Circuit mechanisms underlying sensory-evoked navigation

Life-threatening cues such as the scent of smoke or the taste of rotten food cause avoidance behavior in animals.

In such situations, instantaneous integration of relevant sensory inputs by motor centers that guide navigation can be a matter of life and death. How is this sensorimotor integration achieved?

In vertebrates, it is known that motor command centers in the brainstem receive direct inputs from higher brain areas and cutaneous sensory pathways and in turn control the spinal circuits that drive locomotion.

It is less well understood whether these brainstem command neurons are simple integrators relaying information, or whether they add a layer of integration to select locomotor action sequences.

Because brainstem neurons are difficult to visualize and access in mammals, it has been challenging to measure their activity in moving animals as they respond to sensory cues.

In contrast, larval zebrafish is a simpler vertebrate model in which optical technologies can be leveraged to visualise, record, and manipulate any and/or all brainstem neurons during locomotion.

This project will decode the neuronal computations of descending command neurons that integrate sensory inputs and elicit locomotor actions in freely-moving zebrafish larvae.

To this end, my group has designed an unbiased method for segmenting locomotor action sequences from noisy behavioral data.

Applied to robust assays where larvae navigate in chemical gradients, we are now in a unique position to link locomotor action sequences to the sensory landscape fish perceive.

This original approach, together with innovative technologies pioneered in my lab, will reveal brainstem neuronal connectivity and roles in the selection of locomotor sequences.

The EXPLORATOME project will lead to models of circuit computations in the brainstem, a brain region historically-overlooked and with high potential for targeted electrical stimulations in patients with motor disorders.