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

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.