🧫

tFUS Targeting EC-II SST Interneurons Restores Hippocampal-Prefrontal Gamma Sync in hAPP-J20 Mice

active
experiment Created: 2026-04-26T13:48:17 By: etl-v1-backfill Quality: 50% ✓ SciDEX ID: exp-proposal-f6ba02628d67
🧫 Experiment Protocol In VivoAlzheimer's diseaseSSThAPP-J20 mice (n=10/group x 3 groups) with chronic LFP implants in CA1, mPFC, and EC-IIabandoned
Determine whether closed-loop transcranial focused ultrasound (tFUS, 250 kHz, 500 ms pulses phase-locked to hippocampal theta) targeting entorhinal cortex layer II SST+ interneurons restores hippocampal-prefrontal gamma synchrony and improves spatial working memory in hAPP-J20 AD mice.
PRIMARY OUTCOME
CA1-mPFC gamma coherence (30-80 Hz) >=2x vehicle during theta phase; Y-maze alternation >=65%
EXPECTED OUTCOMES
Closed-loop tFUS will increase gamma coherence >=2x, drive SST interneuron firing phase-locked to theta, restore Y-maze alternation to >=65%, and produce no BBB disruption.
SUCCESS CRITERIA
Primary: CA1-mPFC gamma coherence >=2x vehicle (paired t-test p<0.05). Secondary: Y-maze alternation >=65%; Evans blue negative (no BBB disruption).
PROTOCOL
1. Implant LFP/unit recording arrays in EC-II, CA1, mPFC at 3 months hAPP-J20. 2. Closed-loop tFUS system: real-time theta detection (Hilbert transform, 4-12 Hz), trigger tFUS pulse (250 kHz, 0.3 MPa, 500 ms) at theta trough targeting EC-II. 3. 20 daily sessions (1 h each) vs sham-tFUS controls. 4. Endpoints: - LFP coherence spectral analysis (CA1-mPFC, 30-80 Hz) - Single-unit SST interneuron firing (juxtasomal recording) - Y-maze, novel object location (NOL) - IHC: SST+/cFos+ co-labelling, c-Fos in EC-II - Safety: Evans blue BBB permeability, H+E histology. 5. Primary: coherence; secondary: SST firing rate, Y-maze, BBB integrity.
Source: task:a989715e-c687-4558-91ca-74fce1474bd2
🧫 Experiment Extras
ESTIMATED COST
$110,000
TIMELINE
22 months
PATHWAY
EC-II SST interneuron -> theta-gamma coupling -> hippocampal-prefrontal synchrony
MARKET PRICE
$0.50
STATUS
abandoned
Scoring Dimensions
Info Gain 0.89 (25%) Feasibility 0.48 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.88 (10%) Ethical Safety 0.00 (10%)0.744composite
Related Target
SSTcomposite 0.527
Metadataorigin_type: v1_polymorphic_backfill
origin_typev1_polymorphic_backfill
source_tableexperiments
_schema_version1
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting 0 contradicting 0 neutral
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