Wiring an Escape: Competition and Refinement in a Developing Sensorimotor Circuit

Tuesday, August 10, 2021

12:00 PM-2:00 PM

BIOMED PhD Research Proposal
 
Title:
Wiring an Escape: Competition and Refinement in a Developing Sensorimotor Circuit

Speaker:
Brennan McFarland, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University
 
Advisor:
Catherine von Reyn, PhD
Assistant Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
 
Details:
For our brain to function correctly our neurons must connect with the correct partner neurons and develop their own intrinsic properties. 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 the developmental mechanisms that drive normal development is still rudimentary, and even less is known about how these processes go awry in diseased states, 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. There is the added complexity of needing to physically access neurons across development to perform impactful experiments like electrophysiology. 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. Additionally, across model systems, rarely are both connections between neurons and neuron intrinsic properties 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) wire with a shared post-synaptic sensorimotor descending neuron (DN). In Aim 1, we characterize the development of 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 ablate one of the main pre-synaptic VPN inputs to a shared DN and characterize how synaptic targeting, synaptic density and DN functional output change as a result. Finally, in Aim 3 we characterize how intrinsic properties of VPNs change over development and investigate how they contribute to VPN output across development. 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 will demonstrate our model system can be used 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
njb33@drexel.edu