The present study seeks to identify neurotransmitters mediating binaural inhibition in lateral superior olivary nucleus neurons. Neurons in this auditory structure receive inputs from both ears and are thought to code for localization of sound in space. Iontophoretic application of glycine during monaural stimulation was found to mimic the inhibition observed with binaural stimulation. Binaural inhibition was blocked by application of the glycine receptor antagonist, strychnine, as were the effects of iontophoretic application of glycine. The post-strychnine recovery time course for return of synaptically mediated binaural inhibition and recovery of the effects of iontophoretic glycine application were identical. Although the superior olivary complex (SOC) neurons displaying binaural inhibition could in some cases be inhibited by GABA, the binaural inhibition rarely was blocked by iontophoretic application of the GABA receptor antagonist, bicuculline. These findings suggest that glycine may be a neurotransmitter mediating binaural inhibition in certain SOC neurons and that the projection to the lateral superior olivary nucleus from the medial nucleus of the trapezoid body may be glycinergic.The superior olivary complex (SOC) is the first structure in the ascending auditory pathway to receive bilateral input (for review see Boudreau and Tsuchitani, 1970;Brugge and Geisler, 1978; Tsuchitani, 1978). The auditory nerve on each side projects from the cochlea to the cochlear nucleus on that side. Binaural neurons in the lateral superior olive (LSO) receive their predominant contralateral input from the opposite ventral cochlear nucleus (VCN) via a secure synapse in the ipsilateral medial nucleus of the trapezoid body (MNTB; see Fig. 1). Ipsilateral input comes directly from the homolateral VCN to the same neuron. Ultrastructural studies indicate the existence of at least three types of synaptic endings upon the neurons of the medial superior olive (MSO). The morphological characteristics of these endings suggest that some may be inhibitory but others may be excitatory (Clark, 1969;Perkins, 1973; Schwartz, 1980 trophysiological evidence indicates the existence of neurons in both the MS0 and LSO which are excited by inputs from one ear and inhibited by simultaneous stimulation of the opposite ear (Galambos et al., 1959; Brown, 1968, 1969;Guinan et al., 1972a, b; Tsuchitani, 1977 Tsuchitani, , 1978. The nature of the neurotransmitter mechanisms mediating this inhibition is not known, but the existence of binaural neurons within the SOC provides an opportunity to study the interaction between excitatory and inhibitory synaptic inputs by varying the acoustic stimulus to each ear. Recently, Zarbin et al. (1981), using autoradiographic evidence, demonstrated that strychnine, the specific glycine antagonist, displays significant receptor binding in the rat LSO and minimal binding in the rat MSO.The present study examines binaural inhibition and attempts to antagonize the synaptically mediated binaural inhibition b...

The present study describes substantial, selective, age-related loss of the putative inhibitory neurotransmitter GABA in the central nucleus of the inferior colliculus (CIC) of rat based on immunocytochemical and neurochemical data. For immunocytochemistry, neurons in the CIC were immunolabeled using an antibody against a GABA conjugate in young adult (2- to 7-month-old) and aged (18- to 29-month-old) Fischer-344 rats. Computer-assisted morphometry was then used to generate maps of GABA-immunoreactive neurons in the CIC. The number of GABA-positive neurons was reduced 36% in the ventrolateral portion of the CIC of aged animals (93 neurons/mm2) compared to their matched young adult cohorts (145 neurons/mm2; p less than 0.01). For neurochemistry, basal and K(+)-evoked release of the endogenous amino acids GABA, glutamate (Glu), aspartate (Asp), and tyrosine (Tyr) from micropunches of the CIC were measured in 8 age-paired animals from the 2 age groups using high-performance liquid chromatography. Overflow of radiolabeled acetylcholine (3H-ACh) was also determined. In both age groups, K(+)-evoked release of GABA, Glu, Asp, and 3H-ACh from CIC punches was significantly enhanced above basal efflux (+200, +215, +163, and +309%, respectively), while Tyr release was unchanged. Evoked release of 3H-ACh and all amino acids except Tyr showed substantial Ca2+ dependence. A significant (p less than 0.05) age-related reduction in both basal (-35%) and K(+)-stimulated (-42%) efflux of GABA from the CIC was observed. A corresponding decrease in postrelease tissue content of GABA in CIC of aged rats was observed (-30%, p less than 0.05). In contrast, tissue content as well as basal and evoked release of Glu, Asp, Tyr, and 3H-ACh was similar between the 2 age groups. Age-related GABA neurochemical changes described in the CIC were not observed in the release of the other amino acids or 3H-ACh from either the rostral ventrolateral medulla or the somatosensory cortex, 2 brain regions involved in processing non-auditory sensory input. These data support previous findings that GABA, Glu, Asp, and ACh may subserve neurotransmission in the CIC. Additionally, these data provide clear evidence for a pronounced, region- and neurotransmitter-selective, age-related reduction of GABA in the CIC. These findings support the hypothesis that impairment of inhibitory GABAergic neurotransmission in the CIC may contribute to abnormal auditory perception and processing seen in neural presbycusis.

1. The role of GABAergic inhibitory inputs onto posteroventral cochlear nucleus (PVCN) neurons in the anesthetized chinchilla was investigated through iontophoretic application of the GABAA receptor agonist muscimol and the GABAA receptor antagonist bicuculline. The majority of the neurons studied displayed phasic temporal response patterns. 2. All the neurons were sensitive to bicuculline and displayed an increase in discharge rate, which was greatest during the post-onset portion of the response. Most of the tested neurons were also sensitive to muscimol, which appeared to mimic the putative effect of endogenous GABA. 3. Bicuculline reduced the average first-spike latency and the average variability of the first-spike latency. Muscimol had the opposite effect. 4. Bicuculline did not significantly alter the threshold but rather increased discharge rate at suprathreshold intensities. 5. The width of the excitatory response area was not significantly increased by application of bicuculline. The increase in discharge rate occurred within the units' excitatory response areas. 6. The shape of the rate-intensity functions was not altered by bicuculline application. 7. We conclude that GABAergic inhibitory inputs control the post-onset discharge rate of some PVCN neurons. They may suppress tonic activity, resulting in more phasic discharge patterns.