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.

Highlights

  • Optogenetics is a non-invasive technique largely used in neuroscience to study brain circuit functions on multiple scales by allowing neuronal activity manipulation with high temporal and spatial resolution

  • Optogenetic treatments are still limited to pre-clinical models, they are proving to be a promising strategy

  • By using a state-dependent closedindependently, suggesting a hierarchal organization—striatal direct pathway facilitates actions and loop optogenetic interference they demonstrated that action sequencesthe in aswitch complex controls sequencestimulation start/stop, and while indirect pathway inhibits actions and mediates to task are controlled independently, suggesting a hierarchal organization—striatal direct pathway the following sequence. These results provide important information in order to elucidate how cortico-basal ganglia circuits work in coordination processes [88] and suggest new targets for the treatment of Parkinson’s disease in which the action sequences organization is highly compromised

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Summary

Introduction

Optogenetics is a non-invasive technique largely used in neuroscience to study brain circuit functions on multiple scales by allowing neuronal activity manipulation with high temporal and spatial resolution. The high spatial resolution of this technique makes it one of the most precise low-invasive brain stimulation strategy, highly suitable for the development of targeted therapeutic protocols for neurodegenerative diseases and injuries, such as Parkinson, depression, stroke, and multiple sclerosis [3,4]. Optogenetic treatments are still limited to pre-clinical models, they are proving to be a promising strategy. We reported recent applications to cortical and subcortical neuronal circuits in vivo, which allowed us to identify physiological mechanisms and new plausible targets for light-based therapies. We introduced recent studies that exploited optogenetics as a rehabilitation strategy, showing the potential of this technique to replace drug treatments in pre-clinical models

Opsins
Light Sources and Light Delivery Systems
Optogenetics to Dissect Disease Neural Circuitry
Light as Rehabilitative Strategy in Pre-Clinical Models
Parkinson’s Disease
Stroke
Other Therapeutic Applications
The Future of Optogenetics
Findings
Methods

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