@article{pmid40404959,

title = {The Tailtag: A multi-mouse tracking system to measure social dynamics in complex environments},

author = {Vincent Coulombe and Arturo Marroquin Rivera and Sadegh Monfared and David-Alexandre Roussel and Quentin Leboulleux and Modesto R Peralta and Benoit Gosselin and Benoit Labonté},

doi = {10.1038/s41386-025-02126-y},

issn = {1740-634X},

year  = {2025},

date = {2025-08-01},

journal = {Neuropsychopharmacology},

volume = {50},

number = {9},

pages = {1336--1345},

abstract = {Despite recent advances, tracking individual movements safely and reliably over extended periods, particularly within complex social groups, remains a challenge. Traditional methods like color coding, tagging, and RFID tracking, while effective, have notable practical limitations. State-of-the-art neural network-based trackers often struggle to maintain individual identities in large groups for more than a few seconds. Fiducial tags such as ArUco codes present a potential solution to enable accurate tracking and identity management. However, their application to large groups of socially interacting mice in complex, enriched environments remain an open challenge. Here, we present the Tailtag system, a novel approach designed to address this challenge. The Tailtag is a non-invasive, safe, and ergonomic tail ring embedded with an ArUco marker allowing to track individual mice in colonies of up to 20 individuals in complex environments for at least seven days without performance degradation or behavioral alteration. We provide a comprehensive parameter optimization guide and practical recommendations for marker selection, for reproducibility across diverse experimental setups. Using data collected from Tailtag-equipped mice, we revealed the formation and evolution of social groups within the colony. Our analysis identified social hub regions within the vivarium where social contacts occur at different frequencies throughout one week of recordings. We quantified interactions and avoidance patterns between specific pairs of mice within the most active social hubs. Overall, our findings indicate that while the zone preferences and peer associations among the mice change over time, certain groups and pairwise interactions consistently form within the social colony.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39821553,

title = {A Novel Statistical Method for Unmasking Sex-Specific Genomics Signatures in Complex Traits},

author = {Samaneh Mansouri and Mélissa Rochette and Benoit Labonté and Qingrun Zhang and Ting-Huei Chen},

doi = {10.1002/gepi.22612},

issn = {1098-2272},

year  = {2025},

date = {2025-01-01},

journal = {Genet Epidemiol},

volume = {49},

number = {1},

pages = {e22612},

abstract = {Genotype-phenotype association studies have advanced our understanding of complex traits but often overlook sex-specific genetic signals. The growing awareness of sex-specific influences on human traits and diseases necessitates tailored statistical methodologies to dissect these genetic intricacies. Rare genetic variants play a significant role in disease development, often exhibiting stronger per-allele effects than common variants. In sex-dimorphic analysis, traits are viewed as having two sex-specific subsets rather than being uniformly defined. Existing methods for gene-based analysis of rare variants across multiple traits can identify shared genetic signals but cannot reveal the specific subsets from which significant signals originate. This means that when a significant signal is detected, it remains unclear whether it arises from the male samples, female samples, or both. To address this limitation, we propose SubsetRV, a new methodology capable of identifying genes associated with specific traits or diseases in males, females, or both. SubsetRV can also be applied to broader applications in multiple traits analysis. Simulation studies have demonstrated SubsetRV's reliability, and real data analysis on bipolar disorder and schizophrenia has revealed potential sex-specific genetic signals. SubsetRV offers a valuable tool for identifying sex-specific genetic candidates, aiding in understanding disease mechanisms. An R package for SubsetRV is available on GitHub. It can be accessed directly through this link: https://github.com/Mansouri-S/SubsetRV.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39613383,

title = {You Are What You Eat, and You Behave Accordingly: How B12 Influences the Occurrence of Neuropsychiatric Disorders via Epigenetic Mechanisms},

author = {Arturo Marroquin Rivera and Benoit Labonté},

doi = {10.1016/j.biopsych.2024.10.010},

issn = {1873-2402},

year  = {2025},

date = {2025-01-01},

journal = {Biol Psychiatry},

volume = {97},

number = {1},

pages = {2--4},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39164106,

title = {Chronic Social Defeat Stress Induces Pathway-Specific Adaptations at Lateral Habenula Neuronal Outputs},

author = {Jose Cesar Hernandez Silva and Nikola Pausic and Arturo Marroquin Rivera and Benoît Labonté and Christophe D Proulx},

doi = {10.1523/JNEUROSCI.2082-23.2024},

issn = {1529-2401},

year  = {2024},

date = {2024-09-01},

journal = {J Neurosci},

volume = {44},

number = {39},

abstract = {The lateral habenula (LHb) has emerged as a pivotal brain region implicated in depression, displaying hyperactivity in human and animal models of depression. While the role of LHb efferents in depressive disorders has been acknowledged, the specific synaptic alterations remain elusive. Here, employing optogenetics, retrograde tracing, and ex vivo whole-cell patch-clamp techniques, we investigated synaptic transmission in male mice subjected to chronic social defeat stress (CSDS) at three major LHb neuronal outputs: the dorsal raphe nucleus (DRN), the ventral tegmental area (VTA), and the rostromedial tegmental nucleus (RMTg). Our findings uncovered distinct synaptic adaptations in LHb efferent circuits in response to CSDS. Specifically, CSDS induced in susceptible mice postsynaptic potentiation and postsynaptic depression at the DRN and VTA neurons, respectively, receiving excitatory inputs from the LHb, while CSDS altered presynaptic transmission at the LHb terminals in RMTg in both susceptible and resilient mice. Moreover, whole-cell recordings at projection-defined LHb neurons indicate decreased spontaneous activity in VTA-projecting LHb neurons, accompanied by an imbalance in excitatory-inhibitory inputs at the RMTg-projecting LHb neurons. Collectively, these novel findings underscore the circuit-specific alterations in LHb efferents following chronic social stress, shedding light on potential synaptic adaptations underlying stress-induced depressive-like states.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38216730,

title = {Immune-related transcriptomic and epigenetic reconfiguration in BV2 cells after lipopolysaccharide exposure: an in vitro omics integrative study},

author = {Arturo Marroquín-Rivera and Chenqi Zhao and André Moreira Pessoni and Juliette Bherer and Samaneh Mansouri and Arnaud Droit and Benoit Labonté},

doi = {10.1007/s00011-023-01830-z},

issn = {1420-908X},

year  = {2024},

date = {2024-02-01},

journal = {Inflamm Res},

volume = {73},

number = {2},

pages = {211--225},

abstract = {BACKGROUND: Molecular alterations affecting microglia have been consistently associated with the inflammatory response. These cells can have pro- or anti-inflammatory activity, phenotypes thought to be regulated by epigenetic mechanisms. Still, little is known about the details on how epigenetic marks regulate the expression of genes in the context of an inflammatory response.nnMETHODS: Through CUT&RUN, we profiled four genome-wide histone marks (HM) (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) in lipopolysaccharide-exposed cells and compared their distributions to control cells. Transcriptomic profiles were determined through RNA-seq and differentially expressed genes were identified and contrasted with the epigenetic landscapes. Other downstream analyses were also included in this study.nnRESULTS: Our results illustrate an effectively induced M1 phenotype in microglial cells derived from LPS exposure. We observed differential bound regions associated with the genes classically involved in the inflammatory response in the expected direction according to each histone modification. Consistently, our transcriptomic analysis yielded a conspicuous illustration of the LPS-induced immune activity showing the up-regulation of Nf-κB-induced mRNAs (TNF-α, nfκbiz, nfκbia) and other important genes (Marco, Il-6, etc.). Furthermore, we integrated both omics profiles and identified an important reconfiguration of the genome induced by LPS. The latter was depicted by 8 different chromatin states that changed between conditions and that associated with unique clusters of differentially expressed genes, which not only represented regulatory elements, but also underlined distinct biological functions (inhibition of morphogenesis; changes in metabolism, homeostasis, and cytokine regulation; activation of the inflammatory response).nnCONCLUSION: This study exhibits important differences in the distribution of histone modifications in treated and control BV2 cells, constituting an epigenetic reconfiguration that leads to the inflammatory response. Also, it highlights the importance of these marks' regulatory role in gene expression and provides possible targets for further studies in the context of inflammation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38026162,

title = {Hypothalamic neuronal outputs transmit sensorimotor signals at the onset of locomotor initiation},

author = {Ekaterina Martianova and Renata Sadretdinova and Alicia Pageau and Nikola Pausic and Tommy Doucet Gentiletti and Danahé Leblanc and Arturo Marroquin Rivera and Benoît Labonté and Christophe D Proulx},

doi = {10.1016/j.isci.2023.108328},

issn = {2589-0042},

year  = {2023},

date = {2023-11-01},

journal = {iScience},

volume = {26},

number = {11},

pages = {108328},

abstract = {The lateral hypothalamus (LH) plays a critical role in sensory integration to organize behavior responses. However, how projection-defined LH neuronal outputs dynamically transmit sensorimotor signals to major downstream targets to organize behavior is unknown. Here, using multi-fiber photometry, we show that three major LH neuronal outputs projecting to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and lateral habenula (LHb) exhibit significant coherent activity in mice engaging sensory-evoked or self-initiated motor responses. Increased activity at LH axon terminals precedes movement initiation during active coping responses and the activity of serotonin neurons and dopamine neurons. The optogenetic activation of LH axon terminals in either of the DRN, VTA, or LHb was sufficient to increase motor initiation but had different effects on passive avoidance and sucrose consumption. Our findings support the complementary role of three projection-defined LH neuronal outputs in the transmission of sensorimotor signals to major downstream regions at movement onset.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37884562,

title = {Transcriptional dissection of symptomatic profiles across the brain of men and women with depression},

author = {Samaneh Mansouri and André M Pessoni and Arturo Marroquín-Rivera and Eric M Parise and Carol A Tamminga and Gustavo Turecki and Eric J Nestler and Ting-Huei Chen and Benoit Labonté},

doi = {10.1038/s41467-023-42686-5},

issn = {2041-1723},

year  = {2023},

date = {2023-10-01},

journal = {Nat Commun},

volume = {14},

number = {1},

pages = {6835},

abstract = {Major depressive disorder (MDD) is one of the most important causes of disability worldwide. While recent work provides insights into the molecular alterations in the brain of patients with MDD, whether these molecular signatures can be associated with the expression of specific symptom domains remains unclear. Here, we identified sex-specific gene modules associated with the expression of MDD, combining differential gene expression and co-expression network analyses in six cortical and subcortical brain regions. Our results show varying levels of network homology between males and females across brain regions, although the associations between these structures and the expression of MDD remain highly sex specific. We refined these associations to several symptom domains and identified transcriptional signatures associated with distinct functional pathways, including GABAergic and glutamatergic neurotransmission, metabolic processes and intracellular signal transduction, across brain regions associated with distinct symptomatic profiles in a sex-specific fashion. In most cases, these associations were specific to males or to females with MDD, although a subset of gene modules associated with common symptomatic features in both sexes were also identified. Together, our findings suggest that the expression of distinct MDD symptom domains associates with sex-specific transcriptional structures across brain regions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36075764,

title = {Comparative Transcriptional Analyses in the Nucleus Accumbens Identifies RGS2 as a Key Mediator of Depression-Related Behavior},

author = {Alexia V Williams and Catherine J Peña and Stephanie Ramos-Maciel and Abigail Laman-Maharg and Evelyn Ordoñez-Sanchez and Monica Britton and Blythe Durbin-Johnson and Matt Settles and Rebecca Hao and Sae Yokoyama and Christine Xu and Pei X Luo and Tjien Dwyer and Shanu Bhela and Alexis M Black and Benoit Labonté and Randal Alex Serafini and Anne Ruiz and Rachael L Neve and Venetia Zachariou and Eric J Nestler and Brian C Trainor},

doi = {10.1016/j.biopsych.2022.06.030},

issn = {1873-2402},

year  = {2022},

date = {2022-12-01},

journal = {Biol Psychiatry},

volume = {92},

number = {12},

pages = {942--951},

abstract = {BACKGROUND: Major depressive disorder is one of the most commonly diagnosed mental illnesses worldwide, with a higher prevalence in women than in men. Although currently available pharmacological therapeutics help many individuals, they are not effective for most. Animal models have been important for the discovery of molecular alterations in stress and depression, but difficulties in adapting animal models of depression for females has impeded progress in developing novel therapeutic treatments that may be more efficacious for women.nnMETHODS: Using the California mouse social defeat model, we took a multidisciplinary approach to identify stress-sensitive molecular targets that have translational relevance for women. We determined the impact of stress on transcriptional profiles in male and female California mouse nucleus accumbens (NAc) and compared these results with data from postmortem samples of the NAc from men and women diagnosed with major depressive disorder.nnRESULTS: Our cross-species computational analyses identified Rgs2 (regulator of G protein signaling 2) as a transcript downregulated by social defeat stress in female California mice and in women with major depressive disorder. RGS2 plays a key role in signal regulation of neuropeptide and neurotransmitter receptors. Viral vector-mediated overexpression of Rgs2 in the NAc restored social approach and sucrose preference in stressed female California mice.nnCONCLUSIONS: These studies show that Rgs2 acting in the NAc has functional properties that translate to changes in anxiety- and depression-related behavior. Future studies should investigate whether targeting Rgs2 represents a novel target for treatment-resistant depression in women.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35592639,

title = {Sex-Specific Brain Transcriptional Signatures in Human MDD and Their Correlates in Mouse Models of Depression},

author = {Maureen Touchant and Benoit Labonté},

doi = {10.3389/fnbeh.2022.845491},

issn = {1662-5153},

year  = {2022},

date = {2022-01-01},

journal = {Front Behav Neurosci},

volume = {16},

pages = {845491},

abstract = {Major depressive disorder (MDD) is amongst the most devastating psychiatric conditions affecting several millions of people worldwide every year. Despite the importance of this disease and its impact on modern societies, still very little is known about the etiological mechanisms. Treatment strategies have stagnated over the last decades and very little progress has been made to improve the efficiency of current therapeutic approaches. In order to better understand the disease, it is necessary for researchers to use appropriate animal models that reproduce specific aspects of the complex clinical manifestations at the behavioral and molecular levels. Here, we review the current literature describing the use of mouse models to reproduce specific aspects of MDD and anxiety in males and females. We first describe some of the most commonly used mouse models and their capacity to display unique but also shared features relevant to MDD. We then transition toward an integral description, combined with genome-wide transcriptional strategies. The use of these models reveals crucial insights into the molecular programs underlying the expression of stress susceptibility and resilience in a sex-specific fashion. These studies performed on human and mouse tissues establish correlates into the mechanisms mediating the impact of stress and the extent to which different mouse models of chronic stress recapitulate the molecular changes observed in depressed humans. The focus of this review is specifically to highlight the sex differences revealed from different stress paradigms and transcriptional analyses both in human and animal models.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34693223,

title = {Methylation of the tyrosine hydroxylase gene is dysregulated by cocaine dependence in the human striatum},

author = {Kathryn Vaillancourt and Gang G Chen and Laura Fiori and Gilles Maussion and Volodymyr Yerko and Jean-François Théroux and Carl Ernst and Benoit Labonté and Erin Calipari and Eric J Nestler and Corina Nagy and Naguib Mechawar and Deborah C Mash and Gustavo Turecki},

doi = {10.1016/j.isci.2021.103169},

issn = {2589-0042},

year  = {2021},

date = {2021-10-01},

journal = {iScience},

volume = {24},

number = {10},

pages = {103169},

abstract = {Cocaine dependence is a chronic, relapsing disorder caused by lasting changes in the brain. Animal studies have identified cocaine-related alterations in striatal DNA methylation; however, it is unclear how methylation is related to cocaine dependence in humans. We generated methylomic profiles of the nucleus accumbens using human postmortem brains from a cohort of individuals with cocaine dependence and healthy controls (n = 25 per group). We found hypermethylation in a cluster of CpGs within the gene body of tyrosine hydroxylase  containing a putative binding site for the early growth response 1 (EGR1) transcription factor, which is hypermethylated in the caudate nucleus of cocaine-dependent individuals. We replicated this finding and found it to be specific to striatal neuronal nuclei. Furthermore, this locus demonstrates enhancer activity which is attenuated by methylation and enhanced by EGR1 overexpression. These results suggest that cocaine dependence alters the epigenetic regulation of dopaminergic signaling genes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}