Fig. 1

Specific optogenetic stimulation of the intact corticospinal tract originating from the contralesional hemisphere results in robust recovery of lost forelimb function after stroke. a Timeline for the four different treatment groups. b Schematic diagram of viral vector injections into the contralesional motor cortex (AAV2.1-Ef1a-DIO-hChR2(t159C)-mCherry) and the corresponding cervical hemi-spinal cord (AAV2.9-CamKII0.4.Cre.SV40) to specifically express Channelrhodopsin-2 (ChR2) in the intact corticospinal neurons. c Success rates in the single pellet grasping task relative to baseline (100%; intact, trained) 2 days to 5 weeks after a large, unilateral photothrombotic stroke to the sensorimotor cortex of the preferred paw. The “OptoStim/Training” and “OptoStim” groups showed significant improvement of skilled forelimb function compared to the other groups. Both stimulation groups (“OptoStim” and “OptoStim/Training” group) also performed significantly better in novel tasks to assess recovery of forelimb function such as the narrow beam task (d) and the horizontal ladder crossing task (e) tested at 5 weeks after stroke. Shown are average success rates of three consecutive trials. f Representative images of mCherry-positive cells (a) in the sensorimotor cortex in comparison to Nissl-positive cells (b) (a, b: scale bars = 50 μm) as well as quantification of mCherry-positive cells in percentage of Nissl-positive cells in layer 5 of pre- (M2), primary motor cortex (M1), and primary sensory cortex (S1) for both “stimulation” groups. Data are presented as means ± s.e.m.; statistical evaluation was carried out with two-way (for c) and one-way (for d, e) ANOVA repeated measure followed by Bonferroni post hoc, and with paired t-test, two-tailed for F; asterisks indicate significances: *p < 0.05, **p < 0.01, and ***p < 0.001