Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development

How the vascular and neural compartment cooperate to achieve such a complex and highly specialized structure as the central nervous system is still unclear. Here, we reveal a crosstalk between motor neurons (MNs) and endothelial cells (ECs), necessary for the coordinated development of MNs. By analyzing cell-to-cell interaction profiles of the mouse developing spinal cord, we uncovered semaphorin 3C (Sema3C) and PlexinD1 as a communication axis between MNs and ECs. Using cell-specific knockout mice and in vitro assays, we demonstrate that removal of Sema3C in MNs, or its receptor PlexinD1 in ECs, results in premature and aberrant vascularization of MN columns. Those vascular defects impair MN axon exit from the spinal cord. Impaired PlexinD1 signaling in ECs also causes MN maturation defects at later stages. This study highlights the importance of a timely and spatially controlled communication between MNs and ECs for proper spinal cord development

Cent scientifiques répliquent à SEA (Suppression des Expériences sur l’Animal vivant) et dénoncent sa désinformation

La lutte contre la maltraitance animale est sans conteste une cause moralement juste. Mais elle ne justifie en rien la désinformation à laquelle certaines associations qui s’en réclament ont recours pour remettre en question l’usage de l’expérimentation animale en recherche

Circuits neuronaux du tronc cérébral impliqués dans la régulation des états de vigilance (distribution et rôle des récepteurs 5-HT1A)

Le déclenchement du sommeil paradoxal (SP) est assuré par des structures localisées dans le tronc cérébral. Schématiquement, l apparition du SP serait la conséquence à la fois de l activation de plusieurs ensembles neuronaux exécutifs, SP-ON , et de l inactivation de systèmes dits permissifs , SP-OFF , dont l arrêt facilite l expression des structures exécutives. Parmi ces derniers, les neurones sérotoninergiques (5-HT) des noyaux du Raphé, situés dans le tronc cérébral, ont une position stratégique pour exercer leur influence sur le SP. En outre, un déséquilibre du système 5-HT s accompagne souvent de troubles du SP, et la prise d antidépresseurs inhibiteurs de la recapture de la 5-HT (ISRS), ayant pour effet d augmenter la 5-HT cérébrale, provoque un déficit important en SP. Le système 5-HT pourrait donc jouer un rôle clef dans la modulation du SP; néanmoins, on ignore encore sur quelles structures et par quels mécanismes s exerce son influence. Les récepteurs 5-HT1A (R5-HT1A) ont une action déterminante dans cette influence. Leur activation, par injection systémique d agonistes 5-HT1A, conduit à une forte réduction des quantités de SP concomitante d une augmentation de l éveil. Cependant, nous ne connaissons pas la localisation précise des récepteurs impliqués dans ces effets. Dans ce contexte, j ai entrepris de disséquer les mécanismes d action de la 5-HT au travers des R5-HT1A dans le tronc cérébral chez la souris. Mon travail s est organisé en deux volets : le premier, par une approche anatomique, concerne la caractérisation des populations neuronales du tronc cérébral exprimant le R5-HT1A, susceptibles d être impliquées dans l éveil et le sommeil paradoxal. La caractérisation anatomique des populations neuronales du tronc cérébral font apparaître des influences multiples des R5-HT1A sur la régulation de l éveil et du SP en impliquant exclusivement des systèmes sérotoninergiques, GABAergiques et glutamatergiques. En tenant compte du schéma actuel de régulation du SP, le noyau GABAergique du DTg, qui présente une forte densité de R5-HT1A et est connecté aux réseaux d éveil, apparaissait comme une cible pertinente à étudier dans le cadre des influences sérotoninergiques médiées par les R5-HT1A sur les états de vigilance. Cette étude représente le deuxième volet de mon travail. Par une approche fonctionnelle, à savoir des injections locales de ligands des R5-HT1A combinées à l enregistrement du sommeil, nous avons évalué le rôle de ces récepteurs au niveau du noyau dorsal tegmental (DTg), potentiellement régulateur de l éveil et du SP. Ces injections locales ont entraîné une inhibition significative du SP en jouant possiblement sur les mécanismes de déclenchement, suggérant que le DTg interviendrait dans l initiation du SP. Dans l ensemble, ce travail a ouvert de nombreuses perspectives concernant la caractérisation de nouvelles structures du tronc cérébral comme acteurs de la régulation des états de vigilance. Il a notamment été montré qu une étude anatomique de la nature et des connexions des systèmes neuronaux est utile à la caractérisation des réseaux de régulation du sommeil, mais que l évaluation fonctionnelle in vivo demeure indispensable. Ainsi, au niveau du tronc cérébral, l influence sérotoninergique médiée par les R5-HT1A pourrait impliquer le noyau GABAergique du DTg, comme nous l avons montré, mais aussi possiblement de nombreux autres noyaux méso-pontiques de nature glutamatergique et sérotoninergique. Ces résultats ont permis d établir un schéma hypothétique des influences médiées par les R5-HT1A dans les circuits neuronaux du tronc cérébral impliqués dans la genèse du SP et de ses caractéristiques toniques et phasiquesPARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Hypocretins in the control of sleep and wakefulness.

During the past 10 years since the discovery of hypocretins (Hcrt, also called orexins), the list of their physiologic implications has been growing, from their primary roles in the sleep-wake cycle and feeding to the control of the cardiovascular system, pain, locomotion, stress, and addiction as well as their involvement in psychiatric disorders such as panic, anxiety, and depression. This diverse set of functions is consistent with the localization of Hcrt neurons in the lateral hypothalamus, a major integrating center of sensory inputs and emotional processes, and their widespread excitatory projections throughout the brain. Newly developed optical tools allow us to manipulate the activity of genetically identified neurons with millisecond precision in vivo and to test specific hypotheses about the causal relationships between Hcrt cells and specific behaviors. Here, we review the basic roles of the Hcrt peptides and discuss how these new technologies increase our understanding of the underpinnings of alertness and arousal.info:eu-repo/semantics/publishe

Wolbachia segregation dynamics and levels of cytoplasmic incompatibility in Drosophila sechellia.

In Drosophila sechellia, the endocellular bacterium Wolbachia induces cytoplasmic incompatibility (CI): in crosses involving infected males, a partial or complete embryonic mortality occurs unless the female bears the same Wolbachia. D. sechellia is known to harbour two Wolbachia variants, namely wSh and wSn, closely related to wHa and wNo, respectively, two strains infecting the populations of D. simulans from the Seychelles archipelago and New Caledonia. Strikingly, the two species show similar infection patterns: in D. sechellia, wSh can be present on its own or in double infection with wSn, but individuals carrying wSn only do not occur; in D. simulans, wHa can be present on its own or in double infection with wNo, but individuals carrying wNo only do not occur, or occur at very low frequency. Previous experiments on D. simulans showed that lines singly infected by wNo can be obtained by segregation, and stably maintained. Here we investigate this issue in D. sechellia through an 18 generation experiment, and show that wSn and wSh singly infected lines can arise by segregation. Using singly infected lines obtained in this experiment, we estimate the CI intensities of wSh and wSn in D. sechellia, and compare these to the CI intensities of the same Wolbachia injected into D. simulans. Our results do not suggest any consistent effect of the host species on the CI induced by wSh. On the contrary, it seems that wSn expression is repressed by host factors in D. sechellia.info:eu-repo/semantics/publishe

Serotonin and Sleep

info:eu-repo/semantics/publishe

It takes two to tango: Dorsal direct and indirect pathways orchestration of motor learning and behavioral flexibility.

The striatum as the main entry nucleus of the basal ganglia is long known to be critical for motor control. It integrates information from multiple cortical areas, thalamic and midbrain nuclei to refine and control motion. By tackling this incredible variety of input signals, increasing evidences showed a pivotal role, particularly of the dorsal striatum, in executive functions. The complexity of the dorsal striatum (DS) in its compartmentalization and in the nature and origin of its afferent connections, makes it a critical hub controlling dynamics of motor learning and behavioral or cognitive flexibility. The present review summarizes findings from recent studies that utilize optogenetics with complementary technologies including electrophysiology, activity imaging and tracing methods in rodents to elucidate the functioning and role of discrete regions and specific pathways of the DS in behavioral flexibility, with an emphasis on the processes leading to initial action sequence or serial order learning and reversal learning.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Heterogeneous distribution of the serotonin 5-HT(1A) receptor mRNA in chemically identified neurons of the mouse rostral brainstem: Implications for the role of serotonin in the regulation of wakefulness and REM sleep.

The 5-HT(1A) receptor (5-HT(1A)R) plays a key role in the inhibitory influence of serotonin (5-HT) on rapid eye movement (REM) sleep in rodents. However, the neuronal networks mediating such influence are mostly unknown, notably in the mouse. This led us to map 5-HT(1A)R mRNA, by in situ hybridization histochemistry (ISHH), and to characterize the neuronal phenotype of 5-HT(1A)R mRNA-positive neurons by dual ISHH and ISHH combined with immunohistochemistry, throughout the mouse rostral brainstem, a pivotal region for the generation of REM sleep and cortical activation. 5-HT(1A)R mRNA was found in most 5-HT neurons in the dorsal raphe (DR), the median raphe (MnR), the B9, and the interpeduncular (IP) nuclei. 5-HT(1A)R mRNA-positive neurons were also identified in individualized clusters of gamma-aminobutyric acid (GABA)ergic neurons in the DR and in neurons of an undetermined phenotype in the MnR. In addition, 1) GABAergic neurons of the ventral portion of Gudden's dorsal tegmental nucleus (DTg), the IP, and the caudal portion of the deep mesencephalic nucleus (DpMe), and 2) glutamatergic neurons scattered in the caudal pontine reticular nucleus (PnC) and densely packed in the internal lateral parabrachial subnucleus (PBil) also expressed 5-HT(1A)R mRNA. In contrast, no specific 5-HT(1A)R-related ISHH signal was generally detected in brainstem cholinergic and catecholaminergic neurons. These results emphasize the role of 5-HT(1A)R as an autoreceptor and the phenotypical heterogeneity of 5-HT(1A)R-expressing neurons within the DR and the MnR in the mouse brain. They also provide a neuroanatomical basis for understanding the influence of 5-HT(1A)R on REM sleep and wakefulness.info:eu-repo/semantics/publishe

Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses

The hypothalamic-pituitary-adrenal (HPA) axis functions to coordinate behavioural and physiological responses to stress in a manner that depends on the behavioural state of the organism. However, the mechanisms through which arousal and metabolic states influence the HPA axis are poorly understood. Here using optogenetic approaches in mice, we show that neurons that produce hypocretin (Hcrt)/orexin in the lateral hypothalamic area (LHA) regulate corticosterone release and a variety of behaviours and physiological hallmarks of the stress response. Interestingly, we found that Hcrt neuronal activity and Hcrt-mediated stress responses were inhibited by the satiety hormone leptin, which acts, in part, through a network of leptin-sensitive neurons in the LHA. These data demonstrate how peripheral metabolic signals interact with hypothalamic neurons to coordinate stress and arousal and suggest one mechanism through which hyperarousal or altered metabolic states may be linked with abnormal stress responses.SCOPUS: ar.jinfo:eu-repo/semantics/publishe