The Lbx1 lineage differentially contributes to inhibitory cell types of the dorsal cochlear nucleus, a cerebellum like structure, and the cerebellum

1. The amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glycine function as inhibitory neurotransmitters associated with nonprimary inputs onto spherical bushy and stellate cells, two principal cell types located in the anteroventral cochlear nucleus (AVCN). These neurons are characterized by primary-like (including phase-locked) and chopper temporal response patterns, respectively. 2. Inhibition directly adjacent to the excitatory response area has been hypothesized to sharpen or limit the breadth of the tonal frequency receptive field. This study was undertaken to test whether GABA and glycine circuits function primarily to sharpen the lateral edges of the tonal excitatory response area or to modulate discharge rate within central portions of the excitatory response area of AVCN neurons. 3. To test this, iontophoretic application of the glycineI antagonist, strychnine, or the GABAA antagonist, bicuculline, was used to block inhibitory inputs after obtaining control families of isointensity contours (response areas) from extracellularly recorded AVCN neurons. 4. Blockade of GABA and/or glycine inputs was found to increase discharge rate primarily within the excitatory response area of neurons displaying chopper and primary-like temporal responses with little or no change in bandwidth or in off-characteristic frequency (CF) discharge rate. 5. The principal sources of inhibitory inputs onto AVCN neurons are cells located in the dorsal cochlear nucleus and superior olivary complex, which appear to be tonotopically matched to their targets. In agreement with these morphological studies, the data presented in this paper suggest that most GABA and/or glycine inhibition is tonotopically aligned with excitatory inputs. 6. These findings support models that suggest that GABA and/or glycine inputs onto AVCN neurons are involved in circuits that adjust gain to enable the detection of signals in noise by enhancing signal relative to background.

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In Vitro Studies of Neuromodulation and Plasticity in the Dorsal Cochlear Nucleus

The Oxford Handbook of the Auditory Brainstem ◽

10.1093/oxfordhb/9780190849061.013.5 ◽

2018 ◽

pp. 122-142 ◽

Cited By ~ 1

Author(s):

Laurence O. Trussell

Keyword(s):

Synaptic Plasticity ◽

Auditory Processing ◽

Cochlear Nucleus ◽

Cell Types ◽

Auditory Pathway ◽

Dorsal Cochlear Nucleus ◽

Membrane Properties ◽

Auditory Input ◽

Dynamic Tuning

The dorsal cochlear nucleus (DCN), a division of the cochlear nuclear complex, has been the subject of intense interest for its role in auditory processing and hearing disorders. The tonotopic layout of DCN principal cells and the refinement of processing of auditory signals by interneurons are together thought to permit encoding of sound source elevation. However, the many cell types and complex connectivity of the DCN suggest more diverse functions than localization. A prominent non-auditory input to the DCN has been proposed to assist in such functions as orienting to sounds of interest, detecting moving sounds, or cancelling self-generated sounds. Synaptic plasticity in the DCN may be essential for dynamic tuning of non-auditory input. Indeed, long-term changes in synaptic or membrane properties could underlie tinnitus, which is associated with hyperactivity in the DCN in some animal models. Finally, the DCN is invested with wide-ranging neuromodulatory mechanisms, suggesting that changes in the behavioral state of animals associated with such neuromodulatory systems might alter sensory processing at the earliest stages of the auditory pathway. This review will focus on studies that have utilized the in vitro brain slice approach to identify basic mechanisms of synaptic plasticity and neuromodulation in the DCN.

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Pharmacological Evidence of Inhibitory and Disinhibitory Neuronal Circuits in Dorsal Cochlear Nucleus

Journal of Neurophysiology ◽

10.1152/jn.2000.83.2.926 ◽

2000 ◽

Vol 83 (2) ◽

pp. 926-940 ◽

Cited By ~ 55

Author(s):

Kevin A. Davis ◽

Eric D. Young

Keyword(s):

Cochlear Nucleus ◽

Cell Types ◽

Giant Cells ◽

Dorsal Cochlear Nucleus ◽

Principal Cell ◽

Inhibitory Neurotransmitter ◽

Level Curves ◽

Principal Cells ◽

Type Iv ◽

Sound Levels

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 usually are converted into type IV units. This enhancement of on-BF inhibition by bicuculline suggests a disinhibitory process involving GABAA action on a non-GABAAergic 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 GABAAergic circuits modulate the strength of the inhibition.

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