ethier and Yves De Koninck and Benoit Gosselin},

doi = {10.1109/TBCAS.2019.2930498},

issn = {1940-9990},

year  = {2019},

date = {2019-10-01},

journal = {IEEE Trans Biomed Circuits Syst},

volume = {13},

number = {5},

pages = {1036--1051},

abstract = {We present a wireless electro-optic headstage that uses a 0.13- μm CMOS custom integrated circuit (IC) implementing a digital neural decoder (ND-IC) for enabling real-time closed-loop (CL) optogenetics. The ND-IC processes the neural activity data using three digital cores: 1) the detector core detects and extracts the action potential (AP) of individual neurons by using an adaptive threshold; 2) the data compression core compresses the detected AP by using an efficient Symmlet-2 discrete wavelet transform (DWT) processor for decreasing the amount of data to be transmitted by the low-power wireless link; and 3) the classification core sorts the compressed AP into separated clusters on the fly according to their wave shapes. The ND-IC encompasses several innovations: 1) the compression core decreases the complexity from O(n ) to O(n · log(n)) compared to the previous solutions, while using two times less memory, thanks to the use of a new coefficient sorting tree; and 2) the AP classification core reuses both the compressed DWT coefficients to perform implicit dimensionality reduction, which allows for performing intensive signal processing on-chip, while increasing power and hardware efficiency. This core also reuses the signal standard deviation already computed by the AP detector core as threshold for performing automatic AP sorting. The headstage also introduces innovations by enabling a new wireless CL scheme between the neural data acquisition module and the optical stimulator. Our CL scheme uses the AP sorting and timing information produced by the ND-IC for detecting complex firing patterns within the brain. The headstage is also smaller (1.13 cm ), lighter (3.0 g with a 40 mAh battery) and less invasive than the previous solutions, while providing a measured autonomy of 2h40, with the ND-IC. The whole system and the ND-IC are first validated in vivo in the LD thalamus of a Long-Evans rat, and then in freely-moving CL experiments involving a mouse virally expressing ChR2-mCherry in inhibitory neurons of the prelimbic cortex, and the results show that our system works well within an in vivo experimental setting with a freely moving mouse.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31223654,

title = {Sortilin gates neurotensin and BDNF signaling to control peripheral neuropathic pain},

author = {Mette Richner and Lone T Pallesen and Maj Ulrichsen and Ebbe T Poulsen and Thomas H Holm and Hande Login and Annie Castonguay and Louis-Etienne Lorenzo and Nádia P Gonçalves and Olav M Andersen and Karin Lykke-Hartmann and Jan J Enghild and Lars C B Rønn and Ibrahim J Malik and Yves De Koninck and Ole J Bjerrum and Christian B Vægter and Anders Nykjær},

doi = {10.1126/sciadv.aav9946},

issn = {2375-2548},

year  = {2019},

date = {2019-06-01},

journal = {Sci Adv},

volume = {5},

number = {6},

pages = {eaav9946},

abstract = {Neuropathic pain is a major incurable clinical problem resulting from peripheral nerve trauma or disease. A central mechanism is the reduced expression of the potassium chloride cotransporter 2 (KCC2) in dorsal horn neurons induced by brain-derived neurotrophic factor (BDNF), causing neuronal disinhibition within spinal nociceptive pathways. Here, we demonstrate how neurotensin receptor 2 (NTSR2) signaling impairs BDNF-induced spinal KCC2 down-regulation, showing how these two pathways converge to control the abnormal sensory response following peripheral nerve injury. We establish how sortilin regulates this convergence by scavenging neurotensin from binding to NTSR2, thus modulating its inhibitory effect on BDNF-mediated mechanical allodynia. Using sortilin-deficient mice or receptor inhibition by antibodies or a small-molecule antagonist, we lastly demonstrate that we are able to fully block BDNF-induced pain and alleviate injury-induced neuropathic pain, validating sortilin as a clinically relevant target.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30731060,

title = {A Neuroethics Backbone for the Evolving Canadian Brain Research Strategy},

author = {Judy Illes and Samuel Weiss and Jaideep Bains and Jennifer A Chandler and Patricia Conrod and Yves De Koninck and Lesley K Fellows and Deanna Groetzinger and Eric Racine and Julie M Robillard and Marla B Sokolowski},

doi = {10.1016/j.neuron.2018.12.021},

issn = {1097-4199},

year  = {2019},

date = {2019-02-01},

journal = {Neuron},

volume = {101},

number = {3},

pages = {370--374},

abstract = {Building on Canada's strong traditions in neuroscience and ethics, neuroethics provides a backbone for the evolving Canadian Brain Research Strategy (CBRS) that, from the outset, incorporates ethically responsible discoveries in brain science into clinical, societal, educational, and commercial innovation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29877814,

title = {A Wireless Fiber Photometry System Based on a High-Precision CMOS Biosensor With Embedded Continuous-Time Modulation},

author = {Mehdi Noormohammadi Khiarak and Ekaterina Martianova and Cyril Bories and Sylvain Martel and Christophe D Proulx and Yves De Koninck and Benoit Gosselin},

doi = {10.1109/TBCAS.2018.2817200},

issn = {1940-9990},

year  = {2018},

date = {2018-06-01},

journal = {IEEE Trans Biomed Circuits Syst},

volume = {12},

number = {3},

pages = {495--509},

abstract = {Fluorescence biophotometry measurements require wide dynamic range (DR) and high-sensitivity laboratory apparatus. Indeed, it is often very challenging to accurately resolve the small fluorescence variations in presence of noise and high-background tissue autofluorescence. There is a great need for smaller detectors combining high linearity, high sensitivity, and high-energy efficiency. This paper presents a new biophotometry sensor merging two individual building blocks, namely a low-noise sensing front-end and a order continuous-time modulator (CTSDM), into a single module for enabling high-sensitivity and high energy-efficiency photo-sensing. In particular, a differential CMOS photodetector associated with a differential capacitive transimpedance amplifier-based sensing front-end is merged with an incremental order 1-bit CTSDM to achieve a large DR, low hardware complexity, and high-energy efficiency. The sensor leverages a hardware sharing strategy to simplify the implementation and reduce power consumption. The proposed CMOS biosensor is integrated within a miniature wireless head mountable prototype for enabling biophotometry with a single implantable fiber in the brain of live mice. The proposed biophotometry sensor is implemented in a 0.18- CMOS technology, consuming from a 1.8- supply voltage, while achieving a peak dynamic range of over a 50- input bandwidth, a sensitivity of 24 mV/nW, and a minimum detectable current of 2.46- at a 20- sampling rate.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30469598,

title = {Resolution enhancement in laser scanning microscopy with deconvolution switching laser modes (D-SLAM)},

author = {Louis Thibon and Michel Piché and Yves De Koninck},

doi = {10.1364/OE.26.024881},

issn = {1094-4087},

year  = {2018},

date = {2018-09-01},

journal = {Opt Express},

volume = {26},

number = {19},

pages = {24881--24903},

abstract = {Laser scanning microscopy is limited in lateral resolution by the diffraction of light. Superresolution methods have been developed since the 90s to overcome this limitation. However superresolution is generally achieved at the expense of a greater complexity (high power lasers, very long acquisition times, specific fluorophores) and limitations on the observable samples. In this paper we propose a method to improve the resolution of confocal microscopy by combining different laser modes and deconvolution. Two images of the same field are acquired with the confocal microscope using different laser modes and used as inputs to a deconvolution algorithm. The two laser modes have different Point Spread Functions and thus provide complementary information leading to an image with enhanced resolution compared to using a single confocal image as input to the same deconvolution algorithm. By changing the laser modes to Bessel-Gauss beams we were able to further improve the efficiency of the deconvolution algorithm and obtain images with a residual Point Spread Function having a width of 0.14 λ (72 nm at a wavelength of 532 nm). This method only requires a laser scanning microscope and is not dependent on certain specific properties of fluorescent proteins. The proposed method requires only a few add-ons to classical confocal or two-photon microscopes and can easily be retrofitted into an existing commercial laser scanning microscope.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29570055,

title = {A Low-Power Current-Reuse Analog Front-End for High-Density Neural Recording Implants},

author = {Masoud Rezaei and Esmaeel Maghsoudloo and Cyril Bories and Yves De Koninck and Benoit Gosselin},

doi = {10.1109/TBCAS.2018.2805278},

issn = {1940-9990},

year  = {2018},

date = {2018-04-01},

journal = {IEEE Trans Biomed Circuits Syst},

volume = {12},

number = {2},

pages = {271--280},

abstract = {Studying brain activity in vivo requires collecting bioelectrical signals from several microelectrodes simultaneously in order to capture neuron interactions. In this work, we present a new current-reuse analog front-end (AFE), which is scalable to very large numbers of recording channels, thanks to its small implementation silicon area and its low-power consumption. This current-reuse AFE, which is including a low-noise amplifier (LNA) and a programmable gain amplifier (PGA), employs a new fully differential current-mirror topology using fewer transistors, and improving several design parameters, such as power consumption and noise, over previous current-reuse amplifier circuit implementations. We show that the proposed current-reuse amplifier can provide a theoretical noise efficiency factor (NEF) as low as 1.01, which is the lowest reported theoretical NEF provided by an LNA topology. A foue-channel current-reuse AFE implemented in a CMOS 0.18-μm technology is presented as a proof-of-concept. T-network capacitive circuits are used to decrease the size of input capacitors and to increase the gain accuracy in the AFE. The measured performance of the whole AFE is presented. The total power consumption per channel, including the LNA and the PGA stage, is 9 μW (4.5 μW for LNA and 4.5 μW for PGA), for an input referred noise of 3.2 μV, achieving a measured NEF of 1.94. The entire AFE presents three selectable gains of 35.04, 43.1, and 49.5 dB, and occupies a die area of 0.072 mm per channel. The implemented circuit has a measured inter-channel rejection ratio of 54 dB. In vivo recording results obtained with the proposed AFE are reported. It successfully allows collecting low-amplitude extracellular action potential signals from a tungsten wire microelectrode implanted in the hippocampus of a laboratory mouse.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29768200,

title = {Sensory Afferents Use Different Coding Strategies for Heat and Cold},

author = {Feng Wang and Erik Bélanger and Sylvain L Côté and Patrick Desrosiers and Steven A Prescott and Daniel C Côté and Yves De Koninck},

doi = {10.1016/j.celrep.2018.04.065},

issn = {2211-1247},

year  = {2018},

date = {2018-05-01},

journal = {Cell Rep},

volume = {23},

number = {7},

pages = {2001--2013},

abstract = {Primary afferents transduce environmental stimuli into electrical activity that is transmitted centrally to be decoded into corresponding sensations. However, it remains unknown how afferent populations encode different somatosensory inputs. To address this, we performed two-photon Ca imaging from thousands of dorsal root ganglion (DRG) neurons in anesthetized mice while applying mechanical and thermal stimuli to hind paws. We found that approximately half of all neurons are polymodal and that heat and cold are encoded very differently. As temperature increases, more heating-sensitive neurons are activated, and most individual neurons respond more strongly, consistent with graded coding at population and single-neuron levels, respectively. In contrast, most cooling-sensitive neurons respond in an ungraded fashion, inconsistent with graded coding and suggesting combinatorial coding, based on which neurons are co-activated. Although individual neurons may respond to multiple stimuli, our results show that different stimuli activate distinct combinations of diversely tuned neurons, enabling rich population-level coding.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29765159,

title = {Transition to chronic pain: opportunities for novel therapeutics},

author = {Theodore J Price and Allan I Basbaum and Jacqueline Bresnahan and Jan F Chambers and Yves De Koninck and Robert R Edwards and Ru-Rong Ji and Joel Katz and Annemieke Kavelaars and Jon D Levine and Linda Porter and Neil Schechter and Kathleen A Sluka and Gregory W Terman and Tor D Wager and Tony L Yaksh and Robert H Dworkin},

doi = {10.1038/s41583-018-0012-5},

issn = {1471-0048},

year  = {2018},

date = {2018-07-01},

journal = {Nat Rev Neurosci},

volume = {19},

number = {7},

pages = {383--384},

abstract = {Although chronic pain is one of the most important medical problems facing society, there has been very limited progress in the development of novel therapies for this condition. Here, we discuss high-impact research priorities to reduce the number of people transitioning from acute to chronic intractable pain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29216044,

title = {Reply to The small molecule CLP257 does not modify activity of the K-Cl co-transporter KCC2 but does potentiate GABA receptor activity},

author = {Martin Gagnon and Marc J Bergeron and Jimena Perez-Sanchez and Isabel Plasencia-Fernández and Louis-Etienne Lorenzo and Antoine G Godin and Annie Castonguay and Robert P Bonin and Yves De Koninck},

doi = {10.1038/nm.4449},

issn = {1546-170X},

year  = {2017},

date = {2017-12-01},

journal = {Nat Med},

volume = {23},

number = {12},

pages = {1396--1398},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29519064,

title = {Resolution enhancement in confocal microscopy using Bessel-Gauss beams},

author = {Louis Thibon and Louis E Lorenzo and Michel Piché and Yves De Koninck},

doi = {10.1364/OE.25.002162},

issn = {1094-4087},

year  = {2017},

date = {2017-02-01},

journal = {Opt Express},

volume = {25},

number = {3},

pages = {2162--2177},

abstract = {Laser scanning microscopy is limited in lateral resolution by the diffraction of light. We show that we can obtain twenty percent improvement in the resolution of confocal microscopy using Bessel-Gauss beams with the right pinhole size compared to conventional Gaussian beam based confocal microscopy. Advantages of this strategy include simplicity of installation and use, linear polarization compatibility, possibility to combine it with other resolution enhancement and superresolution strategies. We demonstrate the resolution enhancement capabilities of Bessel-Gauss beams both theoretically and experimentally on nano-spheres and biological tissue samples without any residual artifacts coming from the Bessel-Gauss beam side lobes with a resolution of 0.39λ. We also show that the resolution enhancement of Bessel-Gauss beams yields a better statistical colocalization analysis with fewer false positive results than when using Gaussian beams. We have also used Bessel-Gauss beams of different orders to further improve the resolution by combining them in SLAM microscopy (Switching LAser Modes : Dehez, Optics Express, 2013) achieving a resolution of 0.2λ.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28280406,

title = {Development and Implementation of a Registry of Patients Attending Multidisciplinary Pain Treatment Clinics: The Quebec Pain Registry},

author = {M Choinière and M A Ware and M G Pagé and A Lacasse and H Lanctôt and N Beaudet and A Boulanger and P Bourgault and C Cloutier and L Coupal and Y De Koninck and D Dion and P Dolbec and L Germain and V Martin and P Sarret and Y Shir and M-C Taillefer and B Tousignant and A Trépanier and R Truchon},

doi = {10.1155/2017/8123812},

issn = {1918-1523},

year  = {2017},

date = {2017-01-01},

journal = {Pain Res Manag},

volume = {2017},

pages = {8123812},

abstract = {The Quebec Pain Registry (QPR) is a large research database of patients suffering from various chronic pain (CP) syndromes who were referred to one of five tertiary care centres in the province of Quebec (Canada). Patients were monitored using common demographics, identical clinical descriptors, and uniform validated outcomes. This paper describes the development, implementation, and research potential of the QPR. Between 2008 and 2013, 6902 patients were enrolled in the QPR, and data were collected prior to their first visit at the pain clinic and six months later. More than 90% of them (mean age ± SD: 52.76 ± 4.60, females: 59.1%) consented that their QPR data be used for research purposes. The results suggest that, compared to patients with serious chronic medical disorders, CP patients referred to tertiary care clinics are more severely impaired in multiple domains including emotional and physical functioning. The QPR is also a powerful and comprehensive tool for conducting research in a "real-world" context with 27 observational studies and satellite research projects which have been completed or are underway. It contains data on the clinical evolution of thousands of patients and provides the opportunity of answering important research questions on various aspects of CP (or specific pain syndromes) and its management.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}