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Chronic, cortex-wide imaging of specific cell populations during behavior.

Joao CoutoSimon MusallXiaonan R SunAnup KhanalSteven GlufShreya SaxenaIan KinsellaTaiga AbeJohn P CunninghamLiam PaninskiAnne K Churchland
Published in: Nature protocols (2021)
Measurements of neuronal activity across brain areas are important for understanding the neural correlates of cognitive and motor processes such as attention, decision-making and action selection. However, techniques that allow cellular resolution measurements are expensive and require a high degree of technical expertise, which limits their broad use. Wide-field imaging of genetically encoded indicators is a high-throughput, cost-effective and flexible approach to measure activity of specific cell populations with high temporal resolution and a cortex-wide field of view. Here we outline our protocol for assembling a wide-field macroscope setup, performing surgery to prepare the intact skull and imaging neural activity chronically in behaving, transgenic mice. Further, we highlight a processing pipeline that leverages novel, cloud-based methods to analyze large-scale imaging datasets. The protocol targets laboratories that are seeking to build macroscopes, optimize surgical procedures for long-term chronic imaging and/or analyze cortex-wide neuronal recordings. The entire protocol, including steps for assembly and calibration of the macroscope, surgical preparation, imaging and data analysis, requires a total of 8 h. It is designed to be accessible to laboratories with limited expertise in imaging methods or interest in high-throughput imaging during behavior.
Keyphrases
  • high resolution
  • high throughput
  • minimally invasive
  • single cell
  • stem cells
  • mental health
  • decision making
  • bone marrow
  • multiple sclerosis
  • atrial fibrillation
  • white matter