Sonic hedgehog signalling in neurons of adult ventrolateral nucleus tractus solitarius.

Olivier Pascual (1, 2) , Elisabeth Traiffort (2, 3) , Darren P. Baker (4) , Alphonse Galdes (4) , Martial Ruat (2, 3) , Jean Champagnat (1, 2)

1 NGI - Neurobiologie génétique et intégrative
2 INAF - Institut de Neurobiologie Alfred Fessard
3 NBCM - Laboratoire de neurobiologie cellulaire et moléculaire
4 Biogen Idec Inc, department of drug Discovery

The transmembrane receptor Patched (Ptc) mediates the action of the diffusing factor Sonic hedgehog (Shh), which is implicated in establishing morphogenetic gradients during embryonic development. Whereas alteration of Ptc function is associated with developmental abnormalities and brain tumors, its functional activity and roles in the adult brain have yet to be elucidated. Here we describe the complementary pattern of Shh and Ptc expression in the rat dorsal vagal motor nucleus and the ventrolateral nucleus tractus solitarius (vNTS), respectively. Those two interconnected structures regulate the cardiorespiratory function during hypoxia. Bath application of a subnanomolar concentration of aminoterminal Shh protein (ShhN) to a slice preparation of the vNTS induces a rapid decrease in neuronal firing followed by a bursting activity that propagates in the neuronal network. Intracellular current injections show that bursts result from an action on the neuronal membrane electro-responsiveness. Both inhibiting and bursting effects are blocked by the monoclonal Shh antibody 5E1 and may require the Ptc binding site of ShhN. Thus, ShhN acting on specific neuronal sites controls electrophysiological properties of differentiated neurons of the vNTS. We speculate on a retrocontrol of cardiorespiratory signals in the vNTS, by Shh generated in dorsal vagal motoneurons.

Mots clés: Alkaline Phosphatase metabolism; Antibodies pharmacology; Cell Proliferation drug effects; Cells Cultured; Cerebellum cytology; Comparative Study; Dose-Response Relationship Drug; Electric Stimulation methods; Embryo; Excitatory Postsynaptic Potentials drug effects; In Situ Hybridization methods; In Vitro; Intracellular Signaling Peptides and Proteins; Lysine analogs & derivatives metabolism; Membrane Proteins; Mice; Neural Inhibition drug effects physiology; Neurons drug effects; physiology radiation effects; Peptide Fragments pharmacology; Rats Sprague-Dawley; Receptors Cell Surface metabolism; Signal Transduction drug effects; Solitary Nucleus cytology; Stem Cells physiology; Trans-Activators

Domaines: Neurosciences [q-bio.NC]

Olivier Pascual, Elisabeth Traiffort, Darren P. Baker, Alphonse Galdes, Martial Ruat, et al.. Sonic hedgehog signalling in neurons of adult ventrolateral nucleus tractus solitarius.. European Journal of Neuroscience, 2005, 22, pp.389. ⟨10.1111/j.1460-9568.2005.04223.x⟩. ⟨hal-00018205⟩