Figure 6.

Awake chemo-fMRI functional network reorganization with increasing excitability of the dorsal hippocampus (DH) in rats: Subdividing the brain into 96 clusters identifies whole-brain and dorsal hippocampus connectivity changes with increased DH excitability. (A) Experimental timeline: Rats (n = 7) were first injected with AAV9-SYN-PSAM-L141F-Y115F-5HT3HC-GFP virus into the bilateral dorsal hippocampus (∼9 weeks before SNI surgery). Two weeks later, they received head-posts (∼7 weeks) and then underwent a 2-week training period to enable awake resting-state fMRI; 1 to 2 days before SNI injury, baseline tactile thresholds were assessed for left and right hind paws (BL VF). Spared nerve injury surgery was then performed unilaterally. Four or 5 days after surgery, tactile thresholds (T0) were assessed, and the rats scanned for resting-state fMRI (rsfMRI); immediately afterwards, rats received either saline or PSEM^89s injections (i.p.), retested for tactile thresholds, and again underwent awake rsfMRI (2 consecutive scans). Two hours later, rats that had received PSEM^89s were injected with saline, and vice versa, and tactile thresholds and rsfMRI were assessed one more time. (B–C), Dorsal and lateral views of change in network connectivity with increased DH excitability, comparing PSEM^89s with the saline injection conditions. Change in connectivity across all nodes is shown in gray; increased and decreased connectivity for the 4 DH seeds (green) are shown in red and blue, respectively. (D) Histogram of the significant changes in the average correlation coefficient for PSEM^89s in contrast to saline: Contrasts were performed combining scan 1 and 2 data, using permutation testing, P < 0.05 (see Table S2 for statistical details, available at http://links.lww.com/PAIN/B350). A, anterior; D, dorsal; L, left; P, posterior; R, right; SNI, spared nerve injury; V, ventral.