title: The need for calcium imaging in nonhuman primates: New motor neuroscience and brain-machine interfaces.
abstract: 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.
authors: Neurosciences Program, Stanford University, Stanford, CA 94305, United States.
authors: Daniel J
authors: DJ
authors: O'Shea
authors: Neurosciences Program, Stanford University, Stanford, CA 94305, United States.
authors: Eric
authors: E
authors: Trautmann
authors: Department of Electrical Engineering, Stanford University, Stanford, CA 94305, United States.
authors: Chandramouli
authors: C
authors: Chandrasekaran
authors: Neurosciences Program, Stanford University, Stanford, CA 94305, United States.
authors: Sergey
authors: S
authors: Stavisky
authors: Department of Electrical Engineering, Stanford University, Stanford, CA 94305, United States.
authors: Jonathan C
authors: JC
authors: Kao
authors: Department of Electrical Engineering, Stanford University, Stanford, CA 94305, United States; Gatsby Computational Neuroscience Unit, University College London, London W1T 4JG, United Kingdom.
authors: Maneesh
authors: M
authors: Sahani
authors: Department of Electrical Engineering, Stanford University, Stanford, CA 94305, United States; Department of Neurosurgery, Palo Alto Medical Foundation, Palo Alto, CA 94301, United States.
authors: Stephen
authors: S
authors: Ryu
authors: Department of Bioengineering, Stanford University, Stanford, CA 94305, United States; Department of Psychiatry and Behavioral Science, Stanford University, Stanford, CA 94305, United States; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, United States.
authors: Karl
authors: K
authors: Deisseroth
authors: Department of Electrical Engineering, Stanford University, Stanford, CA 94305, United States; Department of Bioengineering, Stanford University, Stanford, CA 94305, United States; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, United States; Deparment of Neurobiology, Stanford University, Stanford, CA 94305, United States. Electronic address: shenoy@stanford.edu.
authors: Krishna V
authors: KV
authors: Shenoy
mesh_terms: D000465:Algorithms; D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics; D001522:Behavior, Animal; D062207:Brain-Computer Interfaces; D002118:Calcium / Q000032:analysis*; D020013:Calcium Signaling; D063132:Connectome / Q000295:instrumentation / Q000379:methods*; D003584:Cytological Techniques / Q000295:instrumentation; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional; D000069416:Intravital Microscopy / Q000295:instrumentation / Q000379:methods*; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008856:Microscopy, Fluorescence / Q000295:instrumentation / Q000379:methods; D008959:Models, Neurological; D009043:Motor Activity; D009044:Motor Cortex / Q000166:cytology / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D011323:Primates / Q000033:anatomy & histology* / Q000502:physiology; D059010:Single-Cell Analysis; D014161:Transduction, Genetic; D014851:Wakefulness
chemical_list: D001426:Bacterial Proteins; C485182:Cyan Fluorescent Protein; D005456:Fluorescent Dyes; D008164:Luminescent Proteins; C434479:citrine protein, bacteria; D049452:Green Fluorescent Proteins; D002118:Calcium
keywords: Brain-machine interfaces; Calcium imaging; Macaque; Motor cortex; Motor system; Neural circuits; Neural computation; Nonhuman primates; Population dynamics; Prosthetics