Probing inter-areal computations with a cellular resolution two-photon holographic mesoscope.

Area of Science:

• Neuroscience
• Computational Neuroscience
• Biophotonics

Background:

• Brain computation relies on complex, distributed neural networks.
• Understanding inter-areal processing has been limited by technological constraints.

Purpose of the Study:

• To develop a technology for causally testing hypotheses about neural circuit function.
• To enable simultaneous recording and manipulation of neural activity across large brain areas.

Main Methods:

• Development of a two-photon holographic mesoscope.
• Simultaneous neural activity recording and photo-activation with single-cell resolution.
• Demonstration of precise spatial and temporal neuronal activation in one region and readout in downstream regions.

Main Results:

• The mesoscope allows for precise photo-activation of neuronal sequences.
• Downstream effects of targeted neural activation can be observed in multiple brain regions.
• Single-cell precision is maintained across large-scale neural circuit interrogation.

Conclusions:

• The two-photon holographic mesoscope is a novel platform for studying distributed neural circuits.
• Enables unprecedented causal investigation of feed-forward and feed-back processing.
• Advances the study of brain computation at the single-cell level across macroscopic scales.