Closed-loop tACS targeting EC-II parvalbumin interneurons to restore gamma rhythmogenesis and block tau AIS disruption in AD
h-var-4eca108177
## Molecular Mechanism and Rationale
Parvalbumin-positive (PV+) fast-spiking interneurons in entorhinal cortex layers II-III generate perisomatic gamma oscillations through precisely timed GABA release at basket cell synapses and axon initial segment (AIS) contacts via chandelier cells. In Alzheimer's disease, hyperphosphorylated tau disrupts the subcellular localization of AnkyrinG, a critical s
Elo ratings (across arenas)
| Arena | Rating | RD | W-L-D | N |
|---|---|---|---|---|
| global | 1770 | ±140 | 8-2-0 | 10 |
| alzheimers | 1723 | ±81 | 18-18-0 | 36 |
| loop:loop-74f20cb27aad | 1423 | ±298 | 0-1-0 | 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 3
parent: h-var-3b982ec3d2
Replaces SST dendrite-projecting interneurons with PV fast-spiking basket/chandelier cells as the target, shifting the mechanism from gain-control of stellate cell burst firing to perisomatic gamma rh
Descendants
(no variants yet)