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Optical deep-cortex exploration in behaving rhesus macaques

Nature Communications

Authors: Masanori Matsuzaki, Teppei Ebina
Publication: Nature Communications
Date: August 2, 2021
Link to article: https://www.nature.com/articles/s41467-021-24988-8


Non-human primates (NHPs) are important animal models for understanding higher brain functions relevant to complex human behaviors including cognition and motor control. In particular, rhesus macaques have been used for electrophysiological and anatomical studies. However, when electrodes, even multi-electrode arrays, are used for neuronal recording, it is difficult to simultaneously measure the activity of hundreds of neurons in local circuits. Furthermore, it is currently not technically possible to identify the location and morphology of multiple recorded neurons, identify the neuronal subtype, and confirm that the exact same neuron is recorded over a period of weeks to months. By contrast, calcium imaging via fluorescence microscopy is suitable for gathering longitudinal data on population activity in local circuits with the identification of single neurons. Calcium imaging is widely used in rodents, fish, and small invertebrates but its applications in behaving NHPs are limited1. This is because expression of genetically encoded calcium indicators (GECIs) is generally low (the reason for this is not clear) in the primate cortex and light scattering prevents imaging in deeper brain regions. Furthermore, chronic implantation of optical devices (cranial window or lens) in the large brain with minimal cortical damage is challenging and motion artifacts induced by arm movement, pulsation, and respiration need to be strictly suppressed. Despite these difficulties, two-photon imaging of GCaMP-expressing neurons in the motor cortex in head-fixed condition and one-photon calcium imaging of the motor cortex with a miniature microscope (miniscope) in a non-head-fixed condition during arm-movement tasks were established2,3 in a small NHP, the common marmoset. Two recently published papers overcame these challenges now also in the behaving macaque with a larger brain.

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