Date

7-14-2015

Document Type

Dissertation

Degree Name

Ph.D.

Department

Dept. of Physiology and Pharmacology

Institution

Oregon Health & Science University

Abstract

The dorsal cochlear nucleus (DCN) is the earliest site in the auditory system at which multisensory integration takes place. Multisensory inputs do not synapse directly onto the principal cells of the DCN but rather synapse onto an extensive network of interneurons composed of granule, unipolar brush, and Golgi cells. This network is thought to process multisensory signals before ultimately sending some filtered version of the signal to DCN principal cells. The synaptic, cellular, and circuit properties of the multisensory processing network in the DCN are largely unknown, limiting our understanding of the function of multisensory integration in the auditory system. This issue was addressed using paired whole-cell patch-clamp recordings in slices of mouse cochlear nucleus.

Granule cells are known to receive powerful inhibitory inputs, but the source of these inputs and the synaptic pathways driving their activity are unknown. In Chapter 1, I show that Golgi cells provide potent feedback inhibition to granule cells that can be triggered by activity in a single granule cell. Recordings between granule cells and Golgi cells revealed that Golgi cells are the only source of inhibition to granule cells. Golgi cells released GABA and/or glycine onto granule cells, and single Golgi cells were able to inhibit granule cell spiking. Granule cells made glutamatergic synapses onto Golgi cells. Although granule cell synapses onto Golgi cells were initially weak, these synapses facilitated sufficiently with high-frequency spiking that single granule cells were able to evoke Golgi cell spikes in ~40% of paired recordings. As expected from the finding that single granule cells can provide suprathreshold excitation to Golgi cells, bursts of spikes in single granule cells evoked disynaptic IPSCs onto ~5% of neighboring granule cells. Granule cells were also able to evoke disynaptic feedback IPSCs onto themselves in ~6% of recordings.

In Chapter 2, inhibitory synaptic inputs to Golgi cells were investigated. Golgi cells made electrical synapses onto one another, and the main effect of a Golgi cell spike was a prolonged hyperpolarization and reduction in excitability of the coupled Golgi cell. Chemical synapses were found between Golgi cells, but they were nearly 20-fold less common than electrical synapses. In contrast, molecular layer interneurons (MLIs), which also receive glutamatergic input from granule cells, made GABAergic synapses onto Golgi cells. Stimulation of granule cell axons evoked disynaptic

Identifier

doi:10.6083/M4R2106D

School

School of Medicine

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