How does the brain translate what we see into what we do? Every action we take, from catching a ball to avoiding danger, relies on precise connections between neurons. Dr. Mark Dombrovski, previously at the University of California Los Angeles, and now at the University of Colorado Boulder, explores how these neural circuits form, linking the genetic and molecular building blocks of the brain to behaviours. At the heart of his research lies a fundamental question: How do neurons identify and connect with their correct partners to form precise circuits in the developing brain, where they are exposed to so many possible alternative options? Read More
Dr. Dombrovski investigates this question using the visual system of fruit flies. Fruit flies are a simple yet powerful model for understanding how visual signals are converted into movements – a process known as visuomotor transformation.
By examining how fruit flies detect and respond to visual threats, Dr. Dombrovski’s team, in collaboration with Dr. Gwyneth Card from Columbia University, discovered a new brain wiring strategy called Synaptic Gradients.
They found that neurons belonging to the same neuronal type respond differently to visual stimuli depending on the area of visual space they monitor. This difference arises from variations in their wiring: neurons gradually vary in the number of synapses they form with their downstream partners – descending neurons that control escape movements. These synaptic gradients create a neural map translating visual object locations directly into precise movement directions, enabling flies to accurately escape danger.
To understand how such precise wiring occurs at the molecular level, Dr. Dombrovski identified two neuronal recognition molecules – Beat-VI and Dpr13 – that accurately guide developing neurons toward their correct partners. Remarkably, each neuron within its neuronal type expresses these molecules at distinct levels, forming unique molecular identities that determine their connectivity.
For instance, neurons monitoring the dorsal (or upper) visual field express higher levels of Beat-VI and Dpr13, resulting in stronger connections to downstream escape neurons and higher sensitivity to dorsal visual stimuli. As predators often attack from above, the ability to detect movement in this area is vital for survival.
Dr. Dombrovski’s research introduces an entirely new understanding of synaptic partner matching, termed synaptic specificity, where neurons fine-tune their synaptic connections by adjusting gene expression levels.
These findings highlight a continuity between genes and molecules shaping neuronal connectivity and precise wiring of behaviourally relevant neural circuits. By uncovering the molecular mechanisms behind neural connections, this work provides insights into how the brain interprets sensory information and executes accurate responses. These discoveries provide a framework for generating predictive models of brain wiring and deepen our understanding of neural connectivity in both health and disease.
