Publications du Neurocentre Magendie

Les publications

IF du Neurocentre

777 publications

* equal contribution

08/07/2020 | Nature   IF 42.8
Glucose metabolism links astroglial mitochondria to cannabinoid effects.


29/06/2020 | Molecular Brain   IF 4.7


29/06/2020 | Aging Cell   IF 7.2


09/06/2020 | Cell Rep   IF 8.1
Vangl2 in the Dentate Network Modulates Pattern Separation and Pattern Completion.


09/06/2020 | Neuroendocrinology   IF 4.3


06/2020 | hepatol commun


22/05/2020 | Nutrients   IF 4.5


18/05/2020 | Nat Commun   IF 12.1


05/2020 | sci adv   IF 13.1


25/04/2020 | J Clin Endocrinol Metab   IF 5.4


Quarta C, Cota D


20/04/2020 | Nat Commun   IF 12.1


03/03/2020 | Cell Metab   IF 21.6


03/2020 |
Juvenile mild traumatic brain injury elicits distinct spatiotemporal astrocyte responses.


02/2020 | Neurosci Biobehav Rev   IF 8.3
What we can learn from a genetic rodent model about autism.


07/01/2020 | elife   IF 7.1


07/01/2020 | Neuron   IF 14.4


01/2020 | addiction   IF 6.3
The relevance of animal models of addiction.
Deroche-Gamonet V

2020 | Handbook of Behavioral Neuroscience
Beyeler A, Dabrowska J


09/12/2019 | J Neurosci Methods   IF 2.2


02/11/2019 | Neuroscience   IF 3.1
Quarta C, Fioramonti X, Cota D


11/2019 | neurobiol stress   IF 7.2
Neurobiological links between stress and anxiety.


24/10/2019 | Psychoneuroendocrinology   IF 4.7


17/10/2019 | Behav Brain Res   IF 3


21/09/2019 | Nutrients   IF 4.5


11/08/2019 | j pers   IF 3.7



02/07/2019 | Curr Biol   IF 9.6
CB1 Receptors in the Anterior Piriform Cortex Control Odor Preference Memory.


25/06/2019 | Cell Rep   IF 8.1


22/05/2019 | J Neurosci   IF 5.7


12/04/2019 | Science   IF 41.8
Perspective - Do antidepressants restore lost synapses?
Beyeler A

02/04/2019 | J Clin Invest   IF 11.9


08/03/2019 | Nat Commun   IF 12.1
Deciphering the complex role of thrombospondin-1 in glioblastoma development.
Daubon T, Leon C, Clarke K, Andrique L, Salabert L, Darbo E, Pineau R, Guerit S, Maitre M, Dedieu S, Jeanne A, Bailly S, Feige JJ, Miletic H, Rossi M, Bello L, Falciani F, Bjerkvig R, Bikfalvi A

We undertook a systematic study focused on the matricellular protein Thrombospondin-1 (THBS1) to uncover molecular mechanisms underlying the role of THBS1 in glioblastoma (GBM) development. THBS1 was found to be increased with glioma grades. Mechanistically, we show that the TGFbeta canonical pathway transcriptionally regulates THBS1, through SMAD3 binding to the THBS1 gene promoter. THBS1 silencing inhibits tumour cell invasion and growth, alone and in combination with anti-angiogenic therapy. Specific inhibition of the THBS1/CD47 interaction using an antagonist peptide decreases cell invasion. This is confirmed by CD47 knock-down experiments. RNA sequencing of patient-derived xenograft tissue from laser capture micro-dissected peripheral and central tumour areas demonstrates that THBS1 is one of the gene with the highest connectivity at the tumour borders. All in all, these data show that TGFbeta1 induces THBS1 expression via Smad3 which contributes to the invasive behaviour during GBM expansion. Furthermore, tumour cell-bound CD47 is implicated in this process.

07/03/2019 | JCI Insight   IF 6.2
The motivation for exercise over palatable food is dictated by cannabinoid type-1 receptors.
Muguruza C, Redon B, Fois GR, Hurel I, Scocard A, Nguyen C, Stevens C, Soria-Gomez E, Varilh M, Cannich A, Daniault J, Busquets-Garcia A, Pelliccia T, Caille S, Georges F, Marsicano G, Chaouloff F

The lack of intrinsic motivation to engage in, and adhere to, physical exercise has major health consequences. However, the neurobiological bases of exercise motivation are still unknown. This study aimed at examining whether the endocannabinoid system (ECS) is involved in this process. To do so, we developed an operant conditioning paradigm wherein mice unlocked a running wheel with nose pokes. Using pharmacological tools and conditional mutants for cannabinoid type-1 (CB1) receptors, we provide evidence that CB1 receptors located on GABAergic neurons are both necessary and sufficient to positively control running motivation. Conversely, this receptor population proved dispensable for the modulation of running duration per rewarded sequence. Although the ECS mediated the motivation for another reward, namely palatable food, such a regulation was independent from CB1 receptors on GABAergic neurons. In addition, we report that the lack of CB1 receptors on GABAergic neurons decreases the preference for running over palatable food when mice were proposed an exclusive choice between the two rewards. Beyond providing a paradigm that enables motivation processes for exercise to be dissected either singly or in concurrence, this study is the first to our knowledge to identify a neurobiological mechanism that might contribute to sedentary behavior.

24/01/2019 | Neurobiol Dis   IF 5.3
Cannabinoid type-1 receptor blockade restores neurological phenotypes in two models for Down syndrome.
Navarro-Romero A, Vazquez-Oliver A, Gomis-Gonzalez M, Garzon-Montesinos C, Falcon-Moya R, Pastor A, Martin-Garcia E, Pizarro N, Busquets-Garcia A, Revest JM, Piazza PV, Bosch F, Dierssen M, de la Torre R, Rodriguez-Moreno A, Maldonado R, Ozaita A

Intellectual disability is the most limiting hallmark of Down syndrome, for which there is no gold-standard clinical treatment yet. The endocannabinoid system is a widespread neuromodulatory system involved in multiple functions including learning and memory processes. Alterations of this system contribute to the pathogenesis of several neurological and neurodevelopmental disorders. However, the involvement of the endocannabinoid system in the pathogenesis of Down syndrome has not been explored before. We used the best-characterized preclinical model of Down syndrome, the segmentally trisomic Ts65Dn model. In male Ts65Dn mice, cannabinoid type-1 receptor (CB1R) expression was enhanced and its function increased in hippocampal excitatory terminals. Knockdown of CB1R in the hippocampus of male Ts65Dn mice restored hippocampal-dependent memory. Concomitant with this result, pharmacological inhibition of CB1R restored memory deficits, hippocampal synaptic plasticity and adult neurogenesis in the subgranular zone of the dentate gyrus. Notably, the blockade of CB1R also normalized hippocampal-dependent memory in female Ts65Dn mice. To further investigate the mechanisms involved, we used a second transgenic mouse model overexpressing a single gene candidate for Down syndrome cognitive phenotypes, the dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A). CB1R pharmacological blockade similarly improved cognitive performance, synaptic plasticity and neurogenesis in transgenic male Dyrk1A mice. Our results identify CB1R as a novel druggable target potentially relevant for the improvement of cognitive deficits associated with Down syndrome.

07/01/2019 | Cold Spring Harb Perspect Med   IF 6
Development and Patterning of the Cochlea: From Convergent Extension to Planar Polarity.
Montcouquiol M, Kelley MW

Within the mammalian cochlea, sensory hair cells and supporting cells are aligned in curvilinear rows that extend along the length of the tonotopic axis. In addition, all of the cells within the epithelium are uniformly polarized across the orthogonal neural-abneural axis. Finally, each hair cell is intrinsically polarized as revealed by the presence of an asymmetrically shaped and apically localized stereociliary bundle. It has been known for some time that many of the developmental processes that regulate these patterning events are mediated, to some extent, by the core planar cell polarity (PCP) pathway. This article will review more recent work demonstrating how components of the PCP pathway interact with cytoskeletal motor proteins to regulate cochlear outgrowth. Finally, a signaling pathway originally identified for its role in asymmetric cell divisions has recently been shown to mediate several aspects of intrinsic hair cell polarity, including kinocilia migration, bundle shape, and elongation.

2019 | Current Opinion in Behavioral Sciences   IF 4
Valence Coding in Amygdala Circuits
Pignatelli M, Beyeler A

The neural mechanisms underlying emotional valence are at the interface between perception and action, integrating inputs from the external environment with past experiences to guide the behavior of an organism. Depending on the positive or negative valence assigned to an environmental stimulus, the organism will approach or avoid the source of the stimulus. Multiple convergent studies have demonstrated that the amygdala complex is a critical node of the circuits assigning valence. Here we examine the current progress in identifying valence coding properties of neural populations in different nuclei of the amygdala, based on their activity, connectivity, and gene expression profile.

2019 | front pharmacol   IF 4.2
Beyond the Activity-Based Anorexia Model: Reinforcing Values of Exercise and Feeding Examined in Stressed Adolescent Male and Female Mice.
Hurel I, Redon B, Scocard A, Malezieux M, Marsicano G, Chaouloff F

Anorexia nervosa (AN), mostly observed in female adolescents, is the most fatal mental illness. Its core is a motivational imbalance between exercise and feeding in favor of the former. The most privileged animal model of AN is the 'activity-based anorexia' (ABA) model wherein partly starved rodents housed with running wheels exercise at the expense of feeding. However, the ABA model bears face and construct validity limits, including its inability to specifically assess running motivation and feeding motivation. As infant/adolescent trauma is a precipitating factor in AN, this study first analyzed post-weaning isolation rearing (PWIR) impacts on body weights and wheel-running performances in female mice exposed to an ABA protocol. Next, we studied through operant conditioning protocols i) whether food restriction affects in a sex-dependent manner running motivation before ii) investigating how PWIR and sex affect running and feeding drives under ad libitum fed conditions and food restriction. Besides amplifying ABA-elicited body weight reductions, PWIR stimulated wheel-running activities in anticipation of feeding in female mice, suggesting increased running motivation. To confirm this hypothesis, we used a cued-reward motivated instrumental task wherein wheel-running was conditioned by prior nose poke responses. It was first observed that food restriction increased running motivation in male, but not female, mice. When fed grouped and PWIR mice were tested for their running and palatable feeding drives, all mice, excepted PWIR males, displayed increased nose poke responses for running over feeding. This was true when rewards were proposed alone or within a concurrent test. The increased preference for running over feeding in fed females did not extend to running performances (time, distance) during each rewarded sequence, confirming that motivation for, and performance during, running are independent entities. With food restriction, mice displayed a sex-independent increase in their preference for feeding over running in both group-housed and PWIR conditions. This study shows that the ABA model does not specifically capture running and feeding drives, i.e. components known to be affected in AN.

2019 | Front Behav Neurosci   IF 2.5
Varenicline Targets the Reinforcing-Enhancing Effect of Nicotine on Its Associated Salient Cue During Nicotine Self-administration in the Rat.
Garcia-Rivas V, Fiancette JF, Cannella N, Carbo-Gas M, Renault P, Tostain J, Deroche-Gamonet V

Nicotine is acknowledged as the key addictive compound of tobacco. Varenicline (Champix((R)) or Chantix((R))), mainly acting as a partial agonist at the alpha4beta2 nicotinic receptor, is an approved smoking cessation pharmacotherapy, although with efficacy limited to a portion of smokers. Smokers differ in the motives that drive their drug seeking and Varenicline might be more efficient in some groups more than others. Studies in rodents revealed that nicotine-seeking is strongly supported by complex interactions between nicotine and environmental cues, and notably the ability of nicotine to enhance the reinforcing properties of salient environmental stimuli. It is not yet understood whether the decrease of nicotine-seeking by acute Varenicline in rats results from antagonism of the primary reinforcing effects of nicotine, of the reinforcement-enhancing effect of nicotine on cues, or of a combination of both. Thanks to a protocol that allows assessment of the reinforcement-enhancing effect of nicotine on cues during self-administration in rats, we showed that Varenicline targets both nicotine reinforcing effects and reinforcement-enhancing effect of nicotine on cues. Importantly, individual variations in the latter determined the amplitude of acute Varenicline-induced decrease in seeking. These results suggest that Varenicline might be more beneficial in smokers who are more sensitive to nicotine effects on surrounding stimuli.

20/12/2018 | j neuroinflammation   IF 5.8


23/11/2018 | Int J Mol Sci   IF 4.6
Heterogeneity in Colorectal Cancer: A Challenge for Personalized Medicine?
Molinari C, Marisi G, Passardi A, Matteucci L, De Maio G, Ulivi P

High inter-patient variability and high spatial heterogeneity are features of colorectal cancer (CRC). This may influence the molecular characterization of tumor tissue, now mandatory for patients with metastatic CRC who are candidates for treatment with an anti-EGFR mAb, as false-negative results can occur, leading to non optimal therapy. Moreover, temporal molecular heterogeneity during treatment is known to influence the response to therapy and prognosis. We present a literature overview of advances made in characterizing molecular heterogeneity in CRC, underlining that the analysis of liquid biopsy could represent an efficient non-invasive tool to overcome the problem. We believe that understanding CRC heterogeneity is fundamental for a more accurate diagnosis, for selecting the best targets to ensure prolonged antitumor response, and for monitoring minimal residual disease and the onset of resistance to therapy, all essential components of successful personalized treatment.

20/11/2018 | ann surg   IF 10.1
Oea Signaling Pathways and the Metabolic Benefits of Vertical Sleeve Gastrectomy.


07/11/2018 | Nature   IF 42.8
Vander Weele CM, Siciliano CA, Matthews GA, Namburi P, Izadmehr EM, Espinel IC, Nieh EH, Schut EHS, Padilla-Coreano N, Burgos-Robles A, Chang CJ, Kimchi EY, Beyeler A, Wichmann R, Wildes CP, Tye KM

Dopamine modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioural functions(1,2); however, the precise circuit computations remain unknown. One potentially unifying model by which dopamine may underlie a diversity of functions is by modulating the signal-to-noise ratio in subpopulations of mPFC neurons(3-6), where neural activity conveying sensory information (signal) is amplified relative to spontaneous firing (noise). Here we demonstrate that dopamine increases the signal-to-noise ratio of responses to aversive stimuli in mPFC neurons projecting to the dorsal periaqueductal grey (dPAG). Using an electrochemical approach, we reveal the precise time course of pinch-evoked dopamine release in the mPFC, and show that mPFC dopamine biases behavioural responses to aversive stimuli. Activation of mPFC-dPAG neurons is sufficient to drive place avoidance and defensive behaviours. mPFC-dPAG neurons display robust shock-induced excitations, as visualized by single-cell, projection-defined microendoscopic calcium imaging. Finally, photostimulation of dopamine terminals in the mPFC reveals an increase in the signal-to-noise ratio in mPFC-dPAG responses to aversive stimuli. Together, these data highlight how dopamine in the mPFC can selectively route sensory information to specific downstream circuits, representing a potential circuit mechanism for valence processing.

11/2018 | Mol Psychiatry   IF 12.4
CaMKIIbeta regulates nucleus-centrosome coupling in locomoting neurons of the developing cerebral cortex.
Nicole O, Bell DM, Leste-Lasserre T, Doat H, Guillemot F, Pacary E

11/2018 | Mol Psychiatry   IF 12.4
A novel role for CAMKIIbeta in the regulation of cortical neuron migration: implications for neurodevelopmental disorders.

Perturbation of CaMKIIbeta expression has been associated with multiple neuropsychiatric diseases, highlighting CaMKIIbeta as a gene of interest. Yet, in contrast to CaMKIIalpha, the specific functions of CaMKIIbeta in the brain remain poorly explored. Here, we reveal a novel function for this CaMKII isoform in vivo during neuronal development. By using in utero electroporation, we show that CaMKIIbeta is an important regulator of radial migration of projection neurons during cerebral cortex development. Knockdown of CaMKIIbeta causes accelerated migration of nascent pyramidal neurons, whereas overexpression of CaMKIIbeta inhibits migration, demonstrating that precise regulation of CaMKIIbeta expression is required for correct neuronal migration. More precisely, CaMKIIbeta controls the multipolar-bipolar transition in the intermediate zone and locomotion in the cortical plate through its actin-binding and -bundling activities. In addition, our data indicate that a fine-tuned balance between CaMKIIbeta and cofilin activities is necessary to ensure proper migration of cortical neurons. Thus, our findings define a novel isoform-specific function for CaMKIIbeta, demonstrating that CaMKIIbeta has a major biological function in the developing brain.

16/10/2018 | Acta Neuropathol Commun   IF 6.3


10/2018 | Curr Opin Neurobiol   IF 6.3
Neuronal coding mechanisms mediating fear behavior.
Rozeske RR, Herry C


23/09/2018 | Exp Neurol   IF 4.7


In nonhuman mammals and in particular in rodents, most granule neurons of the dentate gyrus (DG) are generated during development and yet little is known about their properties compared with adult-born neurons. Although it is generally admitted that these populations are morphologically indistinguishable once mature, a detailed analysis of developmentally born neurons is lacking. Here, we used in vivo electroporation to label dentate granule cells (DGCs) generated in mouse embryos (E14.5) or in neonates (P0) and followed their morphological development up to 6 months after birth. By comparison with mature retrovirus-labeled DGCs born at weaning (P21) or young adult (P84) stages, we provide the evidence that perinatally born neurons, especially embryonically born cells, are morphologically distinct from later-born neurons and are thus easily distinguishable. In addition, our data indicate that semilunar and hilar GCs, 2 populations in ectopic location, are generated during the embryonic and the neonatal periods, respectively. Thus, our findings provide new insights into the development of the different populations of GCs in the DG and open new questions regarding their function in the brain.

23/08/2018 | Neuron   IF 14.4
Hippocampal CB1 Receptors Control Incidental Associations.
Busquets-Garcia A, Oliveira da Cruz JF, Terral G, Zottola ACP, Soria-Gomez E, Contini A, Martin H, Redon B, Varilh M, Ioannidou C, Drago F, Massa F, Fioramonti X, Trifilieff P, Ferreira G, Marsicano G

By priming brain circuits, associations between low-salience stimuli often guide future behavioral choices through a process known as mediated or inferred learning. However, the precise neurobiological mechanisms of these incidental associations are largely unknown. Using sensory preconditioning procedures, we show that type 1 cannabinoid receptors (CB1R) in hippocampal GABAergic neurons are necessary and sufficient for mediated but not direct learning. Deletion and re-expression of CB1R in hippocampal GABAergic neurons abolishes and rescues mediated learning, respectively. Interestingly, paired presentations of low-salience sensory cues induce a specific protein synthesis-dependent enhancement of hippocampal CB1R expression and facilitate long-term synaptic plasticity at inhibitory synapses. CB1R blockade or chemogenetic manipulations of hippocampal GABAergic neurons upon preconditioning affect incidental associations, as revealed by impaired mediated learning. Thus, CB1R-dependent control of inhibitory hippocampal neurotransmission mediates incidental associations, allowing future associative inference, a fundamental process for everyday life, which is altered in major neuropsychiatric diseases.