Transcranial focused ultrasound (tFUS) targets deep brain areas by non-invasively administering low intensity ultrasound through the brain with a high spatial resolution (Zhang et al., 2021). Previous results indicate that stimulating neural cells at specific pulsing frequencies is neuroprotective (Manippa et al., 2022). We were therefore interested in determining whether a similar approach could be taken with focused ultrasound stimulation. To this end, we prepared acute rat hippocampal slices and exposed them to 40Hz pulsing ultrasound for 1hr. Following a proteomics screen, we noted an increase in brain-derived neurotrophic factor (BDNF)-related signalling after ultrasound exposure. In support of this, we found that ultrasound-exposed slices had an increased abundance of BDNF protein, as shown by Western blotting. Finally, we wanted to determine whether this ultrasound-induced increase in BDNF had any consequences for synaptic function. We therefore performed field excitatory post-synaptic potential electrophysiology recording, finding that ultrasound exposure did not negatively impact on synaptic function. Together, our data indicate that a particular pulsing regime of ultrasound stimulation induces an upregulation of neurotrophic signalling in acute hippocampal brain tissue. This supports the notion that tFUS has the potential to be used as a therapeutic intervention where enhancing neurotrophic factor production would be beneficial.Manippa et al. (2022). An update on the use of gamma (multi)sensory stimulation for Alzheimer’s disease treatment. Frontiers in Aging Neuroscience https://doi.org/10.3389/fnagi.2022.1095081Zhang et al. (2021).Transcranial Focused Ultrasound Neuromodulation: A Review of the Excitatory and Inhibitory Effects on Brain Activity in Human and Animals. Frontiers in Human Neuroscience https://doi.org/10.3389/fnhum.2021.749162