Fig. 4: Closed-loop VNS increases putative central synaptic connectivity of injured networks without altering peripheral reinnervation.
From: Enhancing plasticity in central networks improves motor and sensory recovery after nerve damage
a Representative images depicting muscle fibers from the denervated digit flexors. Muscle fibers were visualized using non-specific background fluorescence. Scale bar is 100 µm. b No differences were observed in fiber area or other metrics of muscle morphology (Rehab, n = 5; CL-VNS, n = 8; Delayed VNS, n = 7; uninjured, n = 6; Kruskal–Wallis test, see Supplementary Fig. 14). Histology on nerve and muscle sections was collected from subjects at week 13. c Representative images of nerves harvested from subjects at the conclusion of rehabilitation illustrating nerve morphology proximal and distal to the injury site in both a Rehab and CL-VNS subject. The distal sections show some reinnervation, but substantially impaired nerve architecture in subjects from all groups. Scale bar is 10 µm. d Nerve injury substantially disrupts nerve architecture distal to the injury site in the median nerve (Rehab, n = 3; CL-VNS, n = 3; Delayed VNS, n = 3, Kruskal–Wallis test). However, no differences in myelin area or other measures of nerve health were observed across groups (see Supplementary Figs. 10–13), indicating that VNS does not influence peripheral reinnervation. e Pseudorabies virus (PRV) tracing of putative central synaptic connectivity reveals that CL-VNS delivered with rehabilitation (n = 5) significantly increased the number of neurons in layer 5 (LV) motor cortex synaptically coupled to forelimb digit flexors compared to Rehab (n = 5), consistent with the expansion of digit flexion movement representations in the cortical maps. Same group sizes in e–g. f No differences were observed in the connectivity of the spared extensor networks. g CL-VNS significantly reduced the percentage of neurons displaying connectivity to both digit flexion and extensor muscles. Circles depict individual subjects in b, d–g. Error bars indicate S.E.M. All comparisons in e–g represent unpaired t-tests, ***p < 0.001, **p < 0.01, *p < 0.05. Source data are provided as a Source Data file.
