Biology subjects

Vialou, V.

Publications and source records attributed to Vialou, V..

6 recordsLinked to original sources

bioRxiv2025

The Role of Insular Anterior Parvalbumin GABAergic Interneurons in Impulsivity-Related and Alcohol-Seeking Behaviors

Alcohol use is a major global health concern, particularly during adolescence, a developmental period characterized by heightened impulsivity, a known risk factor for alcohol misuse. The insular cortex is critically involved in interoceptive processing and impulsivity regulation, and its activity is powerfully shaped by parvalbumin (PV)-expressing GABAergic interneurons. We hypothesized that developmental differences in PV interneuron activity within the insular cortex contribute to impulsivity-related behaviors and alcohol consumption. To investigate this, male C57BL/6 mice were assessed at two developmental stages: adolescence (postnatal day 28) and young adulthood (postnatal day 64). Impulsivity was measured using the Omission-Contingency Learning (OCL) task, while alcohol intake and preference were evaluated using a two-bottle choice paradigm. Adolescent mice displayed higher impulsivity and greater alcohol consumption than adults. Double immunofluorescence labeling (Fos+/NeuN+ and Fos+/PV+) showed that increased impulsivity was associated with reduced activation of PV interneurons in the insular cortex. Chemogenetic activation of PV interneurons in adult PV-Cre mice reduced impulsivity in the OCL task and decreased alcohol intake. These findings indicate that insular PV interneurons play a modulatory role in impulsive behavior and alcohol consumption, suggesting a potential therapeutic target for impulse-control and alcohol-use disorders.

neuroscience↗

bioRxiv2025

Differential Effects of Cocaine Self-Administration Regimens on Incubation of Cocaine Craving and Nucleus Accumbens Neuronal Ensembles Activated by Cocaine-Associated Context

Drug addiction develops in a subset of users following repeated exposure, influenced by biopsychosocial factors. Rodent self-administration protocols, varying in drug access times, are used to study both controlled and compulsive drug-taking behaviors and their neurobiological underpinnings. Drug-associated cues and environmental contexts are well-established triggers for relapse, with susceptibility to these stimuli peaking during early abstinence and remaining elevated, thereby increasing relapse risk. This phenomenon, known as incubation of craving, has been replicated across substances in animal models. The associative learning between drug effects and contextual cues is encoded by neuronal ensembles activated by drug-associated stimuli, driving craving, seeking, and relapse. Neuronal ensembles in the nucleus accumbens (NAcc) are strongly involved in drug seeking, with parvalbumin-expressing fast-spiking interneurons playing a key role in this associative learning process. We investigated activation patterns in the NAcc triggered by cocaine-related cues following restricted- or extended-access self-administration and examined how forced abstinence alters these patterns, contributing to the incubation of cocaine craving. We also analyzed the engagement of parvalbumin-positive interneurons in NAcc neuronal ensembles before and after forced abstinence. Our findings show that the extended access protocol more effectively induced the incubation of cocaine craving. Neuronal activation in the NAcc core increased after thirty days of forced abstinence in both groups, with extended access rats showing consistently higher activation. Forced abstinence also increased NAcc shell activation, with no differences between protocols. NAcc core activation, but not shell, was influenced by cocaine consumption during training. Notably, extended access rats exhibited reduced parvalbumin interneurons activation following thirty days of forced abstinence. Based on these findings, we speculate that the transition from occasional to compulsive drug-taking may be driven by molecular changes in the NAcc core that enhance its responsiveness to drug-related cues. Additionally, the incubation of craving could be linked to impaired inhibitory control of NAcc core medium spiny neurons by PV interneurons.

neuroscience↗

bioRxiv2024

Genetic liability underlying reward-related comorbidity in psychiatric disorders involves the coincident functions of autism-linked ADGRL1 and hevin

Comorbidity between psychiatric traits is thought to involve overlapping pleiotropic effects from sets of genes. Notably, substance abuse is a shared comorbid condition among various neurodevelopmental disorders with externalizing symptoms such as autism spectrum disorder and attention-deficit hyperactivity disorder, thus hinting at the nucleus accumbens (NAc) as a site for predisposition underlying convergence of genetic influences in reward-related comorbidity. Here, we identify the autism-related gene encoding the adhesion G protein-coupled receptor (aGPCR) Latrophilin-1/ADGRL1 as an essential transducer of reward mechanisms in the NAc. We found that ADGRL1 mRNA is ubiquitously expressed throughout major NAc neuronal populations in mice. A mouse model of pan-neuronal Adgrl1 deficiency in the NAc displayed cocaine-seeking impairments in adult individuals denoting its role in drug-induced reinforcement and reward. Connecting molecular pathways of cocaine-induced learning, we uncover that ADGRL1 constitutes a functional receptor for autism-related cocaine effector molecule hevin/SPARCL1. Indeed, hevin interacts with membrane-expressed ADGRL1 and induces its internalization while stabilizing its uncleaved fraction. Moreover, hevin alters the formation of intercellular adhesion contacts mediated by ADGRL1 and Neurexin-1. Importantly, the functional constitutive coupling between ADGRL1 and various G protein pathways is selectively modulated by hevin stimulation with a bias toward Gi3, Gs, and G13 proteins. These findings unveil the dual role of ADGRL1 and hevin as genetic risk factors for both psychiatric disorders and substance abuse to define the molecular etiology of comorbidity.

neuroscience↗

bioRxiv2023

Astrocyte aquaporin mediates a tonic water efflux maintaining brain homeostasis

Brain water homeostasis not only provides a physical protection, but also determines the diffusion of chemical molecules key for information processing and metabolic stability. As a major type of glia in brain parenchyma, astrocytes are the dominant cell type expressing aquaporin water channel. How astrocyte aquaporin contributes to brain water homeostasis in basal physiology remains to be understood. We report that astrocyte aquaporin 4 (AQP4) mediates a tonic water efflux in basal conditions. Acute inhibition of astrocyte AQP4 leads to intracellular water accumulation as optically resolved by fluorescence-translated imaging in acute brain slices, and in vivo by fiber photometry in mobile mice. We then show that aquaporin-mediated constant water efflux maintains astrocyte volume and osmotic equilibrium, astrocyte and neuron Ca2+ signaling, and extracellular space remodeling during optogenetically induced cortical spreading depression. Using diffusion-weighted magnetic resonance imaging (DW-MRI), we observed that in vivo inhibition of AQP4 water efflux heterogeneously disturbs brain water homeostasis in a region-dependent manner. Our data suggest that astrocyte aquaporin, though bidirectional in nature, mediates a tonic water outflow to sustain cellular and environmental equilibrium in brain parenchyma. Significance statementOur brain is immersed, thus protected, in a water environment. It ensures intra- and extracellular molecular diffusion, which is vital for brain function and health. Brain water homeostasis is maintained by dynamic water transport between different cell types. Astrocytes are a main type of glial cell widely distributed in brain parenchyma, expressing the bidirectional aquaporin water channel. Here we show that in basal conditions, aquaporin channel mediates a tonic water efflux from astrocytes. This mechanism maintains astrocyte volume stability, activity-gated brain parenchyma remodeling and brain water homeostasis. Our finding sheds light on how astrocytes regulate water states in the brain, and will help to understand brain allostasis in specific life contexts.

physiology↗

bioRxiv2023

Astrocytes control cocaine-induced synaptic plasticity and reward through the matricellular protein hevin

Drug addiction involves profound modifications of neuronal plasticity in the nucleus accumbens, which may engage various cell types. Here, we report prominent effects of cocaine on calcium signals in astrocytes characterized by in vivo fiber photometry. Astrocyte calcium signals in the nucleus accumbens are sufficient and necessary for the acquisition of cocaine seeking behavior. We identify the astrocyte-secreted matricellular protein hevin as an effector of the action of cocaine and calcium signals on reward and neuronal plasticity.

neuroscience↗

bioRxiv2023

Organic cation transporter 2 contributes to SSRI antidepressant efficacy by controlling tryptophan availability in the brain

Selective serotonin reuptake inhibitors (SSRI) are common first-line treatments for major depression. However, a significant number of depressed patients do not respond adequately to these pharmacological treatments. In the present preclinical study, we demonstrate that organic cation transporter 2 (OCT2), an atypical monoamine transporter, contributes to the effects of SSRI by regulating the routing of the essential amino acid tryptophan to the brain. Contrarily to wild-type mice, OCT2-invalidated mice failed to respond to prolonged fluoxetine treatment in a chronic depression model induced by corticosterone exposure recapitulating core symptoms of depression, i.e., anhedonia, social withdrawal, anxiety, and memory impairment. After corticosterone and fluoxetine treatment, the levels of tryptophan and its metabolites serotonin and kynurenine were decreased in the brain of OCT2 mutant mice compared to wild-type mice and reciprocally tryptophan and kynurenine levels were increased in mutants plasma. OCT2 was detected by immunofluorescence in several structures at the blood-cerebrospinal fluid (CSF) or brain-CSF interface. Tryptophan supplementation during fluoxetine treatment increased brain concentrations of tryptophan in wild-type and OCT2 mutant mice, yet more efficiently in WT than in mutants, while discretely increasing 5-HT concentrations. Importantly, tryptophan supplementation improved the sensitivity to fluoxetine treatment of OCT2 mutant mice, impacting chiefly anhedonia and short-term memory. Western blot analysis showed that glycogen synthase kinase-3{beta} (GSK3{beta}) and mammalian/mechanistic target of rapamycin (mTOR) intracellular signaling was impaired in OCT2 mutant mice brain after corticosterone and fluoxetine treatment and, conversely, tryptophan supplementation recruited selectively the mTOR protein complex 2. This study provides the first evidence of the physiological relevance of OCT2-mediated tryptophan transport, and its biological consequences on serotonin homeostasis in the brain and SSRI efficacy.

neuroscience↗