Low-intensity transcranial ultrasound stimulation promotes the extinction of fear memory through the BDNF-TrkB signaling pathway
Degong Meng, Cong Zhang, Jiamin Pei, Xiao Zhang, Hanna Lu, Hui Ji, Xiangjian Zhang, Yi Yuan
NeuroImage 2025 · 10.1016/j.neuroimage.2025.121441
Abstract
Synaptic plasticity plays a crucial role in the extinction of fearful memories. Low-intensity transcranial ultrasound stimulation (TUS) can modulate synaptic plasticity and promote the extinction of fear memories. However, the mechanism by which TUS promotes the extinction of fear memory remains unclear. This study aimed to explore whether and how synaptic plasticity under TUS is involved in modulating fear memory and the role of the brain-derived neurotrophic factor (BDNF)-the tropomyosin-related kinase B (TrkB) signaling pathway in this process. We used behavioral tests and two-photon fluorescence imaging to investigate the modulatory effects of TUS on fear memory and examined the formation/elimination of dendritic spines and the calcium activity of pyramidal neurons in the prefrontal cortex in mice in vivo. We found that TUS of the prefrontal cortex can promote fear memory extinction in mice while promoting dendritic spine formation, reducing dendritic spine elimination, increasing pyramidal neuron activity, and enhancing the expression of BDNF and its receptor TrkB. Conversely, inhibiting the BDNF-TrkB signaling pathway weakened these effects of ultrasound stimulation. Our study demonstrated that TUS could promote the extinction of fear memories, indicating that TUS has the potential to be used in the clinical treatment of patients with fear memory.
Abstract via europepmc.
Exposures
Exposure 1: TUS of FrA
Target: prefrontal cortex — “FrA”
Device: Olympus / Panametrics · Olympus · V302-SU
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 50 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 300 | ✓✓✓⚑ |
| 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 | |
| Pressure, domain unspecified (kPa) | 200 | ✓✓✓⚑ |
| Isppa, domain unspecified (W/cm²) | 8.6 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.43 | ✓✓✓ |
Each session consisted of 5 min of stimulation followed by a 5-minute pause, repeated for a total of three 25-minute groups; 30 min of TUS applied once before fear extinction (D2); sham with signal source output switched off.
Consistency checks: intensity pressure inconsistent unspecified domain.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Paper states NC/p = 50,000 cycles at 1 MHz and 'stimulation time SD = 50 ms' with PRF 1 Hz and DC 5 %; recorded 50 ms as the pulse duration (matches DC/PRF) but the paper does not label it a pulse duration.exposures[0].timing.sonication_duration_s— Taken from '5 min of stimulation' followed by a 5 min pause, repeated to a 25-minute total; the structure within the 5 min is not described beyond PRF 1 Hz.exposures[0].unspecified_domain.pressure_kpa— Pressure and intensities stated without saying where they apply (COMSOL simulation of the field is mentioned).n_sessions_per_subject— Number of TUS sessions per animal not clearly stated.auditory_control— Paper lists lack of active control at a non-target site and possible auditory confounds as a limitation; no auditory control was done.anaesthesia— Mice awake during imaging; state during TUS not stated.