Abstract
Motor capability recovery after ischemic stroke involves dynamic remodeling processes of neural connectomes in the nervous system. Various neuromodulatory strategies combining direct stimulating interventions with behavioral trainings for motor recovery after ischemic stroke have been developed. However, the effectiveness of these interventions varies widely due to unspecific activation or inhibition of undefined neuronal subtypes. Optogenetics is a functional and structural connection-based approach that can selectively activate or inhibit specific subtype neurons with a higher precision, and it has been widely applied to build up neuronal plasticities of the nervous system, which shows a great potential in restoring motor functions in stroke animal models. Here, we reviewed neurobiological mechanisms of enhanced brain plasticities underlying motor recovery through the optogenetic stimulation after ischemic stroke. Several brain sites and neural circuits that have been previously proven effective for motor function rehabilitation were identified, which would be helpful for a more schematic understanding of effective neuronal connectomes in the motor function recovery after ischemic stroke.
Highlights
Ischemic stroke, a leading cause of severe disabilities in the adult population, has an annual economic cost of approximately $34 billion all over the world [1]; it brings about a large number of familial and social burdens in lost productivity
One study comparing optogenetic versus electrical stimulation of dopamine terminals in the nucleus accumbens showed that electrical stimulation induces both local multisynaptic and indirect modulation of DA release, which are absent in optogenetically targeted stimulation [28]
To optimize the effect of stimulation-promoted recovery, we focused on the contralesional lateral cerebellar nucleus, a deep cerebellar nucleus that sends major excitatory output to multiple motor and sensory areas
Summary
A leading cause of severe disabilities in the adult population, has an annual economic cost of approximately $34 billion all over the world [1]; it brings about a large number of familial and social burdens in lost productivity. The brain functional networks undergo the reorganization and rewiring after a structural lesion from a stroke [3,4,5] These remodeling processes are often associated with the sprouting of spared axons that can innervate denervated target areas and the establishing of new circuits for the recovery of lost functions [6,7,8]. Optogenetics was used to excite neuronal activities selectively in the ipsilesional primary motor cortex (iM1) poststroke in transgenic mice expressing ChR2. The initially reestablished motor function can be extinguished by further optical silencing of newly sprouted fibers of intact CST neurons Such dual effects confirmed that specific axonal sprouting in contralateral corticospinal circuits is causally associated with recovery in these large-volume stroke models. Accompanied by optogenetics, the combined protocol could allow for an enhanced knowledge of the neural processes underlying the synergistic effects and potentially help to improve the effectiveness of rehabilitative therapy
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