A minimal E/I circuit model explains differential recovery from amblyopia under TTX and reverse occlusion
Abstract
Recovery from amblyopia beyond the critical period remains a major challenge in visual neuroscience. Experimental studies show that transient inactivation of the fellow eye with tetrodotoxin (TTX) produces stronger and more persistent recovery than reverse occlusion (RO), despite both interventions reducing competition from the fellow eye. The circuit mechanisms underlying this difference remain unclear. We develop a minimal cortical circuit model combining excitatory-inhibitory population dynamics, BCM-like metaplasticity, homeostatic regulation, and eye-specific synaptic plasticity. Monocular deprivation drives the network into an amblyopic operating regime with reduced excitatory activity and fellow-eye dominance. Phase-plane and operating-regime analyses show that TTX and RO subsequently place the circuit in distinct dynamical states. TTX lowers inhibitory activity while maintaining excitatory activity above the BCM modification threshold, creating a larger plasticity-permissive regime than RO. These differences produce stronger recovery of amblyopic-eye responsiveness and greater correction of ocular dominance under TTX. A local robustness analysis across 300 perturbed parameter sets shows that the TTX advantage is not dependent on a narrowly tuned parameter choice. These results provide a mechanistic account of the differential efficacy of fellow-eye inactivation and suggest that recovery from sensory deprivation depends not only on changes in sensory input, but also on the dynamical operating regime of the cortical circuit.
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BibTeX
@misc{udeigwe2026minimal,
title = {{A minimal E/I circuit model explains differential recovery from amblyopia under TTX and reverse occlusion}},
author = {Lawrence Udeigwe},
howpublished = {arXiv},
year = {2026},
month = nov,
doi = {10.48550/arxiv.2611.06189},
eprint = {2611.06189},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2611.06189},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - A minimal E/I circuit model explains differential recovery from amblyopia under TTX and reverse occlusion
AU - Lawrence Udeigwe
PY - 2026
DA - 2026/11/04
PB - arXiv
DO - 10.48550/arxiv.2611.06189
UR - https://arxiv.org/abs/2611.06189
AB - Recovery from amblyopia beyond the critical period remains a major challenge in visual neuroscience. Experimental studies show that transient inactivation of the fellow eye with tetrodotoxin (TTX) produces stronger and more persistent recovery than reverse occlusion (RO), despite both interventions reducing competition from the fellow eye. The circuit mechanisms underlying this difference remain unclear. We develop a minimal cortical circuit model combining excitatory-inhibitory population dynamics, BCM-like metaplasticity, homeostatic regulation, and eye-specific synaptic plasticity. Monocular deprivation drives the network into an amblyopic operating regime with reduced excitatory activity and fellow-eye dominance. Phase-plane and operating-regime analyses show that TTX and RO subsequently place the circuit in distinct dynamical states. TTX lowers inhibitory activity while maintaining excitatory activity above the BCM modification threshold, creating a larger plasticity-permissive regime than RO. These differences produce stronger recovery of amblyopic-eye responsiveness and greater correction of ocular dominance under TTX. A local robustness analysis across 300 perturbed parameter sets shows that the TTX advantage is not dependent on a narrowly tuned parameter choice. These results provide a mechanistic account of the differential efficacy of fellow-eye inactivation and suggest that recovery from sensory deprivation depends not only on changes in sensory input, but also on the dynamical operating regime of the cortical circuit.
ER -