OXYTOCIN MODULATES GLUTAMATERGIC SYNAPTIC TRANSMISSION BETWEEN CULTURED NEONATAL SPINAL-CORD DORSAL HORN NEURONS

The functional characteristics of binding sites for the neuropeptide o xytocin (OT) detected by radioautography in laminae I and II of the do rsal horn (DH) and on cultured neonatal DH neurons were studied on the latter using perforated patch-clamp recordings, The neurons were iden tified by their spike discharge properties and on the basis of the pre sence of met-enkephalin-like and glutamate decarboxylase-like immunore activities. OT (100 nM) never induced any membrane current at a holdin g potential of -60 mV but increased the frequency of spontaneously occ urring AMPA receptor-mediated EPSCs or the mean amplitude of electrica lly evoked EPSCs in a subset (35%) of neurons, The frequency of miniat ure EPSCs (m-EPSCs) recorded in the presence of 0.5 mu M tetrodotoxin was also increased by OT (100 nM) without any change in their mean amp litude, indicating an action at a site close to the presynaptic termin al, The decay kinetics of any type of EPSC were never modified by OT. The effect of OT was reproduced by [Thr(4),Gly(7)]-OT (100 nM), a sele ctive OT receptor agonist, and blocked by d(CH2)(5)-[Tyr(Me)(2),Thr(4) ,Tyr-NH29]-ornithine vasotocin (100 nM), a specific OT receptor antago nist, Reducing the extracellular Ca2+ concentration from 2.5 to 0.3 mM in the presence of Cd2+ (100 mu M) reversibly blocked the effect of O T on m-EPSCs, The OT receptors described here may represent the substr ate for modulatory actions of descending hypothalamo-spinal OT-contain ing pathways on the nociceptive system.