Low-intensity focused ultrasound ameliorates depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway
Faqi Wang, Qiuquan Cai, Rongfang Ju, Sutong Wang, Lu Liu, Meiyi Pan, Ning Sun, Xiunan Wang, Ling Wang, Jiajia Yang, Chenguang Zheng, Dong Ming
Cerebral Cortex 2023, 33, 8024-8034 · 10.1093/cercor/bhad095
Abstract
It is of great social significance and clinical value to explore new effective treatments for depression. Low-intensity focused ultrasound stimulation (LIFUS) has been indicated to have notable neuroprotective effects on depression. However, little is known about how different strategies of LIFUS affect the therapeutic effect. Therefore, the purpose of this study is to investigate whether the effects of LIFUS on depression-like behaviors are associated with the intensity and the underlying mechanisms. We established the depression rats model using the chronic unpredictable stress (CUS) and applied the LIFUS with high/low intensity (Ispta = 500 and 230 mW/cm2, respectively) to the left medial prefrontal cortex (mPFC) after CUS. We found that two intensities of LIFUS both could significantly improve depression-like behaviors to a comparable degree. We further found that theta oscillation synchronization and synaptic functional plasticity in the hippocampal vCA1-mPFC pathway were significantly improved by chronic LIFUS which mainly due to the alternation of synaptic structural plasticity and the expression of post-synaptic proteins in the mPFC. These results suggest that LIFUS ameliorates the depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway. Our study provides preclinical evidence and a theoretical basis for applying LIFUS for depression treatment.
Abstract via europepmc.
Exposures
Exposure 1: LIFUS to left medial prefrontal cortex, high (500 mW/cm2) and low (230 mW/cm2) intensity
Target: ventromedial prefrontal cortex — “left medial prefrontal cortex (mPFC)”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.3 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 2,000 | ✓✓✓ |
| Duty cycle (%) | 60pulse duration × PRF gives 60% | ✓✓✓ |
| Sonication duration (s) | 0.5 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.5, 0.23swept | ✓✓✓ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
LIFUS (0.5 MHz, 2 kHz PRF, 60% duty cycle, 0.3 ms tone-burst duration, 0.5 s sonication duration) delivered with a 2 s inter-stimulus interval, applied for 15 min daily for two consecutive weeks after chronic unpredictable stress (CUS) modelling, in two separate batches using 500 mW/cm2 (n=8 exposed) or 230 mW/cm2 (n=9 exposed) intensity; control/CUS-only groups received sham LIFUS.
Flags from extraction
n_subjects— Paper reports only the two intensity-group sizes (n=8 for 500 mW/cm2 batch, n=9 for 230 mW/cm2 batch) exposed to real LIFUS; never states a combined total.n_sessions_per_subject— Text states LIFUS was applied daily for two consecutive weeks, implying 14 sessions, but does not state a session count explicitly.sham_type— 'sham LIFUS' is mentioned but its mechanism (inactive transducer, etc.) is not described.exposures[0].device.family— No transducer manufacturer/model given; only the hydrophone (NH4000, Precision Acoustics) used for calibration is named.