The art of wandering in vertebrates: a new study has mapped the neurons involved in locomotion

For those fortunate enough to walk normally, wandering is such an expected behaviour that we hardly consider that it involves complex, partly involuntary processes.

Martin Carbo-Tano, a post-doctoral fellow at Paris Brain Institute, explained: “Animals move to explore their environment in search of food, interaction with others, or simply out of curiosity. But the perception of danger or a painful stimulus can also activate an automatic flight reflex.”

In both cases, movement initiation relies on the activation of so-called reticulospinal control neurons, which form an intertwined network in the most posterior part of the brain – the brainstem.

These neurons relay nerve signals between the brain and the spinal cord and are essential for motor control of the limbs and trunk and movement co-ordination.

Upstream of the reticulospinal neurons is the mesencephalic locomotor region (MLR), which is also essential for locomotion since, in animals, its stimulation triggers forward propulsion.

It is found in many vertebrates, including monkeys, guinea pigs, cats, salamanders, and even lampreys.

Carbo-Tano said: “Because the role of the MLR is conserved in many vertebrate species, we assume that it is an ancient region in their evolution – essential for initiating walking, running, flying, or swimming.

“But until now, we didn’t know how this region transmits information to the reticulospinal neurons.

“This prevented us from gaining a global view of the mechanisms that enable the vertebrae to set themselves in motion and, therefore, from pointing out possible anomalies in this fascinating machinery.”



Locomotion downstream


Studying movement initiation is a little tricky: neurons located in the brain stem are not easily accessible and observing their activity in vivo in a moving animal proved difficult.

To solve this problem, Martin Carbo-Tano has developed a new approach to stimulate tiny areas in the brain.

Together with Mathilde Lapoix, a PhD student in Claire Wyart’s team at Paris Brain Institute, the researchers took advantage of the transparency of the zebrafish larvae brain to localise the structures involved in locomotion downstream of the MLR and follow the propagation of nerve impulses.

This method, inspired by the work of their collaborator Réjean Dubuc at Montréal University, allowed them to make several remarkable discoveries.

Wyart said: “We observed that neurons in the mesencephalic locomotor region are stimulated when the animal moves spontaneously, but also in response to a visual stimulus.

“They project through the pons – the central part of the brain stem – and the medulla to activate a subpopulation of reticulospinal neurons called ‘V2a’.

“These neurons control the finer details of movement, such as starting, stopping, and changing direction. In a way, they give steering instructions!

“Previous work on mice had revealed that reticulospinal neurons control turning; Martin and Mathilde have discovered the control circuit that triggers forward locomotion.”


Essential step


To better understand the effects of this mechanism on the movements of larval zebrafish, the researchers triggered it experimentally by stimulating the mesencephalic locomotor region.

They observed that the duration and vigour of forward movement correlated with the intensity of the stimulation.

Carbo-Tano said: “Quadrupeds can adopt different gaits, such as walking, trotting, or galloping, but aquatic animals also mark gait transitions.

“We think that MLR has a role to play in this intensification of movement, which we have observed in zebrafish.”

For the first time, this work made it possible to map the neuronal circuits involved in initiating forward movement – a deficient function in patients with Parkinson’s disease.

This is an essential step in shedding light on the motor control mechanisms upstream of the spinal cord.

One day, it may be possible to identify and control all the reticulospinal neurons one by one to model in detail the workings of locomotion and repair those that do not function correctly.

Image: Corticospinal neurons in zebrafish. Credit: Martin Carbo-Tano. CC BY-NC-ND.

Research Aether / Health Uncovered