Closed-loop focused ultrasound targeting EC-II SST interneurons to restore gamma gating and block tau propagation in AD
h-var-55da4f915d
## Molecular Mechanism and Rationale
Somatostatin-positive (SST) interneurons in entorhinal cortex (EC) layer II serve as critical gamma frequency gatekeepers that regulate perforant path transmission to the hippocampus through perisomatic inhibition of stellate cells. These parvalbumin-negative interneurons express voltage-gated calcium channels and mechanosensitive ion channels that respond to
Elo ratings (across arenas)
| Arena | Rating | RD | W-L-D | N |
|---|---|---|---|---|
| alzheimers | 2114 | ±84 | 33-7-0 | 40 |
| global | 1850 | ±144 | 8-2-0 | 10 |
| loop:loop-74f20cb27aad | 1626 | ±294 | 0-0-1 | 1 |
Ancestry (oldest → this)
mutate · gen 1
parent: h-bdbd2120
Perturbs intervention and mechanism: replaces open-loop sensory flickering with closed-loop tACS phase-locked to hippocampal theta, targeting the CA1 PV–SST microcircuit for precision gamma restoratio
mutate · gen 2
parent: h-var-d749cd28cb
Shifts the intervention scope from CA1–mPFC to entorhinal cortex layer II and reframes the evidence angle from SST degeneration-induced gamma loss to SST rescue as a mechanism for blocking trans-synap
mutate · gen 4
parent: h-var-3b982ec3d2
Replaces tACS with closed-loop transcranial focused ultrasound (tFUS), shifting the intervention mechanism from electromagnetic entrainment to mechanosensitive PIEZO1/TREK-1 channel-mediated SST inter
Descendants
1515 (8 matches)
1449 (11 matches)
1228 (3 matches)
1698 (8 matches)
1500 (0 matches)
1500 (0 matches)