Synaptic activation of N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors in the mossy fibre pathway in adult and immature rat cerebellar slices.

The participation of excitatory amino acid receptors in mossy fibre-granule cell synapses in lobule VIa of adult and immature rat cerebellar slices was investigated using an extracellular grease-gap technique. For the immature slices, the age selected (14 days after birth) was one at which the sensitivity of granule cells to exogenous N-methyl-D-aspartate is much higher than in the adult. The principal synaptic potentials observed after low-frequency electrical stimulation of the white matter resembled closely those found to be centred in the granule cell layer in field potential studies in the cat in vivo. They comprised a short latency negative potential, a slow negative wave and, in the adult, a further late negative wave. In the adult, with 1.2 mM Mg2+ in the perfusing solution, none of these potentials was significantly affected by the N-methyl-D-aspartate antagonist, 2-amino-5-phosphonovalerate, but they were all markedly inhibited by the broad spectrum antagonist, kynurenate, and, more potently, by the selective non-N-methyl-D-aspartate receptor blocker, 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline. After removal of Mg2+, which has a blocking action on the ion channels associated with N-methyl-D-aspartate receptors, the size of all the potentials increased. The increase in the short latency potential was insensitive to 2-amino-5-phosphonovalerate but a component of the slow negative wave (and of the late negative wave) was reduced back to control levels by the antagonist. Application of 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (10 microM) in Mg2+-free solution revealed, in near isolation, a slow wave (latency to peak, 28 ms) which could be abolished by 2-amino-5-phosphonovalerate. In the immature slices, bathed in normal (Mg2+-containing) medium, 2-amino-5-phosphonovalerate caused a small reduction in the short latency potential and inhibited a component of the slow negative wave which could, again, be observed in relative isolation after perfusion of 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline. Removal of Mg2+ increased the amplitudes of the short latency potential and the slow negative wave in a manner which was sensitive to 2-amino-5-phosphonovalerate and increased the size of the slow, 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline-resistant wave. It is concluded that glutamate is likely to be the transmitter released by mossy fibres, at least those innervating lobule VIa.(ABSTRACT TRUNCATED AT 400 WORDS)