Chronic cellular imaging of mouse visual cortex during operant behavior and passive viewing.

Area of Science:

• Neuroscience
• Cellular Imaging
• Systems Neuroscience

Background:

• Mammalian neocortical neurons exhibit diverse cell types and connectivity, crucial for computation but poorly understood.
• Extracellular recordings in the visual cortex reveal behavioral modulation of neural activity, yet dissecting specific circuit contributions requires new methods.

Purpose of the Study:

• To develop and validate a novel method for three-dimensional (3D) cellular imaging of neural activity in the awake mouse visual cortex.
• To enable the dissection of specific circuit element contributions to visual perception and perceptual learning.

Main Methods:

• Developed a sensitive two-photon calcium imaging microscope for rapid 3D tracking of neurons.
• Recorded cellular calcium activity in head-fixed mice performing visual discrimination tasks over extended periods (hours, days, weeks).
• Utilized both synthetic and genetically encoded calcium indicators, combined with genetic labeling for cell-type identification.

Main Results:

• Demonstrated stable, single-trial resolution recordings of neural activity during operant behavior with minimal artifacts.
• Showcased the ability to track neuronal activity in vivo across multiple days and weeks.
• Validated the method's capacity to identify neuronal classes when integrated with genetic and molecular tools.

Conclusions:

• The developed 3D imaging approach allows in vivo physiological measurements from distinct neuronal classes, enhancing understanding of cortical microcircuits in sensory perception and learning.
• This high-throughput, chronic in vivo assay is applicable to various mouse models of neurological disease, facilitating research into behavioral influences on cellular activity.