CGRP reception potentiates anxiety in an influenza A derived immune engram

We further explore how pulmonary signals contribute to this PR8 engram. Using tissue-specific, cre-dependent expression of diphtheria toxin fragment in Calcacre mice, we ablate calca-expressing cells including pulmonary neuroendocrine cells in respiratory tissue. Loss of calca-expressing cells prevents changes in synaptic engulfment by microglia in the insula during PR8 infection without altering the cellular response to infection in pulmonary tissue.

Signaling of calcitonin gene related peptide (CGRP), a peptide encoded by calca, can be blocked with the small molecule CGRP receptor antagonist rimegepant. Using rimegepant during acute PR8 infection we again demonstrate that loss of calca signaling prevents the cellular response to PR8 infection in the insula. Finally, applying rimegepant alongside the chemogenetic system in TRAP2 mice we show that CGRP receptor antagonism during engram formation prevents anxiety behavior but not peripheral gene expression changes resulting from PR8 engram activation.