DEVELOPMENTAL ALTERATIONS IN NMDA RECEPTOR-MEDIATED [CA2+](I) ELEVATION IN SUBSTANTIA-GELATINOSA NEURONS OF NEONATAL RAT SPINAL-CORD

Using spinal cord slices prepared from neonatal rats, the intracellular free Ca2+ concentration ([Ca2+](i)) in neurons located in the dorsal horn substantia gelatinosa (SG) was measured with microscopic fluorometry by loading fura 2-AM into neurons. Developmental alterations in the elevation of [Ca2+](i) elicited by the glutamate analogs, NMDA and AMPA, were investigated from postnatal day (PNDs) 1 to 17. During the Ist week of postnatal life, when neuronal maturation of the SG is known to take place, the NMDA response remained large or even slightly increased. It subsequently showed a gradual decline. This pattern of postnatal changes is consistent with previously reported autoradiographic studies on NMDA-binding sites. The affinity of receptors for NMDA was found to decrease constantly during the period examined. The AMPA response and resting [Ca2+](i) showed no significant developmental changes. Neonatal treatment with capsaicin, which has been shown to degenerate fine primary afferent fibers terminating in the SG, delayed the developmental decline in the NMDA-induced [Ca2+](i) response. It is suggested that the number and the molecular properties of NMDA receptors expressed in the SG change during early postnatal neuronal maturation. The temporal coincidence between postnatal alteration in NMDA-induced [Ca2+](i) elevation and neuronal maturation of the SG may indicate that intracellular Ca2+ regulated by NMDA receptor activation is related to postnatal neuronal maturation. Activation of fine primary afferent fibers may contribute to the observed developmental alterations in the NMDA response of SG neurons.