Quantifying the Organization of Mitochondria Within a Connectome

Date of Award

Spring 1-1-2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Molecular, Cellular, and Developmental Biology

First Advisor

Clark, Damon

Abstract

The central question in systems neuroscience is: how does the brain compute? Thestandard approach is to treat a network of neurons as an electrical circuit and model their responses. However, neurons are not pieces of metal embedded in a circuit. Neurons are biological cells with organelles that are required for their computational function. Mitochondria are critical for neurons to form branches, change radii, and elongate; all of which change how signals are processed in the brain. With mitochondria playing a key role in neural computation, we sought to understand how mitochondria are organized in the brain. Recent advances in connectomic research have made large, electron microscopy datasets publicly available to discover principles of mitochondria organization. We investigate the distribution of millions of mitochondria in the Drosophila hemibrain dataset, 100s of times larger than previous mitochondria datasets. The significant increase in statistical power has allows us to uncover rules of mitochondria placement and a new interpretation of the connectome conditioned on mitochondria placement. Our results reveal a quantitative framework for understanding how subcellular components are organized in the brain and correlating these principles with neural function.

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