The brain is organised into structures that span a wide range of spatial scales. These include very small synaptic junctions that connect neurons together, through to larger brain structures such as the neocortex and cerebellum. “To understand how the brain represents sensory and motor information, and learns and performs cognitive tasks, we need to be able to measure signals as they flow through neural circuits,” explains 3DSCAN project coordinator Angus Silver, professor of Neuroscience at University College London, United Kingdom. To do this, neuroscientists increasingly use two-photon microscopy, a particular type of fluorescence microscopy. “Multiphoton fluorescence imaging techniques allow scientists to ‘visualise’ neural activity in brain circuits while an animal is performing a behavioural task,” says Silver.
Even with the application of such cutting-edge technology, measuring brain activity remains extremely complicated. A key challenge is that conventional two-photon microscopes generate 2D images, and are slow in focussing to different depths. “A main focus of my research is on understanding how the cerebellum and neocortex represent and process sensory and motor information during the acquisition of skilled behaviours,” notes Silver. “While two-photon microscopy provides the best tool to study the structure and function of the brain at the synaptic, neuronal and circuit level, I felt that monitoring activity in 3D brain circuits required better temporal resolution.” To overcome this, and with the help of a previous EU grant, Silver and his team developed 3D scanning technology, centred around an acousto-optic lens (AOL). This consists of four acousto-optic deflectors arranged in a series, which are then incorporated into a two-photon microscope. A project team consisting of electrical engineers, physicists, computer programmers and experimentalists built and trialled the innovation, and were able to verify its efficacy. “We found that we could now selectively scan fine 3D neuronal structures, such as dendritic trees, at high speed,” explains Silver. The non-linear AOL 3D scanning technology has been patented by UCL Business.
The objective of the most recent 3DSCAN project was to build on this success, and to facilitate the commercialisation of this innovative 3D scanning technology. This was achieved through providing IP protection support, refining low-cost manufacturing techniques and exploring potential markets and likely industrial partners in microscopy, biosciences and beyond. “This grant enabled Agile Diffraction, a UCL spin-off company, to sign an exclusive licence agreement with UCL Business for access to the key IP to commercialise and sublicense the technology,” says Silver. “The AOL 3D scanner manufacturing process has since been tested, and founder investment used to acquire inventory to start building AOL laser scanners.” While the two-photon microscope has become a major instrument in the toolbox of neuroscientists, Silver believes that this 3D technology will effectively extend this functionality further. The scanner is now commercially available, and the company is engaging with individual scientists keen to purchase 3D AOL scanners for their labs and institutions. A key benefit of this scanning technology is that it can be added to existing two-photon microscopes. “The history of neuroscience shows that our understanding of the brain has largely been limited by the technology available,” he adds. Silver is confident that the non-linear AOL 3D scanner will accelerate the pace of discovery in circuit research, bringing us closer to developing new treatments for neurological diseases and disorders.
3DSCAN, brain, neural, microscopy, biosciences, neurons, sensory, neuroscience