And Then There Was Light: Perspectives of Optogenetics for Deep Brain Stimulation and Neuromodulation

Abstract

Deep Brain Stimulation (DBS) has evolved into a well-accepted add-on treatment for patients with severe Parkinsons disease as well as for other chronic neurological conditions. The focal action of electrical stimulation can yield better responses and it exposes the patient to fewer side effects compared to pharmaceuticals distributed throughout the body toward the brain. On the other hand, the current practice of DBS is hampered by the relatively coarse level of neuromodulation achieved. Optogenetics, in contrast, offers the perspective of much more selective actions on the various physiological structures, provided that the stimulated cells are rendered sensitive to the action of light. Optogenetics has experienced tremendous progress since its first in vivo applications about 10 years ago. Recent advancements of viral vector technology for gene transfer substantially reduce vector-associated cytotoxicity and immune responses. This brings about the possibility to transfer this technology into the clinic as a possible alternative to DBS and neuromodulation. New paths could be opened toward a rich panel of clinical applications. Some technical issues still limit the long term use in humans but realistic perspectives quickly emerge. Despite a rapid accumulation of observations about patho-physiological mechanisms, it is still mostly serendipity and empiric adjustments that dictate clinical practice while more efficient logically designed interventions remain rather exceptional. Interestingly, it is also very much the neuro technology developed around optogenetics that offers the most promising tools to fill in the existing knowledge gaps about brain function in health and disease. The present review examines Parkinson's disease and refractory epilepsy as use cases for possible optogenetic stimulation therapies.

A Feasibility Study to Investigate Chemogenetic Modulation of the Locus Coeruleus by Means of Single Unit Activity

“…The serotype of the viral vector may be one of the primary reasons for the poor expression levels and aspecificity. The transduction efficiency of an AAV is determined by AAV entry in the target cell (Lai et al, 2002) which is controlled by the AAV capsid with its proteins on the surface that determine the binding specificity and entry of the virion to cells (Rabinowitz et al, 2002;Delbeke et al, 2017). In contrast to other groups who use the AAV2/9 and achieve high expression levels, in this study AAV2/7 was used which means that the genome of serotype 2 is encapsulated in a viral capsid formed by serotype 7 (Vazey and Aston-Jones, 2014;Cope et al, 2019).…”

Intrinsic Cell-type Selectivity and Inter-neuronal Connectivity Alteration by Transcranial Focused Ultrasound

“…Among these methods, optogenetics receives considerable attention for its capacity to selectively stimulate distinct cell-types (Packer et al, 2013;Rajasethupathy et al, 2016) with high spatial and temporal resolution (Boyden et al, 2005). However, optogenetics heavily relies on methods such as transgenic approaches, viral vector transfection or nanoparticle injection for deep brain application , which pose practical challenges for translation in human clinical utility (Delbeke et al, 2017). In contrast, non-invasive methods such as TMS and tCS are readily translated to clinical utility, but are challenged to achieve highly spatial focus and deep penetration.…”

Development of visual Neuroprostheses: trends and challenges

“…Optogenetic tools (Nagel et al, 2003) have the potential to bypass many of the limitations of electrical stimulation (Delbeke et al, 2017). This technique has been validated in blind animal models of Retinitis Pigmentosa (Sahel & Roska, 2013) and is moving towards human trials for retinal prosthesis (Sahel et al, 2015;Tung et al, 2016;Sengupta et al, 2016;Barrett et al, 2016).…”