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Circuit Mechanisms and Molecular Determinants of a Visuomotor Transformation (VMT)

Wednesday, May 22, 2024

2:30 PM-4:00 PM

BIOMED Seminar

Circuit Mechanisms and Molecular Determinants of a Visuomotor Transformation (VMT)

Mark Dombrovski, PhD
Postdoctoral Associate, Zipursky Lab
University of California, Los Angeles; Howard Hughes Medical Institute

Using interdisciplinary approaches (EM-connectomics, single-cell transcriptomics, genetics and physiology), Dr. Dombrovski and colleagues investigate how vision is transformed into action in the fruit fly brain.

Visuomotor transformation (VMT), a vital process by which the brain translates vision into action, requires precise synaptic connectivity between sensory and motor neural circuits. However, the developmental and molecular underpinnings of VMT remain poorly understood. We address this gap by examining the visuomotor interface in Drosophila, leveraging single-cell transcriptomics, EM-connectomics, genetics, and functional approaches to causally link genes and molecules with circuit function.

In our earlier work, we uncovered a novel wiring mechanism governing VMT known as synaptic gradients. This mechanism, operating between feature-detecting Visual Projection Neurons (VPN) and premotor Descending Neurons (DN), transforms object locations in the eye coordinates into directional body movements. Notably, synaptic gradients are independent of axonal and dendritic topography: individual neurons of the same VPN cell type exhibit gradients of synaptic weights with specific DNs reflecting visual field region they sample. This within-cell-type synaptic specificity results in the conversion of a visual space map into a gradient of synapses, representing a fundamentally new mechanism of neuronal connectivity.

But how do synaptic gradients emerge amid lack of spatial cues? Through single-cell transcriptomic analysis of VPNs during development, we discovered significant transcriptomic heterogeneity across individual neuronal types. Spatial gradients of Cell Adhesion Molecules (CAMs) regulating synaptic specificity, topographically aligned with synaptic gradients. We show that within-cell-type molecular gradients of DIP/Dpr and Beat/Side families of CAMs regulate axonal and dendritic synaptic gradients in looming escape and motion detection circuits, respectively. Thus, we propose a model where CAM gradients determine within-cell-type synaptic specificity independently of axonal and dendritic spatial organization. Ongoing functional experiments aim to validate this model.

This work expands our understanding of VMT origins, raises questions about cell type definition, and underscores the importance of multiomic approaches in deciphering the logic of brain wiring.

Mark Dombrovski, PhD, received his BS degree in Biochemistry from Moscow State University in Russia in 2012, following which he dedicated two years to research at the Russian Center for Pediatric Oncology and Immunology, focusing on innovating anti-cancer drug delivery methods.

In 2014, Dr. Dombrovski started a PhD program in Neurobiology at the University of Virginia, supported by a Jefferson Fellowship under the mentorship of Barry Condron. Over five years, he investigated neural mechanisms underlying social behavior and introduced a new experimental model system featuring cooperative foraging behavior in fruit flies, which shed light on how socially relevant traits emerge during critical developmental windows.

After graduating in 2019, Dr. Dombrovski started a postdoc at the laboratory of Larry Zipursky, focusing on circuit wiring mechanisms in the fly visual system. His proposal to establish a new model system investigating synaptic connectivity patterns in the fly visuomotor interface received recognition through the Helen Hay Whitney postdoctoral fellowship. Collaborating with Dr. Gwyneth Card, Dr. Dombrovski uncovered a novel wiring strategy governing visuomotor transformations, prompting further investigation into its molecular determinants. He is now looking to establish his own Research Laboratory that will focus on further understanding the molecular origins of neuronal connectivity underlying complex behaviors.

Contact Information

Carolyn Riley

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Papadakis Integrated Sciences Building (PISB), Room 104, located on the northeast corner of 33rd and Chestnut Streets.


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