Graduation Year

2020

Document Type

Thesis

Degree

M.S.B.E.

Degree Name

MS in Biomedical Engineering (M.S.B.E.)

Degree Granting Department

Biomedical Engineering

Major Professor

George Spirou, Ph.D.

Committee Member

Paul Manis, Ph.D.

Committee Member

Joseph Walton, Ph.D.

Keywords

auditory processing, electron microscopy, neural circuits, sound localization, three-dimensional modeling

Abstract

Globular bushy cells (GBCs) of the cochlear nucleus are specialized neurons that encode the temporal features of sound. Multiple auditory nerve inputs are known to synapse onto a single GBC, but the exact number and sizes of these inputs have not been systematically investigated in adult mice. To gain a high-resolution and unbiased look at the auditory inputs contacting GBCs, our lab utilized Serial Block-Face Scanning Electron Microscopy. Specifically, 21 GBCs and all their large inputs were reconstructed at nanometer resolution. To produce the most precise results, we applied careful attention to the reconstruction and implemented cutting-edge meshing algorithms. We found that a range of 5 – 12 large auditory nerve terminals converge onto each GBC, which is higher than previously reported electrophysiological estimates. Interestingly, some GBCs were found to have a single large, dominant input, whereas others did not. Thus, we conclude that there are two models of GBC innervation, i.e., a mixed model (1 or 2 suprathreshold inputs and multiple subthreshold) and a coincidence detection model (all subthreshold inputs). The detailed reconstructions were then combined with a GBC computational model which confirmed the presence of two innervation models. We also present novel discoveries about the structure of GBCs that could only be seen in volume electron microscopy.

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