Fig. 3: Receptor-specific focal modulation of cortical circuits by AU-FUS.

a Experimental setup for in vivo drug delivery. The recording probe was inserted in vM1 or V1 and the FUS transducer was positioned above vS1. Contralateral whiskers (eye) were mechanically deflected (visually stimulated) at 0.3 Hz. UC-carriers were IV-injected through the tail vein. vM1 and V1 recordings were performed on separate cohorts. b Representative peri-stimulus histograms (PSTHs, top, bin size 2 ms) and wEPs (bottom) upon focal aggregation of muscimol-loaded UC-carriers and uncaging of muscimol from one experiment. Following a baseline recording (shaded area), the animal was injected with muscimol-loaded UC-carriers and FUS was turned on. wEPs showed 62.62% inhibition. PSTHs and wEPs recovered completely ~75 min post FUS. The wEPs and PSTHs were averaged over 2 min windows. c Time course of normalized wEPs in vM1. Muscimol-loaded UC-carriers with AU-FUS [black line, n = 24 (6 rats × 4 recording sites)], vehicle-loaded UC-carriers with AU-FUS [blue line, n = 24 (6 rats × 4 recording sites)], AU-FUS without UC-carrier injection [green line, n = 36 (9 experiments × 4 recording sites, from 5 rats)], muscimol-loaded UC-carrier injection without AU-FUS [brown line, n = 20 (5 rats × 4 recording sites)], systemic injection of free muscimol (250 ng) with AU-FUS [orange line, n = 20 (5 rats × 4 recording sites)], systemic injection of free muscimol (250 ng) and vehicle-loaded UC-carriers with AU-FUS [pink line, n = 20 (5 rats × 4 recording sites)]. d Post-treatment (30 min average) vs. baseline (10 min average) wEPs. Statistical comparison (Wilcoxon matched-pairs-signed rank test): baseline vs. treatment; Black (muscimol-loaded UC-carriers + AU-FUS), ****p < 0.0001; Blue (vehicle-loaded UC-carriers + AU-FUS), p = 0.3902; Green (AU-FUS only), p = 0.2371; Brown (muscimol-loaded UC-carriers only), p = 0.8695; Orange (250 ng free muscimol + AU-FUS), p = 0.1737; Pink (vehicle-loaded UC-carriers + 250 ng free muscimol + AU-FUS), p = 0.2611. All data is mean ± s.e.m. e Locally uncaged muscimol does not spread to neighboring cortical areas. Normalized eLFP responses (VEP, purple line) in neighboring V1, as compared to responses (wEP, black line) in vM1. f VEPs from V1. Statistical comparison (Wilcoxon matched-pairs-signed rank test): baseline (10 min average) vs. treatment (30 min average), (p = 0.5199, n = 16 (4 rats × 4 recording sites). All data is mean ± s.e.m.