Multi-area recordings and optogenetics in the awake, behaving marmoset

Abstract

The common marmoset has emerged as a key model in neuroscience. Marmosets are small in size, show great potential for genetic modification and exhibit complex behaviors. Thus, it is necessary to develop technology that enables monitoring and manipulation of the underlying neural circuits. Here, we describe a novel approach to record and optogenetically manipulate neural activity in awake, behaving marmosets. Our design utilizes a light-weight, 3D printed titanium chamber that can house several high-density silicon probes for semi-chronic recordings, while enabling simultaneous optogenetic stimulation. We demonstrate the application of our method in male marmosets by recording multi- and single-unit data from areas V1 and V6 with 192 channels simultaneously, and show that optogenetic activation of excitatory neurons in area V6 can influence behavior in a detection task. This method may enable future studies to investigate the neural basis of perception and behavior in the marmoset.

The neurobiology of vocal communication in marmosets

“…A recurring theme throughout has been an emphasis on vocal communication in natural behavioral contexts, as it is in these settings that the neural processes that evolution selected to overcome the idiosyncratic challenges of communication will be most apparent 181 . Answers to these challenges are becoming increasingly attainable with the recent developments in gene editing, allowing for genetically expressed calcium indicators, 6 and high‐density silicon probe recordings 192,193 to record large populations of neurons from the brain. While these cutting‐edge neural recording approaches are critical, elucidating the neural basis of natural behavior hinges on techniques being developed to be used in freely moving experiments 192–194 combined with novel behavioral paradigms, 209,228 which exploit the wide range of natural behaviors in marmosets 37,101,194,229 .…”

“…181 Answers to these challenges are becoming increasingly attainable with the recent developments in gene editing, allowing for genetically expressed calcium indicators, 6 and high-density silicon probe recordings 192,193 to record large populations of neurons from the brain. While these cutting-edge neural recording approaches are critical, elucidating the neural basis of natural behavior hinges on techniques being developed to be used in freely moving experiments [192][193][194] combined with novel behavioral paradigms, 209,228 which exploit the wide range of natural behaviors in marmosets. 37,101,194,229 This is particularly important as various behaviors can cause widespread activation across the brain and strongly predict activity across various regions, 230,231 suggesting that vocal communication should be studied in concert with other natural behaviors.…”

“…Many systems for neuronal recording, such as two‐photon imaging 188 and various methods of neurophysiology, 103,189 that traditionally required head‐fixed animals are being adapted for freely moving paradigms. Tethered miniaturized microscopes, for example, can be used to record calcium transients during natural behavior, 190 while wireless neural recording technologies can be used to record spiking activity with silicon probes and other electrodes 191,192 . These methods have meant a significant improvement in the breadth of behaviors whose underlying neurobiology can be studied in naturalistic contexts, 193,194 but their use in marmosets comes with important considerations.…”

“…Tethered miniaturized microscopes, for example, can be used to record calcium transients during natural behavior, 190 while wireless neural recording technologies can be used to record spiking activity with silicon probes and other electrodes. 191,192 These methods have meant a significant improvement in the breadth of behaviors whose underlying neurobiology can be studied in naturalistic contexts, 193,194 but their use in marmosets comes with important considerations. Because of the marmosets relatively small body size, wireless equipment must be lightweight to not impede the animals' movements, 193 while at the same time, it must be designed to withstand the rigors of a 3D arboreal lifestyle.…”

Construction of a Flexible Optogenetic Device for Multisite and Multiregional Optical Stimulation Through Flexible µ‐LED Displays on the Cerebral Cortex

“…[5] To better understand the underlying causes and gain effective treatment approaches of these neurological disorders, [6,7] optogenetics technology that combines optics and genetics to modulate specific neurons in living organisms has made a significant impact on the study of neurological and psychiatric conditions. [8][9][10][11] Despite the development of some advanced optogenetic devices, such as silicon-based optoelectronic probes, [12,13] pipette-integrated microelectrodes, [14,15] and glass microneedle arrays, [16,17] their rigid and brittle nature is mechanically mismatched with the soft and curved biological tissue, [18][19][20] urging the need for more advanced electronic devices capable of conformal integration and stable interfacing with brain tissue.…”