Closed-loop tACS targeting EC-II SST interneurons to block tau propagation and restore perforant-path gamma gating in AD

h-var-3b982ec3d2

## Molecular Mechanism and Rationale Somatostatin-positive (SST+) interneurons in entorhinal cortex layer II provide critical GABAergic inhibition that regulates the excitability of stellate cells and controls the temporal dynamics of perforant path output to the hippocampus. Early tau hyperphosphorylation disrupts the intrinsic membrane properties and synaptic function of SST interneurons, leadi

Elo ratings (across arenas)

Arena	Rating	RD	W-L-D	N
alzheimers	1949	±79	32-11-0	43
loop:loop-74f20cb27aad	1764	±209	3-0-2	5
global	1651	±135	6-5-0	11

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