The need for calcium imaging in nonhuman primates: New motor neuroscience and brain-machine interfaces

Exp Neurol. 2017 Jan;287(Pt 4):437-451. doi: 10.1016/j.expneurol.2016.08.003. Epub 2016 Aug 7.


A central goal of neuroscience is to understand how populations of neurons coordinate and cooperate in order to give rise to perception, cognition, and action. Nonhuman primates (NHPs) are an attractive model with which to understand these mechanisms in humans, primarily due to the strong homology of their brains and the cognitively sophisticated behaviors they can be trained to perform. Using electrode recordings, the activity of one to a few hundred individual neurons may be measured electrically, which has enabled many scientific findings and the development of brain-machine interfaces. Despite these successes, electrophysiology samples sparsely from neural populations and provides little information about the genetic identity and spatial micro-organization of recorded neurons. These limitations have spurred the development of all-optical methods for neural circuit interrogation. Fluorescent calcium signals serve as a reporter of neuronal responses, and when combined with post-mortem optical clearing techniques such as CLARITY, provide dense recordings of neuronal populations, spatially organized and annotated with genetic and anatomical information. Here, we advocate that this methodology, which has been of tremendous utility in smaller animal models, can and should be developed for use with NHPs. We review here several of the key opportunities and challenges for calcium-based optical imaging in NHPs. We focus on motor neuroscience and brain-machine interface design as representative domains of opportunity within the larger field of NHP neuroscience.

Keywords: Brain-machine interfaces; Calcium imaging; Macaque; Motor cortex; Motor system; Neural circuits; Neural computation; Nonhuman primates; Population dynamics; Prosthetics.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Bacterial Proteins / analysis
  • Bacterial Proteins / genetics
  • Behavior, Animal
  • Brain-Computer Interfaces*
  • Calcium / analysis*
  • Calcium Signaling*
  • Connectome / instrumentation
  • Connectome / methods*
  • Cytological Techniques / instrumentation
  • Electric Stimulation
  • Fluorescent Dyes
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / genetics
  • Image Processing, Computer-Assisted / methods*
  • Imaging, Three-Dimensional
  • Intravital Microscopy / instrumentation
  • Intravital Microscopy / methods*
  • Luminescent Proteins / analysis
  • Luminescent Proteins / genetics
  • Microscopy, Fluorescence / instrumentation
  • Microscopy, Fluorescence / methods
  • Models, Neurological
  • Motor Activity
  • Motor Cortex / cytology
  • Motor Cortex / physiology*
  • Nerve Net / physiology*
  • Nerve Net / ultrastructure
  • Neurons / chemistry
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Primates / anatomy & histology*
  • Primates / physiology
  • Single-Cell Analysis*
  • Transduction, Genetic
  • Wakefulness


  • Bacterial Proteins
  • Cyan Fluorescent Protein
  • Fluorescent Dyes
  • Luminescent Proteins
  • citrine protein, bacteria
  • Green Fluorescent Proteins
  • Calcium