Completed Brain & Nervous System Cells, Biochemistry & Physiology

Miniature microscopes for ultra-high frame rate imaging in freely moving animals

In plain English

AI plain-English summary

A new miniature microscope will capture brain cell activity at speeds ten times faster than current devices, letting scientists watch voltage changes in neurons as animals move freely. The problem is straightforward: the electrical signals that neurons use to compute and communicate happen in milliseconds, but existing miniature microscopes are too slow to see them. Researchers can either immobilise animals for high-speed imaging—which limits what they can learn about natural behaviour—or sacrifice speed for mobility. This project removes that trade-off by using Single Photon Avalanche Diode (SPAD) sensors, which are compact enough to fit on a rodent’s head yet fast enough to record both sub-threshold voltage shifts and action potentials. If successful, the microscopes will allow neuroscientists to link fast electrical signalling in genetically identified neurons to real behaviours like spatial navigation and decision-making. This is fundamental science: it will reveal how neural circuits compute in real time, not just where they are active. The technology could eventually extend beyond neurons to study electrical signalling in other tissues, such as heart or muscle cells. No immediate clinical application is claimed, but understanding how healthy brains process information is the foundation for future work on disorders where that processing goes wrong.

View original technical description
We propose to develop the first miniaturised microscopes for high-speed (kHz) voltage imaging in freely moving animals. Voltage changes that mediate neuronal computations, and electrical signalling in non-neuronal tissues, are too fast to observe with miniature microscopes currently used for imaging in freely moving animals. To address this, we will build miniature microscopes that use Single Photon Avalanche Diode (SPAD) sensor technology to obtain frame rates > 10 fold higher than existing systems. Our proof-of-principle ex-vivo data shows that SPAD sensors can image sub-threshold and spiking activity of neurons reported with genetically encoded voltage indicators (GEVIs). As the sensors used for these experiments have a similar footprint to the standard CMOS sensors in current miniature microscopes, it will be feasible to use SPADs to image fast electrical signalling even in freely behaving animals. Our goals are: 1. To develop miniature microscopes that incorporate our established SPAD technology, along with custom made drivers and control software, to image 10s of neurons in freely moving animals. 2. To develop a second system using state-of-the-art SPAD sensors to image 100s of neurons in freely moving animals. 3. To validate the systems by recording from genetically identified neurons during spatial exploration and action selection.

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Researchers

Benjamin Grewe (EPMC Awardee)Ian Duguid (EPMC Awardee)Istvan Gyongy (EPMC Awardee)Matthew Nolan (EPMC Awardee)Robert Kerr Henderson (EPMC Awardee)Srinjoy Mitra (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Optical Oscilloscope: Real-time, high-throughput, volumetric voltage imaging
Super-resolution multiphoton imaging of synaptic transmission
MICA: High speed, high resolution imaging of excitable cell networks
Two-photon Light Field with Neuro-active Sensing for Fast Volumetric Neural Microcircuit Readout
Fast and Flexible Imaging of Excitable Tissues

Original classification

Technology Development Grant

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