Glycinergic and GABAergic inputs affect short-term suppression in the cochlear nucleus

Abstract

Most cochlear nucleus (CN) neurons exhibit short-term response suppression to a second stimulus in a paired-pulse (click), forward-masking, paradigm. The magnitude of suppression, which appears to be greater than that observed in acoustic nerve, is dependent on the temporal separation and/or relative intensities of the two stimuli. Recent evidence suggests that inhibitory circuitry ending on CN neurons may mediate this response suppression. Using extracellular recordings from single CN neurons, suppression was evaluated using a forward-masking paradigm. Responses to paired acoustic clicks (i.e., a 'masker' followed by an identical 'probe' click) were measured while the time interval between the masker and probe was varied systematically. The role of inhibitory circuitry in forward-masking in the CN was assessed by pharmacologic manipulation of the GABA(A) and glycine(I) (strychnine-sensitive) receptors. Blockade of glycinergic or GABAergic receptors by iontophoretic application of the antagonists, strychnine and bicuculline methiodide, decreased the effects of forward-masking by shortening recovery times of the probe response in 2/3 of the neurons tested. Conversely, agonist application (glycine, and GABA or muscimol) increased the magnitude of suppression and delayed recovery of the probe response relative to control values. These findings suggest that known circuits releasing glycine and/or GABA mediate short-term response suppression in some CN neurons.