Ultrasound Stimulation Attenuates CRS-Induced Depressive Behavior by Modulating Dopamine Release in the Prefrontal Cortex
Ling Wang, Sutong Wang, Weiyi Mo, Yaqing Li, Qing Yang, Yutao Tian, Chenguang Zheng, Jiajia Yang, Dong Ming
IEEE Transactions on Neural Systems and Rehabilitation Engineering 2024, 32, 1314-1323 · 10.1109/tnsre.2024.3378976
Abstract
Depression is one of the most serious mental disorders affecting modern human life and is often caused by chronic stress. Dopamine system dysfunction is proposed to contribute to the pathophysiology of chronic stress, especially the ventral tegmental area (VTA) which mainly consists of dopaminergic neurons. Focused ultrasound stimulation (FUS) is a promising neuromodulation modality and multiple studies have demonstrated effective ultrasonic activation of cortical, subcortical, and related networks. However, the effects of FUS on the dopamine system and the potential link to chronic stress-induced depressive behaviors are relatively unknown. Here, we measured the effects of FUS targeting VTA on the improvement of depression-like behavior and evaluated the dopamine concentration in the downstream region - medial prefrontal cortex (mPFC). We found that targeting VTA FUS treatment alleviated chronic restraint stress (CRS) -induced anhedonia and despair behavior. Using an in vivo photometry approach, we analyzed the dopamine signal of mPFC and revealed a significant increase following the FUS, positively associated with the improvement of anhedonia behavior. FUS also protected the dopaminergic neurons in VTA from the damage caused by CRS exposure. Thus, these results demonstrated that targeting VTA FUS treatment significantly rescued the depressive-like behavior and declined dopamine level of mPFC induced by CRS. These beneficial effects of FUS might be due to protection in the DA neuron of VTA. Our findings suggest that FUS treatment could serve as a new therapeutic strategy for the treatment of stress-related disorders.
Abstract via europepmc.
Exposures
Exposure 1: FUS targeting ventral tegmental area (VTA)
Target: ventral tegmental area — “ventral tegmental area (VTA)”
Device: Olympus / Panametrics · Olympus · V318 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.3 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,500 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 45% | ⚑ |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.15 | ✓✓✓ |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.09 | ✓✓✓ |
150-cycle tone bursts with a 1.6-s stimulation interval; the transducer was affixed above the mouse head at 30 degrees to the skull surface targeting the VTA; FUS was performed for 15 min each day for 10 days under isoflurane anesthesia.
Flags from extraction
exposures[0].timing.duty_cycle_pct— Paper reports pulse repetition frequency (1.5 kHz) and tone-burst duration (0.3 ms) separately but never states a duty cycle percentage; not computed per protocol.anaesthesia— Mice were anesthetized with isoflurane during FUS delivery but awake during behavioral testing, hence coded as both.