High-throughput synaptic connectivity mapping using in vivo two-photon holographic optogenetics and compressive...

Area of Science:

• Neuroscience
• Systems Neuroscience
• Computational Neuroscience

Background:

• Understanding synaptic connectivity in neural circuits is crucial for deciphering brain function during behavior.
• Current in vivo synaptic mapping techniques have limited throughput, hindering comprehensive circuit analysis.

Purpose of the Study:

• To develop a framework for significantly increasing the throughput and speed of in vivo synaptic mapping.
• To enable rapid and efficient characterization of neural circuit connectivity in living animals.

Main Methods:

• Combined two-photon holographic optogenetics for presynaptic stimulation with whole-cell recordings for postsynaptic responses.
• Utilized compressive sensing reconstruction for sparse connectivity mapping.
• Applied sequential single-cell stimulation and holographic multi-cell stimulation strategies.

Main Results:

• Achieved rapid probing of connectivity (~5 min for up to 100 cells) in mouse visual cortex.
• Successfully identified synaptic pairs, their strength, and spatial distribution.
• Demonstrated improved sampling efficiency and connection recovery with multi-cell stimulation and compressive sensing, reducing measurements by threefold.

Conclusions:

• The developed framework offers higher throughput for in vivo neural circuit analysis.
• This approach provides deeper insights into brain structure-function relationships.
• The method has the potential to accelerate discoveries in systems neuroscience.