| Matilde Cordero-Erausquin, PhD |
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Research Interests
Nociceptive (pain-related) stimuli enter the central nervous system at the dorsal horn of the spinal cord, where the information is integrated before being relayed to the brain. However, the network on which this integration relies is still poorly understood; the aim of our research is to elucidate its synaptic organisation.
We focus on a population of interneurones that release acetylcholine, a well documented modulator of sensory transmission at the spinal level. Our project aims at identifying the cellular basis of this modulation, by characterising cholinergic interneurones, and in particular their position and role within the DH network of sensory neurones.
Cholinergic neurones are rare, dispersed in the dorsal horn and have no recognisable morphological characteristic. To overcome this difficulty, we obtained, from the lab of Hannah Monyer (Heidelberg University), transgenic mice expressing the green fluorescent protein (GFP) specifically in cholinergic neurons (see figure).
At the moment, we combine electrophysiological patch-clamp recordings (on adult mice spinal slices and in culture) and detailed morphological and immunocytochemical analysis. We also master and plan to perform single-cell RT-PCR, calcium imaging, and injections of transynaptic viral vectors.
With this comprehensive approach, our objectives are to :
(1) determine the types and properties of cholinergic interneurones
(2) identify the neurones innervating these cholinergic neurones
(3) identify the spinal targets of cholinergic neurones
(4) analyse the properties of cholinergic transmission in the dorsal horn
(5) identify the way cholinergic neurones control the sensory inputs to the spinal cord
Beyond enhancing our comprehension of cholinergic modulation of sensory transmission, our project addresses some aspects of neurotransmitter co-release (cholinergic dorsal horn neurones contain GABA). It also participates to the elucidation of the microcircuitry of the sensory dorsal horn, and of the mode of action of classical analgesics (morphine, clonidine) that are known to involve the spinal cholinergic system.
Publications
(top) Differential maturation of GABA action and anion reversal potential in spinal lamina I neurons: impact of chloride extrusion capacity.
Cordero-Erausquin M., Coull J.A.M., Boudreau D., Rolland M. and De Koninck Y.
J. of Neuroscience (2005) 25: 9613-9623
Nicotine differentially activates inhibitory interneurons and projection neurons in the spinal cord. Cordero-Erausquin M., Pons S., Faure Ph. and Changeux J.P.
Pain (2004) 109: 308-308
Function and subunit composition of nicotinic receptors in dopaminergic neurons investigated with knockout mice. Champtiaux N., Gotti C., Cordero-Erausquin M., David D.J., Przybylski C., Léna C., Le Novère N., Arroyo-Jimenez M.D., Clementi F., Moretti M., Rossi F.M., McIntosh J.M., Gardier A.M., and Changeux J.P.
J. of Neuroscience (2003) 23: 7820-7829
Tonic nicotinic modulation of serotoninergic transmission in the spinal cord .
Cordero-Erausquin, M. & Changeux, J.P., PNAS 98 (5) : 2803-2807
Nicotinic function: new perspectives from knockout mice .
Cordero-Erausquin, M., Marubio, L.M., Klink, R., Changeux, J.P., TIPS (2000) 21 : 211-217
Reduced antinociception in mice lacking neuronal nicotinic receptor subunits.
Marubio, L.M., Arroyo-Jimenez, M.M., Cordero-Erausquin, M., Léna, C., Le Novère, N., Huchet, M., Damaj, M.I., Changeux, J.P. Nature (1999) 398 : 805-810
Diversity and distribution of nicotinic acetylcholine receptors in the locus ceruleus neurons.
Léna, C., d'Exaerde, A.D., Cordero-Erausquin, M., Le Novere, N., Arroyo-Jimenez, MD, Changeux, JP, PNAS (1999) 96 (21) : 12126-12131
Funding
(top) The department “Nociception et Douleur” benefits from a rolling (annual) funding from the CNRS and the Ministry of Graduate Education and Research. Additional fundings:
April 2008: Scientific Council of Strasbourg University, “Characterisation of cholinergic neurones in the dorsal horn of the spinal cord, and their role in nociceptive transmission” (Principal applicant: Matilde Cordero-Erausquin).
January 2008: Scientific Council of the INCI, “Characterisation of cholinergic neurones in the dorsal horn of the spinal cord, and their role in nociceptive transmission” (Principal applicant: Matilde Cordero-Erausquin).
2007-2009: National Research Agency (ANR-07-NEURO-012-01), “Anatomical and functional characterization of the spinal neuronal networks underlying development of hyperalgesia and allodynia during acute and chronic pain” (Principal applicant: Rémy Schlichter).
2007-2008: Institut Upsa de la Douleur, "Etude neuroanatomique et fonctionnelle des réseaux neuronaux impliqués dans le développement des états hyperalgésiques et allodyniques associés aux douleurs inflammatoires" (Principal applicant: Rémy Schlichter).