ATF3-based peripheral neural tract tracing.

Abstract

Defining neural connectivity between peripheral organs and the nervous system remains a fundamental challenge. While neural tract tracing techniques are well established and highly effective in the central nervous system, their application in peripheral tissues-particularly through retrograde approaches-continues to generate controversy. This article highlights an alternative approach based on the neuronal injury response. Specifically, I discuss the use of activating transcription factor 3 (ATF3), a molecular marker robustly upregulated in neurons following axonal injury, as an indirect means of identifying organ-specific innervation. By integrating classical and injury-induced approaches, this framework may help resolve longstanding debates regarding visceral innervation and improve the reliability of circuit-mapping strategies in the peripheral nervous system.