Histamine modulates spinal motoneurons and locomotor circuits

Spinal motoneurons and locomotor networks are regulated by monoamines, among which, the contribution of histamine has yet to be fully addressed. The present study investigates histaminergic regulation of spinal activity, combining intra- and extracellular electrophysiological recordings from neonatal rat spinal cord in vitro preparations. Histamine dose-dependently and reversibly generated motoneuron depolarization and action potential firing. Histamine (20μM) halved the area of dorsal root reflexes and always depolarized motoneurons. The majority of cells showed a transitory repolarization, while 37% showed a sustained depolarization maintained with intense firing. Extracellularly, histamine depolarized ventral roots (VRs), regardless of blockage of ionotropic glutamate receptors. Initial, transient glutamate-mediated bursting was synchronous among VRs, with some bouts of locomotor activity in a subgroup of preparations. After washout, the amplitude of spontaneous tonic discharges increased. No desensitization or tachyphylaxis appeared after long perfusion or serial applications of histamine. On the other hand, histamine induced single motoneuron and VR depolarization, even in the presence of tetrodotoxin (TTX). During chemically induced fictive locomotion (FL), histamine depolarized VRs. Histamine dose-dependently increased rhythm periodicity and reduced cycle amplitude until near suppression. This study demonstrates that histamine induces direct motoneuron membrane depolarization and modulation of locomotor output, indicating new potential targets for locomotor neurorehabilitation

V1 interneurons regulate the pattern and frequency of locomotor-like activity in the neonatal mouse spinal cord.

In the mouse spinal cord, V1 interneurons are a heterogeneous population of inhibitory spinal interneurons that have been implicated in regulating the frequency of the locomotor rhythm and in organizing flexor and extensor alternation. By introducing archaerhodopsin into engrailed-1-positive neurons, we demonstrate that the function of V1 neurons in locomotor-like activity is more complex than previously thought. In the whole cord, V1 hyperpolarization increased the rhythmic synaptic drive to flexor and extensor motoneurons, increased the spiking in each cycle, and slowed the locomotor-like rhythm. In the hemicord, V1 hyperpolarization accelerated the rhythm after an initial period of tonic activity, implying that a subset of V1 neurons are active in the hemicord, which was confirmed by calcium imaging. Hyperpolarizing V1 neurons resulted in an equalization of the duty cycle in flexor and extensors from an asymmetrical pattern in control recordings in which the extensor bursts were longer than the flexor bursts. Our results suggest that V1 interneurons are composed of several subsets with different functional roles. Furthermore, during V1 hyperpolarization, the default state of the locomotor central pattern generator (CPG) is symmetrical, with antagonist motoneurons each firing with an approximately 50% duty cycle. We hypothesize that one function of the V1 population is to set the burst durations of muscles to be appropriate to their biomechanical function and to adapt to the environmental demands, such as changes in locomotor speed

Rôle du tronc chez les mammifères au cours de la locomotion (approche électrophysiologique et cinématique)

La locomotion résulte de phénomènes posturaux complexes qui nécessitent le fonctionnement intégré des membres antérieurs, postérieurs et du tronc. Le maintiens d un équilibre dynamique durant la propulsion vers l avant ne peut être réalisé que parce qu il existe des processus internes de coordination entrez les réseaux nerveux qui commandent la contraction rythmique de ces différents niveaux. Alors que la grande majorité des études sur la locomotion porte sur le fonctionnement des membres postérieurs, notre intérêt s est focalisé sur le rôle du tronc et l organisation des réseaux neuronaux spinaux sous-tendant son activité en coordination avec les membres. Trois approches différentes ont été réalisées : (1) cinématique permettant de visualiser dans l espace les mouvements du rat de sa naissance à l âge du sevrage ; (2) électrophysiologique sur préparation de moelle épinière isolée in vitro centrée sur les réseaux spinaux responsables de l activité motrice chez le rat nouveau-né ; (3) électromyographique pour déterminer le patron d activation des muscles axiaux chez l homme. Nos résultats montrent qu au cours du déplacement, le tronc se courbe rythmiquement chez le rat et l homme. Chez le rat, le développement modifie la sortie motrice en amplitude et en vitesse d exécution principalement. La courbe du tronc serait due à la propagation séquentielle de l onde motrice le long de la moelle épinière. Nos données suggèrent également que les réseaux responsables de la propagation métachronale des patrons moteurs au cours de la locomotion correspondent à ceux observés chez les invertébrés ou vertébrés inférieurs et seraient donc conservés à travers l évolution.Locomotion involves complex synergistic postural regulation requiring the integrated functioning of all the body musculature, including hind- and forelimb, trunk and neck muscles. Dynamic equilibrium during forward locomotion is preserved by internal process of coordination between neuronal that drive rhythmic contraction of this muscles. Although numerous studies have focused on understanding how the CNS controls hindlimb movements, very few studies has been devotes to understanding the functioning of neural networks that activate trunk muscles in coordination with limb movements. To answer approach these question three main approaches have been used. (1) a kinematic approach allowing to visualize from birth to weaning day, the rat movements in a 3-D environment ; (2) an electrophysiological approach on an in vitro isolated spinal cord preparation based on spinal neuronal networks responsible for motor activity in the newborn rat ; (3) an electromyographic approach to determine the pattern of activity of axial movements in human. Our results show that there is a rhythmic sequential change in trunk curvature during the step cycle. In rats, development modifies the amplitude an velocity of the motor output. The trunk bending could be related to the sequential propagation of the motor wave along the spinal cord. Our data suggest that the networks responsible for metachronal propagation of motor patterns during locomotion may correspond to those observed in vertebrates or lower vertebrates, and thus are highly conserved.BORDEAUX2-BU Sci.Homme/Odontol. (330632102) / SudocSudocFranceF

Montcalm devant la postérité : étude historique /

Mode of access: Internet

De l'enseignement du droit chez les Romains (avant Justinien) : discours prononcé à la séance solennelle de rentrée de la conférence de Portalis, le 3 décembre 1883 / par Edmond Falgairolle

Appartient à l’ensemble documentaire : PACA1Avec mode text

The effects of drugs used to initiate locomotor-like activity on Fluoro-Gold labeling in the presence of TTX.

<p>(A1–C1) Probability maps for Fluoro-Gold labeling in response to TTX and Dopamine (A1), TTX and Serotonin (5-HT). (B1) TTX, Dopamine, and 5-HT (C1). The color map to the right of A1, B1, and C1 shows the probability of labeling. (A2–C2) Difference maps compared to TTX for Fluoro-Gold labeling in response to TTX and Dopamine (A2), TTX and 5-HT (B2) and TTX and dopamine + 5-HT (C2). The colormap to the right of A2, B2, and C2 shows the color coding for pixels that differed statistically (p<0.05) from control.</p

L-glutamic acid as well as TBOA induced uptake of Fluoro-Gold.

<p>(A1) Application of 5mM L-glutamic acid resulted in widespread labeling but not as extensive as that obtained with AMPA or Kainate administration. (A2) Probability map for L-glutamate-induced uptake. (B) Application of TBOA (50 μM) also led to neuronal uptake. (B2) Probability map for TBOA. The drug was applied for 10 minutes and a further 30 min in the presence of Fluoro-Gold. The color map to the right of A2 and B2 shows the probability of labeling.</p

Fluoro-Gold uptake is abolished in control conditions, and is decreased when AMPA is applied in the presence of blockers of endocytosis.

<p>(A) Image of a hemicord when a hypertonic ACSF (450 mM sucrose) replaced the control ACSF. Neuronal labeling was almost abolished. (B1) Image of a hemicord when AMPA was applied together with hypertonic ACSF (5 μM). (B2) Probability map for AMPA and hypertonic ACSF. (C) Image of a hemicord when Dynasore (1 mM), a dynamin blocker, was applied (D1) When AMPA (5 μM) was co-applied with Dynasore cellular labeling was greatly reduced. (D2) Probability map for co-application of AMPA and Dynasore. The color bar to the right of panel B2 indicates the probability/pixel. (E1 –E2) Show FG uptake under control conditions and during AMPA application in the presence of the scrambled peptide. (F1–F2) Labeling is greatly reduced in the presence of the unscrambled dynamin inhibitory peptide.</p

AMPA receptors were responsible for most of the glutamatergic dye uptake.

<p>(A1) Application of NMDA (20 μM) together with NBQX (20 μM) led to reduced labeling compared to NBQX alone. (A2) Difference map obtained by subtracting the probability map for the NMDA and NBQX from the probability map for NBQX alone. (B1) Application of both AMPA (5 μM) and APV (50 μM) resulted in a labeling pattern similar to that observed with the application of AMPA alone. (B2) Difference map obtained by subtracting the probability map for the AMPA + APV from the probability map for APV alone. (C1) Application of both Kainate (10 μM) and NBQX (20 μM) abolished most of the cellular labeling. (C2) Difference map obtained by subtracting the probability map for the Kainate and GYKI from the probability map for NBQX alone. The colormap to the right of A2, B2, and C2 shows the color coding for pixels that differed statistically (p<0.05) from control.</p