Uptake and release of glycine in the guinea pig cochlear nucleus after axotomy of afferent or centrifugal fibers.

Abstract

Glycine may be an inhibitory transmitter in the mammalian cochlear nucleus (CN). This study attempts to determine if cochlear and/or centrifugal projections to the CN use glycine as a transmitter. The high-affinity uptake and electrically evoked release of exogenous [14C]glycine were measured in vitro in the three major subdivisions of the guinea pig CN: the anteroventral, posteroventral, and dorsal cochlear nuclei (AVCN, PVCN, and DCN, respectively). [14C]Glycine (3.4 microM) was taken up by each subdivision, reaching tissue concentrations six to seven times that in the medium. Subsequent electrical stimulation evoked a Ca2+-dependent release of [14C]glycine from each subdivision. These activities were compared in subdivisions fr0m unlesioned animals, and from animals with lesions of centrifugal or cochlear projections to the CN. Two knife-cut lesions were made to interrupt centrifugal projections to the CN lying in the right acoustic striae and trapezoid body. In one group of animals, centrifugal fibers projecting mainly to the right AVCN and PVCN were severed, which reduced [14C]glycine uptake and release by 44-53% in these subdivisions, but not in the right DCN. In another group of animals, fibers projecting mainly to the right PVCN and DCN were severed, which reduced [14C]glycine uptake and release by 33-47% in these subdivisions, but not in the right AVCN. In CN subdivisions contralateral to either lesion there was no significant change in [14C]glycine uptake or release. Neither of these lesions altered the uptake or release of D-[3H]aspartate in the right or the left CN. Ablation of the left cochlea, which presumably destroyed cochlear nerve fibers unilaterally, had no effect on [14C]glycine uptake and release. These observations suggest that centrifugal projections contribute a proportion of the glycinergic synaptic endings in the CN. In addition, some glycinergic endings probably arise from neurons intrinsic to the CN. The cochlear nerve contains very few, if any, glycinergic fibers.