Neuroscience at the Nanoscale: Insights into Auditory Development through 3D Reconstruction
The calyx of Held (CH) – principal cell (PC) connection in the medial nucleus of the trapezoid body (MNTB) of the mouse provides a valuable model system to examine these questions, due to its short developmental window (<72 hours), large terminal size, and a clear mono-innervated endpoint. However, unlike other similar model systems, it has been a long-standing question whether this connection undergoes competition during development. We investigated the innervation state of PCs using the novel technique of segmentation and 3D reconstruction of PCs and their associated inputs across important developmental timepoints (P2-9). This technique allowed us to demonstrate early exuberant innervation of PCs (P2), establish that competition is a common process, and pinpoint the 24-hour period from P3-P4 as a uniquely active day in CH growth during which terminal contact with PCs increase at a rate exceeding 300 μm2/day. The extensive morphological information provided by 3D reconstructions also allowed us to undertake a quantitative study of polarity in CH development; developing principal cells are characterized by eccentrically-placed nuclei that appear to define a unique territory amenable to terminal growth opposite the nucleus.
Additionally, this area is enriched in dendrites, and is selectively enlarged as the principal cell matures to create glial process-free surface area for innervation. To our knowledge, this is the first report of a polarity program in the coordinated pre- and postsynaptic development of a non-laminar brain region. Taken in totality, these results suggest a highly polarized, systemic competitive process in the MNTB during the development of the calyx of Held and suggests potential mediators of competition that deserve further study.
Paul Holcomb defended his PhD in 2018 in Neuroscience at West Virginia University under Dr. George Spirou. He received a B.S. in biomedical engineering in 2005 from Vanderbilt University, and spent 5 years in industry at Breault Research Organization researching optical simulation of tissue. His current research focuses on mechanisms which influence the outcome of synaptic competition within the developing central nervous system. Paul resides in Morgantown, WV, with his wife, Micky, and two children, Colin and Isabel.