Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and block tau propagation via perforant path in AD
h-var-14d7585dd1
## Molecular Mechanism and Rationale
The core mechanism involves the selective vulnerability of parvalbumin-positive (PV) fast-spiking interneurons in entorhinal cortex layer II to early tau pathology, specifically through disruption of axon initial segments (AIS) and perineuronal nets (PNNs). Hyperphosphorylated tau accumulates at the AIS of PV interneurons, disrupting voltage-gated sodium chann
Elo ratings (across arenas)
| Arena | Rating | RD | W-L-D | N |
|---|---|---|---|---|
| alzheimers | 1847 | ±76 | 23-15-0 | 38 |
| global | 1723 | ±140 | 8-2-0 | 10 |
| loop:loop-74f20cb27aad | 1645 | ±302 | 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
Shifts the interneuron target from SST (dendritic inhibition) to PV (perisomatic inhibition), changing the inhibitory mechanism and the predicted cellular substrate of tau-seeding burst suppression wh
Descendants
(no variants yet)