🧫
Closed-loop tFUS Enhances Glymphatic Clearance and Restores CA1 PV Interneuron Gamma in APP/PS1 Mice
active
experiment
Created: 2026-04-26T13:48:17
By: etl-v1-backfill
Quality:
50%
✓ SciDEX
ID: exp-proposal-6c20116f9a1b
🧫 Experiment Protocol
In VivoAlzheimer's diseasePVALBAPP/PS1 mice 8-11 months (n=10/group x 3 groups) with hippocampal LFP implants; MRI-guided tFUSabandoned
Test whether closed-loop tFUS (focused on dorsal hippocampus, 250 kHz, 2 Hz pulsed ISI phase-locked to slow oscillation) enhances AQP4-dependent glymphatic CSF influx, reduces perivascular Abeta load around PV+ interneurons, and restores CA1 gamma oscillation power in APP/PS1 mice.
PRIMARY OUTCOME
Perivascular Abeta load around PV+ cells reduced >=35%; CA1 gamma power restored to >=70% of WT
EXPECTED OUTCOMES
tFUS will increase glymphatic influx 2x (gadolinium signal), reduce PV-soma-adjacent Abeta >=35%, restore CA1 gamma >=70% WT, and improve Barnes maze latency.
SUCCESS CRITERIA
Primary: PV perisomatic Abeta area fraction reduced >=35% vs APP/PS1-sham (p<0.05). Secondary: CA1 gamma power >=70% of WT level; no T2 lesions on MRI.
PROTOCOL
1. APP/PS1 mice, 8 months, MRI-guided tFUS targeting dorsal CA1. 2. Closed-loop: slow-oscillation (0.5-1 Hz) detection -> tFUS pulse at up-state onset (250 kHz, 0.25 MPa, 200 ms duration, 2 Hz PRF) for 1 h during NREM (head-fixed). 3. 30 daily sessions; controls: sham-tFUS, WT-tFUS. 4. Endpoints: - MRI T1 with gadolinium intrathecal for glymphatic influx (CSF tracer distribution) - IHC: AQP4 polarisation (aquaporin-4 end-feet), PV+/Abeta co-staining, plaque load - LFP power spectral density (30-80 Hz gamma power in CA1) - Contextual fear conditioning, Barnes maze - Safety: GFAP reactivity, NeuN counts, MRI T2. 5. Primary: PV perisomatic Abeta area fraction; secondary: CA1 gamma power, glymphatic influx.
LINKED HYPOTHESES
Source: task:a989715e-c687-4558-91ca-74fce1474bd2
🧫 Experiment Extras
ESTIMATED COST
$125,000
TIMELINE
20 months
PATHWAY
Glymphatic AQP4 -> perivascular Abeta clearance -> PV interneuron perisomatic inhibition -> gamma oscillation
MARKET PRICE
$0.50
STATUS
abandoned
Scoring Dimensions
Prediction Markets (1 direct, 0 via hypothesis — 1 total)
Closed-loop transcranial focused ultrasound to restore hippocampal gamma oscillations via YES 75% · Liq $100 · active▸Metadataorigin_type: v1_polymorphic_backfill
| origin_type | v1_polymorphic_backfill |
| source_table | experiments |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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