Originally published in March 2024 alongside the preprint, this article was updated in November 2026 to reflect the published research, now available in eLife.

Optogenetic tools have become vital in neuroscience. By shining light into the brain, neuroscientists can transiently turn neurons on and off to elucidate the causal mechanisms underlying animal behaviour. Traditionally, thin optical fibres have been used to deliver light into specific parts of the brain. And while a lot has been learned from this technique, there are several limitations to using optical fibres to deliver light, including that they cannot easily be moved once implanted.

Researchers at the Sainsbury Wellcome Centre came up against this problem during an experiment where the outcome they expected was seen in some animals but not others. They suspected this was because the fibre placement across different mice was variable, leading to differences in experimental effect. The researchers worked closely with the Advanced Microscopy team at SWC to develop a ‘random-access’ system capable of stimulating a wider selection of neurons close to each other. The system they developed, called Zapit, consists of a focused beam of light that can be directed across the entire cortex of the mouse brain very quickly using a pair of scan mirrors. 

“Zapit solves two problems. Firstly, you can stimulate any bit of mouse cortex on the dorsal surface that you like, and you can stimulate multiple areas in close succession. This means you can do more than one experiment in the same animal. Secondly, the system democratises access to this technique, as there is currently no option that you can purchase and the published papers using similar approaches do not provide sufficient detail for non-experts to build a system,” explained Dr Rob Campbell, Head of Advanced Microscopy at SWC and corresponding author on the eLife paper. 

Developing a shareable solution

Dr Campbell worked together with researchers across multiple labs at SWC and UCL to develop a user-friendly solution. The new system, called Zapit, works by targeting locations based on an atlas of brain areas in transgenic mice that express optogenetic actuators in populations of cortical neurons. No permanent implants in the brain are needed.

“Zapit is effectively a programmable laser pointer for switching on and off brain areas in the cortex to understand what role they play in behaviour. Users are able to select areas of the brain from a brain atlas, and then choose how many spots the beam of light targets one after the other. They can then use a simple programming interface to integrate with their behavioural experiments,” explained Dr Campbell.

The system is open source and the team have shared a full parts list, step-by-step assembly instructions, CAD models, and a user-friendly suite of software tools and installation guidelines on GitHub. The software facilitates simple calibration and control of photostimulation and integration of the Zapit system with other multi-platform experimental set-ups. The team are available to contact for anyone who wishes to seek help in setting up a Zapit system.

Overview of the Zapit experimental system: Zapit combines flexible hardware and optical designs with user-friendly control software for calibration, stimulus design and photostimulation control. Together, these components provide researchers with the tools and guidance needed to build their own versatile and powerful laser-scanning optogenetics system, enabling causal investigations of the neural mechanisms driving behaviour.

Implications of Zapit

Zapit has already been used by a number of researchers at SWC, including Sir Henry Wellcome Postdoctoral Fellow, Dr Michael Lohse and Wellcome Trust Early Career Research Fellow, Dr Oliver Gauld. Both are co-first authors who were instrumental in developing the system.

“Using Zapit to inactivate multiple cortical areas in the same behavioural session, we have been able to identify areas in frontal cortex located in close proximity that serve completely different behavioural functions. This has allowed us to uncover new parallel cortico-basal ganglia circuits subserving distinct behavioural subcomponents during decision-making,” explained Dr Lohse.

“The versatile system has been integral to our recent work examining value and action processing within and across cortical areas during economic decision-making,” commented Dr Gauld.

The team hope that the system will continue to enable researchers to carry out more complex experiments. “Zapit helps to reduce the number of animals needed for experiments as it takes away the potential problem of optical fibre misplacement and allows researchers to stimulate multiple areas of the cortex in the same animal,” commented Dr Campbell.

Validating Zapit

The initial iteration of this work was shared as a preprint in 2024, making the Zapit system and its design available to the research community. Since the original preprint was released, the team have adapted the hardware design, ensuring the system can be assembled from readily available commercial parts, and carried out rigorous additional experiments to validate Zapit's performance. Electrophysiological recordings demonstrate that the system can reliably manipulate cortical activity with comparable efficacy to similar published systems, while cortical photoinhibition experiments, performed across multiple SWC labs, further highlight its utility for revealing the causal roles of different sensory and motor cortical regions in awake behaving mice.

The team hopes that making Zapit fully documented and open source will encourage other researchers to adopt and further develop random-access laser-scanning optogenetics. Their aim is to lower the technical barriers to using the approach in laboratories around the world.

About Zapit

To find out more about Zapit:

• Read the paper in eLife: Open source laser-scanning photostimulation for neuroscience with Zapit
• Access Zapit parts list and code on GitHub: Zapit Optostim
• Contact Rob Campbell for more information