CGRP reception potentiates anxiety in an influenza A derived immune engram.

An immune engram is a recently described phenomenon in which neuronal populations encode functional aspects of an immune challenge. Here we investigate an immune engram arising from respiratory infection with influenza A virus, demonstrating a molecular mechanism with differential influence over behavioral and immunological aspects of the engram. We first define a cellular response to acute non-neurotropic influenza A/Puerto Rico/8/1934 (PR8) infection by mapping cFos+ cells and microglia morphology across brain regions. In the posterior insula, this response has an early peak at 3 days post infection. Using a cre-dependent excitatory chemogenetic system in TRAP2 mice, we capture an engram at this same region and infection timepoint. Activation of this PR8 engram results in anxiety behavior and increased transcriptional expression of cytokines in lung tissue but not spleen tissue. We further explore how pulmonary signals contribute to this PR8 engram. Using tissue-specific, cre-dependent expression of diphtheria toxin fragment in