New Principles for Cell and Circuit Function Revealed by Volume Nanoscale Imaging

Computational properties of neural circuits are determined by the integrative properties and synaptic maps of their cellular elements. This information is challenging to acquire. For example, in the auditory system it is incomplete for even the most studied cell type, the bushy cell (BC). BCs encode temporal fluctuations in sound amplitude, and are important for a range of perceptual abilities including sound localization and communication. Prevailing theory is that one of two subtypes of BCs, called globular BCs, accomplish their task by measuring coincidence of similarly weighted sub‐threshold auditory nerve (AN) inputs using short integration time constants. However, the number and sizes of these inputs are not known, and the synaptic map of dendrites is woefully incomplete. We employed serial blockface scanning electron microscopy (SBEM) of mouse cochlear nucleus to acquire this information. This approach revealed more inputs (mean 7.8, mode 8, range 5–12, n = 15 cells) than estimated using physiological methods (mean 5.1, mode 5, range 4–6, n = 8 cells; Cao and Oertel 2010), and a large range of sizes (35 – 302 μm 2 ), and likely influence on BC activity. We discovered a new dendrite structure, called a hub, which can yield up to 13 branches, and further document frequent and periodic swellings along dendritic processes. We completed the first synaptic map for a BC dendrite system, and revealed that entire branches were non‐innervated. Dendrite branches from the same and adjacent BCs were intertwined, and formed direct membrane contacts. We established a pipeline, using 3D virtual reality software, called syGlass, developed in our laboratory, to skeletonize dendrites and export the structures for compartmental modeling in NEURON. These models permitted activation of AN inputs individually, which revealed that the largest input onto one‐half of cells was supra‐threshold. Therefore BCs do not operate via a simple coincidence model of uniformly weighted sub‐threshold inputs. Dendrites served as a tuned current sink, since their removal rendered even the smallest AN input supra‐threshold. Current work is exploring the presence of electrical contacts at apposition of dendrite membrane, and whether these contacts improve synchrony in activity of BC clusters. Support or Funding Information NIH DC007695 NIH GM103503 NIH GM103412 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .