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Development, Adaptation, and Stimulus-independent Neural Activity in a Sensorimotor Circuit

Tuesday, October 25, 2022

12:00 PM-2:00 PM

BIOMED PhD Thesis Defense

Development, Adaptation, and Stimulus-independent Neural Activity in a Sensorimotor Circuit in Drosophila Melanogaster
Brennan McFarland, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
Catherine von Reyn, PhD
Assistant Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

In order for the brain to function correctly, neurons must connect with the correct partner neurons. This process is incredibly complex, and faults in this neurodevelopmental program underlie a variety of neurodevelopmental disorders like autism, ADHD, schizophrenia, and intellectual disabilities. Accumulating evidence suggests mutations in genes involved in forming neuronal connections are also implicated in the pathology of neurodegenerative disorders, and disease progression may begin during development prior to presentation of clinical symptoms. Our understanding of developmental mechanisms used to achieve proper connectivity, and how these processes go awry in diseased states, is still rudimentary, highlighting the need for further investigation into neurodevelopment.
A major barrier in studying neural circuit development is the lack of models that allow for reproducible, cell-type specific genetic targeting over development within a well-defined circuit. Functional characterization of neurons across development requires electrophysiology, but there is an additional barrier requiring physical access to neurons. Investigations in vertebrate systems are informative but typically are low-throughput due to lack of genetic accessibility or limited knowledge of the connectome. While invertebrate systems such as Drosophila melanogaster overcome these limitations, current models often focus on wiring within the neuromuscular junction (NMJ) or one-to-one neuron partner pairings in sensory systems. Developmental models of circuits with more complex pairings involving multiple partners are less common. Rarely are both connections between neurons and neural activity studied together across development, limiting our understanding of how neural circuits develop and appropriately function.
In this proposal, we overcome these limitations and characterize the development of a genetically tractable, well-established sensory-motor circuit in the invertebrate animal Drosophila melanogaster. In this circuit, multiple pre-synaptic visual projection sensory neurons (VPNs) converge onto a shared post-synaptic sensorimotor descending neuron (DN). In Aim 1, we characterize the development of converging pre-synaptic VPN inputs to a shared DN and use single-cell RNA-sequencing data to describe how VPN mRNA expression trends related to synaptic genes change over development. In Aim 2 we investigate pre- and post-synaptic puncta appositions during development, and investigate neural activity during development by developing the first ex-vivo pupal electrophysiology preparation. Finally, in Aim 3 we ablate one of the main pre-synaptic VPN inputs to a shared DN and characterize how connectivity and DN functional output change as a result. The visual system of Drosophila shares many strikingly similarities to vertebrate visual systems in terms of structure and function, therefore our findings will be relevant across many systems. Our results demonstrate our model system can be used to investigate complex developmental wiring mechanisms, and can be used to understand how sensory features are represented by sensory neurons and integrated into a sensorimotor network.

Contact Information

Natalia Broz

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