Right vagus nerve stimulation promotes motor cortical plasticity

Figures

• 

  Fig. 1. Experimental design. (A) Rats were implanted with VNS cuff electrodes and were trained to perform a skilled reaching lever press task with their right forelimb. (B) Example traces illustrating lever deflection during hit (yellow line) versus miss (brown line) trials. Rats received a food reward pellet immediately upon successful completion of trials in which they fully depressed (deflection > 9.5 deg; Hit Threshold) and released (deflection returns to < 4.75 deg; Release/Reward Threshold) the lever within a 2-sec window (grey box). (C) Experimental timeline. After criterial performance was reached during Acquisition, rats were implanted with a VNS cuff electrode around the left or right cervical vagus nerve. Rats then continued to train until criterial performance was re-established. During the last 5 sessions of training, r-VNS, l-VNS, or sham simulation was paired with each correct lever press. The Sham group included animals with left (n = 3) and right (n = 4) implants. M1 mapping occurred ca. 24 h after the final training-paired treatment session.

• 

  Fig. 2. Both l-VNS and r-VNS induce task-relevant M1 plasticity. (A) M1 motor maps from representative sham, left VNS (Left), and right VNS (Right) animals. PFL: proximal forelimb, DFL: distal forelimb, Ant. Body: anterior body representations (jaw, vibrissa, and neck), Post. Body: posterior body representations (trunk, hindlimb, and tail), NR: no response. (B-C) Rats in l-VNS and r-VNS treatment groups exhibited a significant increase in the size of the PFL representation in M1 (B) and a decrease in the size of the DFL representation (C) compared to sham treated rats. **p < 0.01, ***p < 0.001, ****p < 0.0001, Bonferroni corrected t-tests. (D) Overall map size was similar across treatment groups. Black circles in B-D denote data from individual animals; Error bars denote SEM.

• 

  Fig. 3. VNS did not alter task execution. (A–F) No significant differences were observed across treatment groups in percent correct performance (A), average trial duration (C), or average lever pressing speed (E) during Pre-Treatment (-) or Treatment (+) periods, and no treatment produced a significant change in percent correct (A, B), trial duration (C, D), or lever pressing speed (E, F). Black circles in B, D, and F represent data from individual animals; Error bars represent SEM.

• 

  Fig. 4. r-VNS treatment was associated with a decrease in task engagement. (A) A significant decrease in number of trials performed was observed between the Pre-Treatment (-) and Treatment (+) periods in the r-VNS group, but not in the sham or l-VNS groups; *p < 0.05, paired t-test. (B) Across treatment groups, there was no significant difference in the treatment-dependent change in trials performed, despite the reduction seen within the r-VNS group. (C) Average pellets rewarded across session time during Treatment (solid lines) and Pre-Treatment (dashed lines) periods. r-VNS Treatment was associated with a significant reduction in pellets received across all time bins, compared to Pre-Treatment; *all FDR q < 0.05, time-resolved contrast analysis. Shading denotes SEM. (D) Across all rats, the relationship between average weight and average number of pellets rewarded per session trended toward significance (Pearson’s linear correlation); dots represent average data across all 10 Pre-Treatment and Treatment sessions for each rat in the study. (E) Variations in weight around each animals’ average are anticorrelated with variation in pellets received, suggesting task engagement is sensitive…