Low-intensity focused ultrasound stimulation reverses social avoidance behavior in mice experiencing social defeat stress
Yimeng Wang, Yang Bai, Xi Xiao, Ling Wang, Ganjiang Wei, Mingkun Guo, Xizi Song, Yutao Tian, Dong Ming, Jiajia Yang, Chenguang Zheng
Cerebral Cortex 2022 · 10.1093/cercor/bhac037
Abstract
The excitatory neurons of the medial prefrontal cortex (mPFC) respond to social stimuli. However, little is known about how the neural activity is altered during social avoidance, and whether it could act as a target of low-intensity focused ultrasound stimulation (LIFUS) to rescue social deficits. The present study aimed to investigate the mechanisms of neuronal activities and inflammatory responses underlying the effect of LIFUS on social avoidance. We found that chronic LIFUS stimulation can effectively improve social avoidance in the defeated mice. Calcium imaging recordings by fiber photometry in the defeated mice showed inhibited ensemble activity during social behaviors. LIFUS instantaneously triggered the mPFC neuronal activities, and chronic LIFUS significantly enhanced their neuronal excitation related to social interactions. We further found that the excessive activation of microglial cells and the overexpression of the inflammation signaling, i.e. Toll-like receptors(TLR4)/nuclear factor-kappaB(NF-КB), in mPFC were significantly inhibited by LIFUS. These results suggest that the LIFUS may inhibit social avoidance behavior by reducing activation of the inflammatory response, increasing neuronal excitation, and protecting the integrity of the neuronal structure in the mPFC. Our findings raised the possibility of LIFUS being applied as novel neuromodulation for social avoidance treatment in neuropsychiatric diseases.
Abstract via europepmc.
Exposures
Exposure 1: chronic LIFUS to mPFC (PrL) in socially defeated mice
Target: ventromedial prefrontal cortex — “medial prefrontal cortex (mPFC)”
Device: Olympus / Panametrics · Olympus, USA · V318 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,500 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 15% | ⚑ |
| Sonication duration (s) | 0.5 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| 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 | |
| Ispta, domain unspecified (W/cm²) | 0.015 | ✓✓✓⚑ |
0.5 MHz, 1.5 kHz PRF, 50 cycles (0.1 ms tone burst), 0.5 s sonication duration, 2 s interstimulation interval, Ispta 15 mW/cm2; 15 min per day under isoflurane, delivered 5 h after stress exposure on the first 10 days and continued for 3 further weeks. Sham: transducer 5 cm from the head.
Flags from extraction
n_subjects— Only the FUS group (n = 17) received ultrasound; 62 C57BL/6J mice were used in total including controls, and some analyses use subsets (e.g. n = 4 per group for photometry).n_sessions_per_subject— Text says LIFUS was daily for 31 days written as '10 days + 3 weeks' (symbol lost in extraction); 31 recorded as stated.exposures[0].timing.duty_cycle_pct— Duty cycle is not stated.exposures[0].unspecified_domain.ispta_w_cm2— 15 mW/cm2 converted to W/cm2; domain not stated (attenuation through skull to about 47.76% was measured separately, no in-situ value given).exposures[0].timing.sonication_duration_s— Acute photometry during-LIFUS recordings are described over a 13-min stimulation period; the 0.5 s per-sonication value from the chronic parameters is recorded.exposures[0].target— Target described as the PrL area of the mPFC, mapped to ventromedial_prefrontal_cortex via the mPFC synonym.