Optogenetically-inspired neuromodulation: Translating basic discoveries into therapeutic strategies

Caitlin Murphy, Bridget Matikainen-Ankney, Yu Hsuan Chang, Bryan Copits, Meaghan C. Creed

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Optogenetic tools allow for the selective activation, inhibition or modulation of genetically-defined neural circuits with incredible temporal precision. Over the past decade, application of these tools in preclinical models of psychiatric disease has advanced our understanding the neural circuit basis of maladaptive behaviors in these disorders. Despite their power as an investigational tool, optogenetics cannot yet be applied in the clinical for the treatment of neurological and psychiatric disorders. To date, deep brain stimulation (DBS) is the only clinical treatment that can be used to achieve circuit-specific neuromodulation in the context of psychiatric. Despite its increasing clinical indications, the mechanisms underlying the therapeutic effects of DBS for psychiatric disorders are poorly understood, which makes optimization difficult. We discuss the variety of optogenetic tools available for preclinical research, and how these tools have been leveraged to reverse-engineer the mechanisms underlying DBS for movement and compulsive disorders. We review studies that have used optogenetics to induce plasticity within defined basal ganglia circuits, to alter neural circuit function and evaluate the corresponding effects on motor and compulsive behaviors. While not immediately applicable to patient populations, the translational power of optogenetics is in inspiring novel DBS protocols by providing a rationale for targeting defined neural circuits to ameliorate specific behavioral symptoms, and by establishing optimal stimulation paradigms that could selectively compensate for pathological synaptic plasticity within these defined neural circuits.

Original languageEnglish
Title of host publicationEmerging Horizons in Neuromodulation
Subtitle of host publicationNew Frontiers in Brain and Spine Stimulation
EditorsElena Moro, Mircea Polosan, Clement Hamani
PublisherAcademic Press Inc.
Pages187-219
Number of pages33
ISBN (Print)9780128222980
DOIs
StatePublished - Jan 2021

Publication series

NameInternational Review of Neurobiology
Volume159
ISSN (Print)0074-7742
ISSN (Electronic)2162-5514

Keywords

  • Addiction
  • Archaerhodopsin
  • Basal ganglia
  • Channelrhodopsin
  • Deep brain stimulation
  • Neural circuit
  • Obsessive compulsive disorder
  • Synaptic plasticity

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