Thank you @katrinvogt.bsky.social! I had a great time with all the impressive science going on in Konstanz!

We thank @dfg.de and the #NeuroNex program for generously funding our work, and our neighbours and colleagues at @uni-wuerzburg.de, especially the Department of Neurobiology and Genetics (Charlotte Förster, Chris Wegener, and @silkesachse.bsky.social).
Stay tuned - more walking papers on the way...

This study was a team effort, with some surprises and directional changes on the way. I am grateful to the entire crew, especially Stefan & Sander, Fathima, Feffo, Mert, and Aleyna from my lab, Adrián and @postpop.bsky.social from the Clemens Lab, and Axel and Ansgar from the Büschges lab.

Both MDN and DopaMeander are gated out (switched off) during flight. Showing that behavioral state-dependent gating occurs simultaneously across levels of motor control and is bidirectional in nature, allowing the specific boosting of motor control modules in the appropriate behavioral context.

Finally, we leveraged the fact that we identified neurons controlling walking across hierarchical levels to ask how the brain ensures that appropriate motor output is generated in different behavioral states. To do so, we recorded MDN and DopaMeander in flies transitioning into and out of flight.

DopaMeander, in contrast, contributes to forward walking, but its activity is particularly linked to turning in the ipsiversive direction - so that the right DopaMeander contributes to rightward turns, and the left DopaMeander to leftward turns...

We quantified this by building linear-nonlinear models which estimate how, precisely, each neuron controls walking parameters. It turns out MDN does not simply ‘switch’ the walking direction but encodes a backward walking drive that increases from forward walking, to stopping, to backward walking.

We then performed patch-clamp recordings from DopaMeander and MDN in spontaneously walking flies. DopaMeander is more active during forward walking, whereas MDN is more active during backward walking – as predicted from the phenotypes of both neurons. Hence, they control opposite walking regimes.

Why get excited about this? Dopamine is tightly linked to motor control in the vertebrate nervous system. In flies, dopamine is strongly linked to learning and memory and decision-making processes, but less so to motor control or walking (one great exception here: tinyurl.com/3xx88j37).

Activation, silencing and stochastic labeling experiments reveal that DopaMeander drives forward walking and turning. It is also required for fast walking - flies with silenced DopaMeander walk and turn much less when facing an optomotor stimulus, which induces walking in circles in controls.

Here, we identified a novel, dopaminergic cell type in the brain which drives forward walking – DopaMeander. Connectome analyses reveal DopaMeander modulates a circuit in a specific brain region (the AVLP), which integrates mechanosensory cues from the legs, and includes walking-related neurons.

Next, we turned our attention to forward walking – the preferred way for flies to get around in the world (some argue ‘flies’ should really be called ‘walks’). Forward walking is more versatile and accordingly controlled by larger populations of neurons across complex sensorimotor hierarchies.

We demonstrate that this switch in walking direction is driven by Moonwalker Descending Neurons (MDNs) – which were originally discovered by @salilbidaye.bsky.social. Our patch-clamp recordings show MDNs encode antennal touch. MDNs are also required for antenna-driven backward walking.

First, we looked at backward walking, which typically occurs in response to a threat – or when animals bump into an object or a conspecific. To simulate the sensory stimulus of bumping into something, we poked the antennae of forward walking flies – and found that they reverse walking direction.