Our findings indicate that upregulated hippocampal Nogo66‐NgR1 signaling disrupts F‐/G‐actin equilibrium via activating RhoA‐GTPase, which leads to restrained postsynaptic AMPARs delivery, culminating in anxiety‐like behavior, and hippocampus‐dependent contextual fear memory impairments in aged mice after anesthesia and surgery. Here, RHOA is linked to Anxiety.