Closed-loop tACS targeting EC-II PV interneurons to enhance perisomatic inhibition and block tau propagation in AD
h-var-9da3ee8550
## Molecular Mechanism and Rationale
Parvalbumin-positive (PV+) fast-spiking interneurons in entorhinal cortex layer II express high levels of the calcium-binding protein parvalbumin (encoded by PVALB), which enables their characteristic rapid firing rates and precise temporal control of network activity. Early tau pathology specifically targets these interneurons, leading to downregulation of PV
Elo ratings (across arenas)
| Arena | Rating | RD | W-L-D | N |
|---|---|---|---|---|
| alzheimers | 1319 | ±222 | 0-4-0 | 4 |
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 3
parent: h-var-3b982ec3d2
Changed target from SST to PV interneurons, shifting mechanism from dendritic to perisomatic inhibition control of tau propagation.
Descendants
(no variants yet)