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Topic Name: “Double personality” of the inhibiting neurons
Category: Biodesign
Research persons: Celine Jean-Xavier, George Z. Lied, Michael J.O' Donovan, Daniel Cattaert, and Laurent Vinay
Location: PNAS,500 Fifth Street NW, NAS 335,Washington, DC 20001, United States
Details
An inhibiting neuron acts as such when the chloride concentration is weak in the target cells. And if this concentration is modified, is the effectiveness of neuronal inhibition affected? The team of Laurent Vinay, director of the Unit “Plasticity and physiopathology of motricity” (P3M, CNRS/University of the Mediterranean - Aix-Marseilles 2) has just revealed the double personality of inhibition: this one can become excitation in the event of light increase in the chloride concentration. This discovery calls into question the use of certain therapeutic strategies implemented in certain pathologies (epilepsy, lesions of spinal cord or pains chronic). Carried out in collaboration with the Center of intégratives and cognitive neurosciences (CNRS/Universities Bordeaux 1 and 2) and an American laboratory of the “National Institute of Neurological Disorders and Stroke” (1), this work is the publication on June 27 object in review PNAS.
To transmit relevant and coherent messages through the networks of neurons of the spinal cord and brain, a balance between the activities of the exiting neurons and those of the inhibiting neurons are of primary importance. As example, the locomotion is generated by networks of neurons located in the former part of the lumbar spinal cord, called CPGs for “Exchange pattern generators for locomotion”. In same time, the inhibiting neurons intervene in alternations left right-hand side/and the movements of inflection/extension, two phenomena characteristic of the locomotion.
To transmit relevant and coherent messages through the networks of neurons of the spinal cord and brain, a balance between the activities of the exiting neurons and those of the inhibiting neurons are of primary importance. As example, the locomotion is generated by networks of neurons located in the former part of the lumbar spinal cord, called CPGs for “Exchange pattern generators for locomotion”. In same time, the inhibiting neurons intervene in alternations left right-hand side/and the movements of inflection/extension, two phenomena characteristic of the locomotion. Many pathologies of the central nervous system like the spasticity (muscular stiffness), which is frequently observed among patients hemiplegic or paraplegic, are correlated with a dysfunction of the inhibiting neurons. Let us point out that the neurons release from the neuro-transmitters (2), which activate receivers located at the surface of other neurons (or target cells). Their action is inhibiting when the concentration in ions chloride in the target cells is weak. This phenomenon is controlled by proteins of the membrane of neurons, called KCC2 (3). Implied in the migration of ion chloride, these proteins appear “faded” in various pathologies the such the chronic epilepsy or pains.
But, in the event of modification of the concentration in ions chloride, that does it occur on the level from the effectiveness from neuronal inhibition? By looking further into this question via an approach pluridisiciplinaire (4), the team directed by Laurent Vinay (P3M, CNRS/Université Aix-Marseilles 2, Marseilles), in collaboration with a team of the Center of intégratives and cognitive neurosciences of Bordeaux and American researchers of the laboratory of neuronal control of the “National Institute of Neurological Disorders and Stroke” in Bethesda (Maryland), showed that a light increase in this concentration can reverse the “inhibiting” effect and cause an amplification of the excitations received by the neuron, thus starting a neuronal dysfunction. This work highlights the “double personality” of the inhibition which is thus a function of the concentration of the ions chloride and especially, of the localization of the inhibiting and exiting entries at the surface of the neuron. Another result of premium importance: the regulation of the concentration of the neurons in ions chloride is a vital function. What results in calling into question the effectiveness of the therapeutic strategies aiming at increasing the inhibition of the neurons using substances mimant the effect of the inhibiting neuro-transmitters. The benefit of these therapies can be effective only in the presence of one concentration in ions weak chloride in the cells. In the contrary case, their action could be noxious. This study implies the development of a new therapeutic way, targeted on the systems of regulation of chloride.
Notes :
(1) The “national Institute of Neurological Disorders and Stroke” (national Institute of the neurological disorders and vascular accidents) belongs to the “National Institute of Health” or national Institute of health American.
2) The neuro-transmitters are chemical substances allowing the communication between neurons.
(3) KCC2 is responsible for the pumping of the ions chloride towards the outside of the nervous cells.
(4) This approach utilized neurophysiology, immunohistochimy, modeling and simulations
References :
Dual personality of GABA/glycine-mediated depolarizations in immature spinal cord. Celine Jean-Xavier, George Z. Lied, Michael J.O' Donovan, Daniel Cattaert, and Laurent Vinay. PNAS, June 27, 2007
Contacts :
Chercheur
Laurent Vinay,
T 04 91 16 40 86
vinay@dpm.cnrs-mrs.fr
In The Images-
Illustration of the “double personality” of the inhibiting synaptic transmission on the level spinal © Laurent Vinay/CNRS 2007 (this visual is available near the photographic library of CNRS - phototheque@cnrs-bellevue.fr).
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