Genetically-targeted control of the spinal cord and peripheral nervous system

Abstract

Genetically-targeted neuromodulation, such as opto- or chemogenetics, is important for cell-type specific neuromodulation for different applications. Modulating peripheral nerves is a daunting task due to the wide variety of constraints in the periphery, such as size, location, and relative distance to other nerves. This has resulted in many researchers developing innovative solutions to modulate peripheral nerves, including different types of light-emitting devices for optogenetics, different ligands and designer drugs (DREADDs) for chemogenetics, and use of nanotechnology. Although the spinal cord is part of the central nervous system, it is often a site of stimulation for the modulating function in the periphery and the anatomy of the spinal cord has many of the same obstacles for modulation as peripheral nerves. This review summarizes current efforts in genetically-targeted neuromodulation of the spinal cord and peripheral nerves. This review is grouped by applications, going through major areas in which advancements for peripheral neuromodulation have been made. We focus on in vivo research in rodents but also briefly discuss current work in nonhuman primates (NHPs). Some of the major obstacles to clinical translation, such as long-term adeno-associated virus (AAV) safety, are discussed and some noninvasive, nonspecific technologies for peripheral neuromodulation are briefly mentioned.

Keywords

chemogenetics / neuromodulation / optogenetics / peripheral nervous system / spinal cord

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