All-optical interrogation of millimeter-scale networks and application to developing ferret cortex

Area of Science:

• Neuroscience
• Systems Neuroscience
• Optical Imaging and Stimulation

Background:

• Neural circuits spanning millimeters are crucial for perception and behavior.
• In vivo calcium imaging and optogenetics are powerful tools for studying large-scale neural networks.
• Simultaneous measurement and manipulation of millimeter-scale neural circuits are needed.

Purpose of the Study:

• To introduce a novel opto-macroscope system.
• To enable artifact-free, all-optical, simultaneous large-scale neural imaging and optogenetic stimulation.
• To investigate millimeter-scale neural circuits.

Main Methods:

• Developed an opto-macroscope, an all-optical system.
• Achieved patterned optogenetic stimulation with high spatial and temporal resolution across millimeters.
• Enabled simultaneous imaging of functional neural activity.

Main Results:

• Demonstrated direct manipulation of cortical regions from hundreds of microns to several millimeters.
• Showcased perturbation of individual brain areas and functional networks.
• Successfully reactivated complex neural networks in developing ferret visual cortex using patterned optogenetic stimuli.

Conclusions:

• The opto-macroscope extends current all-optical and mesoscopic optogenetic techniques.
• It overcomes limitations of cellular-scale multiphoton stimulation and techniques lacking simultaneous readouts.
• Provides a powerful tool for investigating the role of cortical domains in neural networks underlying perception and behavior.