Whole-brain functional imaging at cellular resolution using light-sheet microscopy.

Area of Science:

• Neuroscience
• Systems Neuroscience
• Neuroimaging

Background:

• Understanding complex brain function requires mapping neural communication across the entire central nervous system.
• Current methods often lack the resolution or scope to capture whole-brain activity at the single-neuron level.

Purpose of the Study:

• To develop and demonstrate a novel light-sheet microscopy technique for whole-brain, in vivo neural activity recording in larval zebrafish.
• To identify and characterize functionally defined neural circuits using this high-resolution imaging approach.

Main Methods:

• Utilized light-sheet microscopy to record neural activity from the entire larval zebrafish brain in vivo.
• Employed the genetically encoded calcium indicator GCaMP5G for fluorescence-based activity detection.
• Achieved whole-brain coverage at 0.8 Hz, capturing over 80% of neurons at single-cell resolution.

Main Results:

• Identified two distinct populations of neurons with correlated activity patterns, revealing functionally defined circuits.
• Discovered a circuit linking hindbrain neurons to the spinal cord neuropil.
• Characterized an antiphase oscillating circuit in the anterior hindbrain coupled to the inferior olive on a 20-second timescale.

Conclusions:

• The developed light-sheet microscopy technique enables unprecedented whole-brain, single-neuron resolution recording of neural activity in vivo.
• This approach is powerful for uncovering functionally connected neural circuits and understanding large-scale brain dynamics.
• The identified circuits provide new insights into hindbrain and forebrain communication and oscillatory dynamics.