Intercellular Interactions Promoting Neural Circuit Formation and Function
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Date
2022-10-26
Authors
Heckman, Emily
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
The function of the nervous system – from perception to behavior - relies on the orderlyformation of neural circuits during development. Given that there are billions of neurons in the
human brain, and thus billions of potential circuit configurations, it remains enigmatic how cells
direct their processes to specific brain regions, identify preferred synaptic partners, and form
synaptic connections often with subcellular precision. Moreover, with billions of cells executing
such a complex developmental sequence, what safeguards are in place to ensure that the final
function of the nervous system is robust to variability in any of these steps? In this dissertation, I
describe the establishment of a model system in the larval fruit fly, Drosophila melanogaster,
that enabled the investigation of these questions in the context of a relatively simple nervous
system. Within this model system, I have found that (i) axon guidance cues are sufficient to
direct the targeting of axons to different postsynaptic subcellular domains, (ii) a presynaptic
neuron is competent to form functional synapses across a range of possible subcellular dendritic
domains, (iii) the presence of a presynaptic axon can promote the local elongation of
postsynaptic dendrites, and (iv) presynaptic activity levels can negatively regulate postsynaptic
dendrite elongation neuron-wide. These simple strategies can be employed to form circuits with
consistent cellular memberships, and furthermore, encode flexible cellular responses to variation
in presynaptic targeting and synaptic strengths to ultimately enable robust nervous system
function. This dissertation contains previously published and co-authored material.
Description
Keywords
axon, circuit, dendrite, Drosophila, synapse