Simultaneous brain-wide single-cell recording resolves spatiotemporal memory architecture

Area of Science:

• Neuroscience
• Molecular Biology
• Bioengineering

Background:

• Mammalian brain functions rely on coordinated activity across large-scale neural networks.
• Understanding these networks in health and disease requires simultaneous, brain-wide single-cell activity measurement.
• Current live-measurement techniques face limitations in balancing spatial resolution and scale.

Purpose of the Study:

• To introduce GLOBE (sinGle-cell spatiotemporaL recOrding Brain-widE), a novel technology for in vivo, brain-wide single-cell recording.
• To demonstrate GLOBE's capability for high-resolution, sensitive, and scalable measurement of cellular activity.
• To apply GLOBE to map brain-wide neural activity dynamics during fear learning and memory retrieval.

Main Methods:

• GLOBE utilizes genetically encoded intracellular protein tape recorders for analog signal recording.
• A high-throughput computational platform integrates image and signal analysis for accelerated readout.
• Standard light microscopy is used for in situ readout, compatible with expansion microscopy and RNA analysis.

Main Results:

• GLOBE recorded Fos transcriptional activity in up to 219,703 neurons across a mouse brain over 5.5 days.
• Achieved timestamp precision of 3.1-6.7 hours and high local recording density (69-90% of neurons per field of view).
• Revealed brain-wide spatiotemporal structure of Fos activity, showing region-specific temporal heterogeneity in fear learning and memory retrieval.

Conclusions:

• GLOBE provides unprecedented spatiotemporal resolution for brain-wide single-cell activity recording.
• The technology resolves distributed neural dynamics, with variance scaling down as cell numbers increase.
• GLOBE offers broad applications for dissecting physiological and pathological processes at the brain-wide scale.