Pharmacological Evidence of Inhibitory and Disinhibitory Neuronal Circuits in Dorsal Cochlear Nucleus. Kevin A. Davis and Eric D. Young. Department of Biomedical Engineering and Center for Hearing Sciences, Johns Hopkins University, Baltimore, MD 21205.
APStracts 6:0520N, 1999.
The dorsal cochlear nucleus (DCN) is rich in both glycine and GABA inhibitory neurotransmitter systems and the response properties of its principal cells (pyramidal and giant cells) are strongly shaped by inhibitory inputs. For example, DCN principal cells often display highly nonmonotonic (so-called type IV) input-output functions in response to best frequency (BF) tones. In this study, the inhibitory inputs onto the principal cell types and onto response types of known inhibitory interneurons were compared before and during iontophoretic application of the glycine- and GABAA-receptor antagonists, strychnine and bicuculline. Strychnine eliminates the central (on-BF) inhibitory area in type IV units resulting in monotonic BF rate-level curves. Unexpectedly, bicuculline primarily enhances inhibition in principal-cell types; for example, type IV units are inhibited at lower sound levels in the presence of bicuculline. Principal cell types with weaker inhibitory inputs (type IV-T and type III units) are more strongly inhibited in the presence of bicuculline and are usually converted into type IV units. This enhancement of on-BF inhibition by bicuculline suggests a disinhibitory process involving GABAA action on a non-GABAA-ergic inhibitory pathway. This latter pathway is probably glycinergic and involves type II units (deep-layer vertical cells) and/or complex-spiking units (superficial cartwheel cells), because both of these unit types are disinhibited by bicuculline. One intrinsic GABAA source could be the superficial stellate cells in DCN because bicuculline partly blocks the inhibition evoked by somatosensory-stimulated activation of the superficial granule-cell circuitry in DCN. Taken together, the results suggest that glycinergic circuits mediate directly the inhibition of DCN principal cells, but that GABAA-ergic circuits modulate the strength of the inhibition.
Received 28 May 1999; accepted in final form 12 October 1999.
APS Manuscript Number J434-9.
Article publication pending Journal of Neurophysiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 21 December 1999