Optogenetic stimulation: Understanding memory and treating deficits

Abstract

Technology allowing genetically targeted cells to be modulated by light has revolutionized neuroscience in the past decade, and given rise to the field of optogenetic stimulation. For this, non-native, light activated proteins (e.g., channelrhodopsin) are expressed in a specific cell phenotype (e.g., glutamatergic neurons) in a subset of central nervous system nuclei, and short pulses of light of a narrow wavelength (e.g., blue, 473 nm) are used to modulate cell activity. Cell activity can be increased or decreased depending on which light activated protein is used. We review how the greater precision provided by optogenetics has transformed the study of neural circuits, in terms of cognition and behavior, with a focus on learning and memory. We also explain how optogenetic modulation is facilitating a better understanding of the mechanistic underpinnings of some neurological and psychiatric conditions. Based on this research, we suggest that optogenetics may provide tools to improve memory in neurological conditions, particularly diencephalic amnesia and Alzheimer's disease.

LSO:Ce Inorganic Scintillators are Biocompatible with Neuronal and Circuit Function

“…Over the past decade, the field of optogenetics has expanded our knowledge about the role of individual neuronal cells and specific brain circuits in behavior and disease states (Gradinaru et al, 2009; Yizhar et al, 2011; Lim et al, 2013; Gunaydin et al, 2014; Emiliani et al, 2015; Fenno et al, 2015; Rost et al, 2017; Selimbeyoglu et al, 2017; Barnett et al, 2018). Optogenetics relies on the expression of exogenous light activated ion channels, including the blue light-activated channelrhodopsin-2 (ChR2), that causes depolarization, or the orange-light activated halorhodopsin, which causes hyperpolarization, of the membrane potential of brain cells of interest.…”

The Memory-Modifying Potential of Optogenetics and the Need for Neuroethics

“…Another disease awaiting the approval of initial clinical trials involving the application of optogenetic therapy and for which existing methods of treatment show limited effectiveness is urinary bladder syndrome [5]. Furthermore, many optogenetic studies conducted on animal models, such as rodents or nonhuman primates [6], were designed with the explicit goal of developing better targeted brain stimulation treatments for various psychiatric and neurological disorders in humans [7][8][9][10][11][12][13][14]. These attempts, along with rapid advancements in the field, demonstrate that optogenetics is already progressing towards clinical application.…”

“…This optogenetic procedure also has the unique advantage of not relying on human-derived factors that might moderate the rate of success in implanting false memories. For instance, in a classic study that used the "Lost in the Mall" technique, 7 implantation of false memories of being lost in a shopping mall in childhood [31] was successful in onlỹ 25% of participants (or even less, see [32]); further studies showed that this success rate might be greatly dependent on the convincingness of the story, the characteristics of those subjected to this procedure (e.g., age and level of suggestibility), and the characteristics of those conveying the story (such as age advantage and family relationship between the implanter of the false memory and the individual who had the memory implanted) (e.g., [33]).…”

“…Last but not least, optogenetic intervention has been recently tested as a potential treatment for various models of neurological disorders tested in animals. The latest evidence indicates that optogenetics, similar to DBS [63], shows potential for improving memory impairments observed in neurological conditions such as diencephalic amnesia and Alzheimer's disease through stimulating small thalamic nuclei [7]. Optogenetics has also contributed significantly to an improved understanding of the dysfunctional neural circuits underlying PTSD [64] and Parkinson's disease [65], inspiring novel circuit-inspired applications of DBS (ibidem).…”

Raman Scattering: From Structural Biology to Medical Applications

“…Optogenetics is a powerful technique that was primarily viewed as a tool for studying neuroscience and brain mapping [11,12]. Nowadays, it has a broad range of applications and it is also used to recover neuronal pathways that are impaired as a result of neurodegenerative diseases, traumas, or stroke [13], studying nociceptive function of peripheral nervous system important for pain treatment [14], engineering retinal implants [15], investigation of cardiac tissue [16], developmental biology [17], and controlling cellular processes with light [18].…”