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The Journal of Neuroscience, April 1, 1998, 18(7):2377-2386

Oxytocin Modulates Glutamatergic Synaptic Transmission between Cultured Neonatal Spinal Cord Dorsal Horn Neurons

Young-Hwan Jo, Marie-Elisabeth Stoeckel, Marie-José Freund-Mercier, and Rémy Schlichter

Laboratoire de Neurophysiologie Cellulaire et Intégrée, Unité Mixte de Recherche 7519-Centre National de la Recherche Scientifique, Université Louis Pasteur, 67084 Strasbourg Cedex, France

The functional characteristics of binding sites for the neuropeptide oxytocin (OT) detected by radioautography in laminae I and II of the dorsal horn (DH) and on cultured neonatal DH neurons were studied on the latter using perforated patch-clamp recordings. The neurons were identified by their spike discharge properties and on the basis of the presence of met-enkephalin-like and glutamate decarboxylase-like immunoreactivities. OT (100 nM) never induced any membrane current at a holding potential of 60 mV but increased the frequency of spontaneously occurring AMPA receptor-mediated EPSCs or the mean amplitude of electrically evoked EPSCs in a subset (35%) of neurons. The frequency of miniature EPSCs (m-EPSCs) recorded in the presence of 0.5 µM tetrodotoxin was also increased by OT (100 nM) without any change in their mean amplitude, indicating an action at a site close to the presynaptic terminal. The decay kinetics of any type of EPSC were never modified by OT. The effect of OT was reproduced by [Thr⁴,Gly⁷]-OT (100 nM), a selective OT receptor agonist, and blocked by d(CH₂)₅-[Tyr(Me)²,Thr⁴,Tyr-NH₂⁹]-ornithine vasotocin (100 nM), a specific OT receptor antagonist. Reducing the extracellular Ca²⁺ concentration from 2.5 to 0.3 mM in the presence of Cd²⁺ (100 µM) reversibly blocked the effect of OT on m-EPSCs. The OT receptors described here may represent the substrate for modulatory actions of descending hypothalamo-spinal OT-containing pathways on the nociceptive system.

Key words: EPSCs; oxytocin; AMPA receptors; nociception; Met-enkephalin; GABA; dorsal horn neurons; spinal cord

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Copyright © 1998 Society for Neuroscience  0270-6474/98/1872377-10$05.00/0

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