Overview on Research and Clinical Applications of Optogenetics

Abstract

Optogenetics is a method that uses light to control cells in living tissue, typically neurons, that have been modified to express light-sensitive ion channels and pumps. The approach facilitates neuromodulation in brain preparations and freely moving animals with unmatched spatial and temporal resolution. This optogenetics overview describes the vast array of light-sensitive proteins available and the methods used to deliver them to tissue and modulate them with light. How these methods have so far enhanced our knowledge of fundamental neuroscience and psychiatric disease will be discussed as well as how they may contribute to drug discovery in the future. Finally, the potential rewards and risks of therapeutic gene transfer of optogenetic proteins in humans will be considered. © 2016 by John Wiley & Sons, Inc.

Behavioral Manipulation by Optogenetics in the Nonhuman Primate

“…Beyond that, optogenetics may provide possible alternative to deep brain stimulation (DBS) to treat Parkinson’s disease, depression, and so on, with the advantages of more specific stimulation and the potential to reduce the side effects (e.g., mood change and suicide attempt) caused by DBS, which were thought to be associated with the imprecise targeting and the stimulation parameters (Voon and others 2013). Moreover, by inhibiting specific brain regions or sensory neurons, optogenetics can be effective in interrupting seizure generation and drug addiction, as well as treating chronic pain (Towne and Thompson 2016). In addition, optogenetics can be used as a neuromodulator in neuroprosthetic applications to compensate for sensory loss due to stroke, spinal cord injury or other neurodegenerative diseases, and to enable the brain to directly control external devices.…”

Optogenetics: Applications in neurobiology

“…When ChR2 is expressed in neurons, its activation by blue light opens the channel, thereby depolarizing the membrane, which allows sodium and potassium ions to flow down their electrochemical gradient into the cell. This blue light-activated cation channel allows millisecond-precision excitation of neurons Towne and Thompson, 2016). Conversely, there is a microbial opsin that has been optimized to push the membrane voltage in the opposite direction and thus inhibit neural activity (Han et al, 2011;Stefaniket et al, 2013).…”

“…Adjacent cells that do not express the Cre-recombinase are infected by the virus but do not express the opsin. By combining this with projection-based strategies, highly specific circuit targeting can be achieved (Towne and Thompson, 2016).…”

In vivo methods for acute modulation of gene expression in the central nervous system

“…In particular, in recent years, basic research has benefited from new tools for gene editing ( e.g. , CRISPR-Cas9 technology; Ahmad et al, 2018) and neuronal-activity modulation (optogenetics and chemogenetics; Dobrzanski and Kossut, 2017; Towne and Thompson, 2016), which both need to be coupled to a nucleic acid delivery system. For translational research, a fast-growing field of study focuses on the possibility of treating CNS disorders by manipulating gene expression (gene therapy) rather than by classical pharmacology, which has proven highly ineffective in the last 10 years (Gribkoff and Kaczmarek, 2017).…”