Fig. 4: Unique electrophysiologic signatures of AAL-mediated regional ketamine uncaging. | Nature Nanotechnology

Fig. 4: Unique electrophysiologic signatures of AAL-mediated regional ketamine uncaging.

From: Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation

Fig. 4

a, Schematic (left) and timeline (right) of 45 min recording from fully awake rats undergoing acute restraint stress. Following 5 min baseline, intravenous. infusion administered t = 5–10 min and FUS (250 kHz; 1.1 MPa estimated in situ peak negative pressure; 50 ms/5 Hz PRF/2.5 min) applied t = 7.5–10 min (https://BioRender.com/u2nnlio and https://BioRender.com/byb05hr). b, Spectrograms depicting electrophysiological response to saline with ultrasound and free KetHCl (0.75 mg kg−1; repeated from dose–response evaluation; Extended Data Fig. 5), SonoKet (0.75 mg kg−1) without ultrasound, and SonoKet with ultrasound applied to and recording from mPFC (top row; n = 4–5) or RsC (bottom row; n = 5–6). Power spectral density percent changes from the baseline (0–5 min) were calculated. c, Power spectral density percent change from baseline versus frequency for time of sonication (7.5–10 min), immediately after treatment (10–25 min) and in a delayed period (25–45 min). d, Power spectral density percent change from baseline area under the curve for each time period and spectral band: theta (4–8 Hz), alpha (8–15 Hz), beta (15–25 Hz) and gamma (25–55 Hz). mPFC post-treatment, gamma: Sal + FUS versus SonoKet + FUS (P = 0.0156); SonoKet versus SonoKet + FUS (P = 0.0179). RsC treatment, theta: Sal + FUS versus SonoKet + FUS (P = 0.0081); KetHCl versus SonoKet + FUS (P = 0.0085). Alpha: Sal + FUS versus SonoKet + FUS (P = 0.0183); KetHCl versus SonoKet + FUS (P = 0.0076); SonoKet versus SonoKet + FUS (P = 0.0376). Beta: Sal + FUS versus SonoKet + FUS (P = 0.0136); KetHCl versus SonoKet + FUS (P = 0.0028); SonoKet versus SonoKet + FUS (P = 0.0047). Gamma: Sal + FUS versus SonoKet + FUS (P = 0.0231). RsC post-treatment, beta: KetHCl versus SonoKet + FUS (P = 0.0271); SonoKet versus SonoKet + FUS (P = 0.0365). Gamma: KetHCl versus SonoKet + FUS (P = 0.0431); SonoKet versus SonoKet + FUS (P = 0.0177). RsC 25–45 min, gamma: KetHCl versus SonoKet + FUS (P = 0.0228); SonoKet versus SonoKet + FUS (P = 0.0487). Data presented as box plots show minima, maxima, interquartile range (box bounds) and median (black line). One-way, two-sided, ANOVA followed by Tukey’s post hoc HSD for multiple comparisons, *P < 0.05 and **P < 0.01.

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