Optogenetics in Brain Research: From a Strategy to Investigate Physiological Function to a Therapeutic Tool

Abstract

Dissecting the functional roles of neuronal circuits and their interaction is a crucial step in basic neuroscience and in all the biomedical field. Optogenetics is well-suited to this purpose since it allows us to study the functionality of neuronal networks on multiple scales in living organisms. This tool was recently used in a plethora of studies to investigate physiological neuronal circuit function in addition to dysfunctional or pathological conditions. Moreover, optogenetics is emerging as a crucial technique to develop new rehabilitative and therapeutic strategies for many neurodegenerative diseases in pre-clinical models. In this review, we discuss recent applications of optogenetics, starting from fundamental research to pre-clinical applications. Firstly, we described the fundamental components of optogenetics, from light-activated proteins to light delivery systems. Secondly, we showed its applications to study neuronal circuits in physiological or pathological conditions at the cortical and subcortical level, in vivo. Furthermore, the interesting findings achieved using optogenetics as a therapeutic and rehabilitative tool highlighted the potential of this technique for understanding and treating neurological diseases in pre-clinical models. Finally, we showed encouraging results recently obtained by applying optogenetics in human neuronal cells in-vitro.

Fully Implantable Low-Power High Frequency Range Optoelectronic Devices for Dual-Channel Modulation in the Brain

“…This results in the activation of Channel 1 for inhibition and the deactivation of Channel 2 for stimulation ( Figure S4d ). For the stimulation of neuronal populations, pulse signals must be delivered [ 24 ], and the following explains the procedures for stimulation. When the TX system sends a train of pulse signals, alternating electromagnetic (EM) fields or rectified AC signals trigger the reed switch ( Figure S4e ).…”

Cholinergic Deep Brain Stimulation for Memory and Cognitive Disorders

“…In a fuzzy-logic control system, time-varying spectral properties of the field potential are used as input by the digital signal processor [ 63 ]. Closed loop optogenetics DBS pre-clinical framework provides an opportunity for adding cell-type specific neuromodulation and circuit characterization [ 64 ]. Such future DBS application will provide a means to use activation of small specific spatial ensembles in the brain that cannot be activated with similar specificity otherwise, and to use this activation to counteract patterns of activity that are of neuropathological or psychiatric consequence.…”

Emerging Opportunities in Human Pluripotent Stem-Cells Based Assays to Explore the Diversity of Botulinum Neurotoxins as Future Therapeutics

“…As optogenetics allows selective targeting of individual cell types and activation or inhibition of their activity with a millisecond-scale time resolution, it offers a high degree of specificity and control over cellular network activity. This method requires the use of light-activated proteins called microbial opsins such as channelrhodopsin-2 (ChR2) for activation and halorhodopsin (NpHR) for silencing of cells [ 185 , 186 ]. ChR2 is a light-gated cation channel activated by blue light (470 nm) with high temporal precision.…”