A Minimal Transcriptional Footprint of Endogenous Cholinergic Signaling in the Hippocampus After Acute and Repeated Forced Swim Stress

This divergence unveiled a cryptic post-transcriptional cholinergic function: although Egr1 mRNA was robustly induced by FSS in lesioned animals, Egr1 protein synthesis was entirely abolished. Thus, septohippocampal acetylcholine does not act as a broad permissive signal for neuronal activation, but rather as a dual-tiered regulator—selectively gating transcription of a core plasticity module while uniquely licensing Egr1 translation.

These findings reframe cholinergic signaling from a global transcriptional driver to a context-dependent molecular switch, reconciling prior contradictions and implicating translational dysregulation as a mechanism in cholinergic dysfunction.