Contribution of GABA- and glycine-mediated inhibition to the monaural temporal response properties of neurons in the inferior colliculus

1. To determine the contribution of inhibition to the generation of the temporal response patterns of neurons in the inferior colliculus (IC), the effects of iontophoretically applied gamma-aminobutyric acid (GABA), glycine, and the GABA(A) and glycine receptor antagonists, bicuculline and strychnine were studied on 121 neurons in the IC of urethan-anesthetised guinea pig. 2. The neurons temporal discharge patterns were classified into six categories on the basis of their peristimulus time histograms (PSTHs). 1) Onset units fired at the stimulus onset and could be divided into two subtypes: narrow (1-2 spikes only) or broad (response lasting up to similar to 30 ms). 2) Pauser units had a precisely timed onset peak separated from a lower level of sustained activity by either a marked reduction or complete cessation of firing. 3) Chopper units had three or more clearly defined peaks near stimulus onset or evidence of regularly spaced peaks over the duration of the stimulus. 4) Onset-chopper units had three clearly defined peaks at onset but no sustained firing. 5) On-sustained units had a clearly defined single onset peak followed by a lower level of sustained activity. 6) Sustained units fired throughout the stimulus, but lacked an onset peak. 3. Iontophoretic application of GABA and glycine produced a dose-dependent reduction in firing rate in 76% (42/55) and 79% (11/14) of units, respectively. Application of bicuculline or strychnine increased the discharge rate in 91% (64/70) and 94% (16/17) of neurons, respectively. 4. The effects of bicuculline and strychnine on PSTH class were studied in detail on 70 neurons. Changes in discharge rate were accompanied by changes in PSTH in 49% (34/70) of neurons tested with bicuculline and 41% (7/17) tested with strychnine. Pauser units were the most affected with 69% changing their PSTH class, but some units in all PSTH classes, except the chopper group, exhibited changes in PSTH pattern after application of bicuculline. The majority of units (similar to 50%) that changed PSTH pattern in the presence of bicuculline became chopper units. Units of all PSTH classes could become choppers, but the proportion of units showing this change was dependent on the unit's control response pattern. All seven units that changed PSTH class with strychnine also became choppers. Changes in PSTH, including the appearance of a chopper pattern, did not depend on either a unit's control discharge rate or the magnitude of the change in discharge rate induced by the antagonists. 5. Bicuculline and strychnine had no significant effect on latency for units in the chopper, onset-chopper, onset, pauser, and on-sustained groups. A few sustained and unclassified units that had long predrug latencies did show marked reductions in latency when tested with bicuculline. 6. The majority of units did not fire spontaneously, and neither bicuculline or strychnine produced a significant increase in spontaneous rate. 7. In many units, the changes in firing rate did not occur equally over the duration of the response. Firing rates at the onset and in the last quarter of the sustained response were compared. Three effects of bicuculline and strychnine were observed. For 80% of units the largest change in firing rate occurred in the sustained response, while in 14% of units the change was greatest at onset. The change in onset and sustained firing rate for the remaining 6% of units was equal. The different effects of the antagonists on the onset and sustained components of the response varied with the unit's control PSTH type. This suggests that there are differences in the timing and strength of the inhibitory inputs impinging on different neurons. 8. Histological verification of recording sites was possible for 59/70 units of which 68% were located in the central nucleus of the IC (CNIC). All the reported effects occurred in the CNIC, but similar changes also were seen in the dorsal cortex and external cortex of the IC. 9. We conclude that GABAergic and glycinergic inhibition exerts a strong influence on the temporal firing pattern of collicular units. After the application of either bicuculline or strychnine, the majority of units become choppers, showing that many IC neurons have the capacity to fire with a regular discharge pattern. These inhibitory effects may be mediated both by temporal variations in the interaction of excitatory and inhibitory inputs, or by the influence of these inputs on specific membrane conductances.