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Advanced Circuit and Cellular Imaging Methods in Nonhuman Primates.

Stephen L Macknik1, Robert G Alexander2, Olivya Caballero2

  • 1State University of New York Downstate Medical Center, Health Science Center at Brooklyn, New York 11203, macknik@neuralcorrelate.com.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|October 18, 2019
PubMed
Summary

Advanced imaging tools now allow unprecedented analysis of neural circuits in nonhuman primates (NHPs). These new methods enable long-term studies of brain activity relevant to human cognitive development.

Keywords:
Adeno-Associated viruscortical mappingoptogeneticsprosthetic visiontwo-photon microscopyvoltage-sensitive dye imaging

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Area of Science:

  • Neuroscience
  • Primate Research
  • Advanced Imaging Techniques

Background:

  • Genetically encoded tools and advanced microscopy have transformed neural circuit analysis in rodents.
  • Technical challenges previously limited these methods in nonhuman primates (NHPs).
  • Recent breakthroughs are overcoming these barriers, enabling sophisticated NHP brain research.

Purpose of the Study:

  • To present recent imaging advances in nonhuman primate (NHP) research.
  • To highlight technical developments in optogenetics and various imaging modalities.
  • To showcase the visualization of tens of thousands of cortical neurons in NHPs.

Main Methods:

  • Development of ultra-large imaging windows for NHP cortex.
  • Utilizing long-term imaging chambers for extended neural circuit interrogation.
  • Employing optogenetics, voltage-, calcium-, and glutamate-sensitive dye imaging.
  • Implementing two-photon and wide-field optical imaging techniques.
  • Advancements in viral delivery and genetic expression of indicators and light-activated proteins.

Main Results:

  • Ultra-large imaging windows exceed the size of the entire rodent brain.
  • Imaging chambers allow for long-term studies exceeding a typical mouse lifespan.
  • Visualization of tens of thousands of identified cortical neurons in macaques and marmosets.
  • Successful application of advanced optogenetics and imaging in NHP models.

Conclusions:

  • Current research has overcome previous technical hurdles in NHP neural circuit analysis.
  • Methodological advances in NHPs, such as ultra-large imaging windows, surpass earlier techniques.
  • These advancements facilitate unprecedented large-scale circuit analysis and long-term studies relevant to human cognition.