Wormspy: Watching the Worm Brain Move

Show notes

Welcome to the next episode of The Worm Podcast 🔬

Today we are looking at a new imaging system called Wormspy.

The problem it tackles is a familiar one in neuroscience:

how do you record what neurons are doing without stopping the animal from behaving normally?

Many high-resolution imaging systems restrain the worm, compress it, or use complex microscope setups that can alter behaviour.

Wormspy takes a different approach. It is a low-cost, open-source epifluorescence microscope designed to track freely moving C. elegans while recording fluorescence and behaviour at the same time.

🤖 How Wormspy works

The system uses two cameras and a motorised XYZ platform.

One channel records fluorescence, while the other tracks the worm and its behaviour.

Instead of moving the animal, Wormspy moves the microscope around a fixed behavioural arena to keep the worm centred and in focus.

The software supports manual tracking, threshold-based automatic tracking and DeepLabCut integration, with automatic focus correction during recording.

🧠 Watching neurons during real behaviour

The authors demonstrated Wormspy across several different experiments.

They recorded body-wall muscle calcium activity during locomotion and reproduced the known deeper body bends of gar-3 mutants.

They then imaged the ASH sensory neuron as worms encountered an aversive glycerol barrier.

ASH activity rose as the worms entered the barrier and peaked around the start of the reversal response.

🍽️ Neurons at the edge of food

The system was also used to image the food-sensing AWC neuron while worms moved around a bacterial lawn.

As the worm’s nose left the food patch, AWC activity increased.

That is exactly the sort of experiment that becomes difficult when the animal is restrained.

Wormspy lets researchers connect neuronal activity directly to where the worm is and what it is doing.

🔬 Imaging inside a neuron

Perhaps the most impressive demonstration was in the RIA interneuron.

Wormspy could resolve calcium events in separate regions of the RIA axon while the worm moved freely.

Those local calcium signals tracked dorsal and ventral head movements.

Interestingly, the timing differed slightly from previous measurements in restrained animals, suggesting that the imaging setup itself can influence the behaviour being measured.

🛠️ Why this matters

Wormspy is:

open-source × modular × relatively low-cost × behaviour-friendly

It can also be adapted for different fluorophores, optogenetic stimulation and other small organisms.

The aim is not simply to make microscopy cheaper.

It is to make high-resolution neural imaging more accessible while preserving the natural behaviour that researchers actually want to understand.

🧠 The take-home message

If you want to understand the relationship between a neuron and a behaviour, ideally you should watch both at the same time.

Wormspy makes that possible without forcing the worm to stay still.

Sometimes the best way to understand the worm brain is simply to let the worm move.

📄 Paper discussed

Sebastian N. Wittekindt, Hannah Owens, Aurélie Guisnet, Lennard Wittekindt and Michael Hendricks (2026)

An epifluorescence microscope design for naturalistic behavior and cellular activity in freely moving Caenorhabditis elegans

Nature Communications, 17:4411

DOI: https://doi.org/10.1038/s41467-026-72709-w

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