The preparation of oblique spinal cord slices for ventral root stimulation

Video Link: The video component of this article can be found at: https://www.jove.com/video/54525Electrophysiological recordings from spinal cord slices have proven to be a valuable technique to investigate a wide range of questions, from cellular to network properties. We show how to prepare viable oblique slices of the spinal cord of young mice (P2 - P11). In this preparation, the motoneurons retain their axons coming out from the ventral roots of the spinal cord. Stimulation of these axons elicits back-propagating action potentials invading the motoneuron somas and exciting the motoneuron collaterals within the spinal cord. Recording of antidromic action potentials is an immediate, definitive and elegant way to characterize motoneuron identity, which surpasses other identification methods. Furthermore, stimulating the motoneuron collaterals is a simple and reliable way to excite the collateral targets of the motoneurons within the spinal cord, such as other motoneurons or Renshaw cells. In this protocol, we present antidromic recordings from the motoneuron somas as well as Renshaw cell excitation, resulting from ventral root stimulation.Financial supports were provided by the Agence Nationale pour la Recherche (HYPER-MND, ANR-2010-BLAN-1429-01), the NIH-NINDS (R01NS077863), the Thierry Latran Foundation (OHEX Project), the French association for myopathy (grant number 16026) and Target ALS are gratefully acknowledged. Felix Leroy was the recipient of a "Contrat Doctoral" from the Ecole Normale Supérieure, Cachan.Peer reviewe

[Environs d' Agadir-Founti] / levée par le captaine Lamotte d'Incamps

Échelle(s) : [Echelles diverses

[Environs d' Agadir-Founti] / levée par le captaine Lamotte d'Incamps

Échelle(s) : [Echelles diverses

Extending Cable Theory to Heterogeneous Dendrites

Dendrites exhibit many types of electrical and morphological heterogeneities at the scale of a few micrometers. Models of neurons, even detailed models, rarely consider such heterogeneities. Small scale fluctuations in the membrane conductances and the diameter of dendrites are generally disregarded and spines merely incorporated into the dendritic shaft. Using the two scales method known as homogenization, we establish explicit expressions for the small scale fluctuations of the membrane voltage, and we derive the cable equation satisfied by the voltage, when these fluctuations are averaged out. We establish rigorously under which conditions an heterogeneous dendrite can be approximated by an homogeneous cable. We consider different distributions of synapses, orderly or random, on a passive dendrite, and we investigate when replacing excitatory and inhibitory synaptic conductances by their local averages leads to a small error in the voltage. This indicates in which regimes the approximations made in compartmental models are justified. We extend these results to active membranes endowed with voltagedependent conductances or NMDA receptors. Then, we show that a spiny dendrite behaves as a smooth dendrite when the conductance of the spine neck is large compared to the conductance of the synapses impinging on the spine head, but also in the opposite situation, when it is small compared to the synaptic conductance. In this last regime, the only effect of spines is to deliver an effective synaptic current to the dendrite. This suggests that pedunculated and stubby spines might play complementary roles in synaptic integration. Finally, we analyze how varicosities affect voltage diffusion in dendrites and discuss their impact on the spatiotemporal integration of synaptic input

Potassium currents dynamically set the recruitment and firing properties of F-type motoneurons in neonatal mice

In neonatal mice, fast- and slow-type motoneurons display different patterns of discharge. In response to a long liminal current pulse, the discharge is delayed up to several seconds in fast-type motoneurons and their firing frequency accelerates. In contrast, slow-type motoneurons discharge immediately, and their firing frequency decreases at the beginning of the pulse. Here, we identify the ionic currents that underlie the delayed firing of fast-type motoneurons. We find that the firing delay is caused by a combination of an A-like potassium current that transiently suppresses firing on a short time scale and a slowly-inactivating potassium current that inhibits the discharge over a much longer time scale. We then show how these intrinsic currents dynamically shape the discharge threshold and the frequency-input function of fast-type motoneurons. These currents contribute to the orderly recruitment of motoneurons in neonates and might play a role in the postnatal maturation of motor units.Financial support was provided by the Agence Nationale pour la Recherche(HYPER-MND, ANR-2010-BLAN-1429-01), the National Institute of Neuro-logical Disorders and Stroke (R01-NS-077863), the Thierry Latran Fundation(OHEX Project), and Target ALS are gratefully acknowledged. F. Leroy wasthe recipient of a “Contrat Doctoral” from the Ecole Normale Supérieure,Cachan.Peer reviewe

Sensibilisation au syndrome psychotraumatique chez les demandeurs d 'asile (intérêt de la prise en charge et caractéristiques de cette entité à travers onze entretiens)

Les médecins généralistes dans leur cabinet, les médecins urgentistes, ou encore les médecins des différentes structures de soins dédiées aux plus démunis peuvent être amenés à prendre en charge des demandeurs d'asile (DA). Ces patients souffrent souvent de troubles psycho-traumatiques. Ce travail sensibilise à ces troubles et à leurs caractéristiques au sein de cette population ainsi que sur les bénéfices ressentis à la suite de soins adaptés, en termes de qualité de vie et d'intégration sociale. Il s'agit d'une étude qualitative, réalisée au cours de onze entretiens à travers lesquels nous retrouvons les différentes spécificités de ce syndrome chez les DA. Les patients décrivent un ensemble de symptômes qu'il faut savoir reconnaître pour dépister les troubles afin de les prendre en charge de façon appropriée. Par ailleurs, ces entretiens soulignent l'intérêt de ces soins, puisque l'on constate que les patients éprouvent, d'une part, une amélioration de leur quotidien et que, d'autre part le suivi permet une meilleure intégration grâce à l'évolution positive de nombreux symptômes handicapant dans ce domaine. De nombreux facteurs freinateurs interviennent dans cette démarche de soins. Il faut en effet considérer la dimension transculturelle inhérente à cette prise en charge, ainsi que le contexte social des patients. Ce travail illustre les principaux facteurs et permet d'ouvrir une discussion sur les tenants et les aboutissants de ce suivi particulier. Il permet également d'aborder certaines particularités de l'éthnopsychiatrie. La sensibilisation du corps médical aux troubles psycho-traumatiques permet de mettre en place les soins appropriés, bénéfiques aux patients.General practitioners in their offices, emergency physicians or those working in various structures dedicated to homeless can eventually take care of asylum migrants. These patients often suffer from psycho-traumatic disorders. This work emphasizes these troubles and their characteristics in this specific population, as well as the benefits of adapted cares on their quality of life and social integration. This qualitative study was conducted through eleven asylum migrant s interviews during which we have found various specificities of psycho-traumatic disorders. Those patients describe a set of symptoms that need to be identified before naming the troubles and be able to cure them in the most appropriate way. In addition, these interviews highlight the benefit of the cares as patients mention improvements in their daily life. It also appears that a better social integration can be noticed through the positive evolution of numerous symptoms disabling in that field. Numerous slowing factors impact the care process. One has indeed to considerate the transcultural dimension of this handover as well as the social environment of the patients. This work illustrates the main factors and opens the debate on the ins and outs of this particular care. It also allows an approach to certain ethno psychiatry peculiarities. Improving awareness regarding psycho-traumatic disorders allows setting appropriate cares, proven to be beneficial to asylum migrant patients.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Early electrophysiological abnormalities in lumbar motoneurons in a transgenic mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a lethal, adult-onset disease characterized by progressive degeneration of motoneurons. Recent data have suggested that the disease could be linked to abnormal development of the motor nervous system. Therefore, we investigated the electrical properties of lumbar motoneurons in an in-vitro neonatal spinal cord preparation isolated from SOD1(G85R) mice, which is a transgenic model of amyotrophic lateral sclerosis. The study was performed on young animals at the beginning of their second week, between postnatal days 6 and 10. Measurements of resting membrane potential and action potential characteristics of motoneurons were similar in wild-type and SOD1(G85R) mice. However, the input resistance of motoneurons from transgenic mice was significantly lower than that of wild-type animals, whereas their membrane capacitance was increased, strongly suggesting larger SOD1(G85R) motoneurons. Furthermore, the slope of the frequency-intensity curve was steeper in motoneurons from wild-type pups. Interestingly, the input resistance as well as the slope of the frequency-intensity curves of other spinal neurons did not show such differences. Finally, the amplitude of dorsal root-evoked potentials following high-intensity stimulation was significantly smaller in SOD1(G85R) motoneurons. The superoxide dismutase 1 mutation thus induces specific alterations of the functional properties of motoneurons early in development

Flexible processing of sensory information induced by axo-axonic synapses on afferent fibers

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Early abnormalities in transgenic mouse models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative and fatal human disorder characterized by progressive loss of motor neurons. Transgenic mouse models of ALS are very useful to study the initial mechanisms underlying this neurodegenerative disease. We will focus here on the earlier abnormalities observed in superoxide dismutase 1 (SOD1) mutant mice. Several hypotheses have been advanced to explain the selective loss of motor neurons such as apoptosis, neurofilament disorganisation, oxidative stress, mitochondrial dysfunction, astrogliosis and excitotoxicity. Although disease onset appears at adulthood, recent studies have detected abnormalities during embryonic and postnatal maturation in animal models of ALS. We reported that SOD1(G85R) mutant mice exhibit specific delays in acquiring sensory-motor skills during the first week after birth. In addition, physiological measurements on in vitro spinal cord preparations reveal defects in evoking rhythmic activity with N-methyl-DL-aspartate and serotonin at lumbar, but not sacral roots. This is potentially significant, as functions involving sacral roots are spared at late stages of the disease. Moreover, electrical properties of SOD1 lumbar motoneurons are altered as early as the second postnatal week when mice begin to walk. Alterations concern the input resistance and the gain of SOD1 motoneurons which are lower than in control motoneurons. Whether or not the early changes in discharge firing are responsible for the uncoupling between motor axon terminals and muscles is still an open question. A link between these early electrical abnormalities and the late degeneration of motoneurons is proposed in this short review. Our data suggest that ALS, as other neurodegenerative diseases, could be a consequence of an abnormal development of neurons and network properties. We hypothesize that the SOD1 mutation could induce early changes during the period of maturation of motor systems and that compensatory mechanisms-linked to developmental spinal plasticity-might explain the late onset of the disease