title: Optogenetic-guided cortical plasticity after nerve injury.
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.
authors.affiliation: FM Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: John E
authors.initials: JE
authors.lastname: Downey
authors.forename: Amnon
authors.initials: A
authors.lastname: Bar-Shir
authors.forename: Assaf A
authors.initials: AA
authors.lastname: Gilad
authors.forename: Piotr
authors.initials: P
authors.lastname: Walczak
authors.forename: Heechul
authors.initials: H
authors.lastname: Kim
authors.forename: Suresh E
authors.initials: SE
authors.lastname: Joel
authors.forename: James J
authors.initials: JJ
authors.lastname: Pekar
authors.forename: Nitish V
authors.initials: NV
authors.lastname: Thakor
authors.forename: Galit
authors.initials: G
authors.lastname: Pelled
mesh_terms: D000818:Animals; D001931:Brain Mapping / Q000379:methods; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D025602:Halorhodopsins / Q000235:genetics; D007395:Interneurons; D009473:Neuronal Plasticity; D059348:Peripheral Nerve Injuries; D015202:Protein Engineering; D051381:Rats; D012683:Sensory Deprivation; D013003:Somatosensory Cortex / Q000473:pathology / Q000503:physiopathology; D020196:Trauma, Nervous System / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology
chemical_list: D025602:Halorhodopsins