Scanning Ultrasound (SUS) Causes No Changes to Neuronal Excitability and Prevents Age-Related Reductions in Hippocampal CA1 Dendritic Structure in Wild-Type Mice
Robert John Hatch, Gerhard Leinenga, Jürgen Götz
PLOS ONE 2016 · 10.1371/journal.pone.0164278
Abstract
Scanning ultrasound (SUS) is a noninvasive approach that has recently been shown to ameliorate histopathological changes and restore memory functions in an Alzheimer's disease mouse model. Although no overt neuronal damage was reported, the short- and long-term effects of SUS on neuronal excitability and dendritic tree morphology had not been investigated. To address this, we performed patch-clamp recordings from hippocampal CA1 pyramidal neurons in wild-type mice 2 and 24 hours after a single SUS treatment, and one week and 3 months after six weekly SUS treatments, including sham treatments as controls. In both treatment regimes, no changes in CA1 neuronal excitability were observed in SUS-treated neurons when compared to sham-treated neurons at any time-point. For the multiple treatment groups, we also determined the dendritic morphology and spine densities of the neurons from which we had recorded. The apical trees of sham-treated neurons were reduced at the 3 month time-point when compared to one week; however, surprisingly, no longitudinal change was detected in the apical dendritic trees of SUS-treated neurons. In contrast, the length and complexity of the basal dendritic trees were not affected by SUS treatment at either time-point. The apical dendritic spine densities were reduced, independent of the treatment group, at 3 months compared to one week. Collectively, these data suggest that ultrasound can be employed to prevent an age-associated loss of dendritic structure without impairing neuronal excitability.
Abstract via europepmc.
Exposures
Exposure 1: Scanning ultrasound (SUS) treatment of the whole brain with microbubbles
Target: whole brain or unfocused — “the entire brain”
Device: Philips Research · Philips Research · Therapy Imaging Probe System (TIPS) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,000 | ✓✓✓ |
| Pulse duration (ms) | 10 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 6 | ✓✓✓ |
| Free-field pressure (kPa) | 700 | ✓✓✓⚑ |
|---|---|---|
| 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 |
Ultrasound was applied sequentially in a scanning mode by applying it for 6 seconds duration per spot, moving the focus 1.5 mm and repeating the application until the entire brain was treated as described previously. The focus of the transducer had a volume of 1.5 mm x 1.5 mm x 12 mm. Mice received either a single SUS treatment (analysed 2 or 24 hours later) or six weekly SUS treatments (analysed one week or three months after the final treatment).
Flags from extraction
n_subjects— Paper states total mice (24) split 3 sham/3 SUS per each of 4 protocols; recorded as group sizes for the SUS-exposed arm only (3x4), not summed, and total includes an equal number of sham mice not exposed to ultrasound.exposures[0].free_field.pressure_kpa— Paper states 0.7 MPa peak rarefactional pressure 'applied outside the skull' without stating whether this was a water-tank/free-field measurement; recorded as free_field because it is explicitly outside the skull (not in-situ), but the domain wording is not the paper's usual 'measured in water' phrasing.exposures[0].target— Ultrasound was scanned over the entire brain (BBB-opening protocol); readouts were specifically from hippocampal CA1 neurons, but the sonication itself was not targeted to the hippocampus.