Optogenetic-guided cortical plasticity after nerve injury

Nan Li, John E. Downey, Amnon Bar-Shir, Assaf A. Gilad, Piotr Walczak, Heechul Kim, Suresh E. Joel, James J Pekar, Nitish V Thakor, Galit Pelled

Research output: Contribution to journalArticle

Abstract

Peripheral nerve injury causes sensory dysfunctions that are thought to be attributable to changes in neuronal activity occurring in somatosensory cortices both contralateral and ipsilateral to the injury. Recent studies suggest that distorted functional response observed in deprived primary somatosensory cortex (S1) may be the result of an increase in inhibitory interneuron activity and is mediated by the transcallosal pathway. The goal of this study was to develop a strategy to manipulate and control the transcallosal activity to facilitate appropriate plasticity by guiding the cortical reorganization in a rat model of sensory deprivation. Since transcallosal fibers originate mainly from excitatory pyramidal neurons somata situated in laminae III and V, the excitatory neurons in rat S1 were engineered to express halorhodopsin, a light-sensitive chloride pump that triggers neuronal hyperpolarization. Results from electrophysiology, optical imaging, and functional MRI measurements are concordant with that within the deprived S1, activity in response to intact forepaw electrical stimulation was significantly increased by concurrent illumination of halorhodopsin over the healthy S1. Optogenetic manipulations effectively decreased the adverse inhibition of deprived cortex and revealed the major contribution of the transcallosal projections, showing interhemispheric neuroplasticity and thus, setting a foundation to develop improved rehabilitation strategies to restore cortical functions.

Original languageEnglish (US)
Pages (from-to)8838-8843
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number21
DOIs
StatePublished - May 24 2011

Fingerprint

Halorhodopsins
Optogenetics
Somatosensory Cortex
Sensory Deprivation
Peripheral Nerve Injuries
Neuronal Plasticity
Pyramidal Cells
Electrophysiology
Optical Imaging
Wounds and Injuries
Carisoprodol
Interneurons
Lighting
Electric Stimulation
Chlorides
Rehabilitation
Magnetic Resonance Imaging
Neurons
Light

Keywords

  • Amputation
  • Recovery

ASJC Scopus subject areas

  • General

Cite this

Optogenetic-guided cortical plasticity after nerve injury. / Li, Nan; Downey, John E.; Bar-Shir, Amnon; Gilad, Assaf A.; Walczak, Piotr; Kim, Heechul; Joel, Suresh E.; Pekar, James J; Thakor, Nitish V; Pelled, Galit.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 21, 24.05.2011, p. 8838-8843.

Research output: Contribution to journalArticle

Li, Nan ; Downey, John E. ; Bar-Shir, Amnon ; Gilad, Assaf A. ; Walczak, Piotr ; Kim, Heechul ; Joel, Suresh E. ; Pekar, James J ; Thakor, Nitish V ; Pelled, Galit. / Optogenetic-guided cortical plasticity after nerve injury. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 21. pp. 8838-8843.
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