The authors importantly demonstrate chemosensory responses of neurons in the retrotrapezoid nucleus-RTN, Raphe magnus and pallidus nuclei, and lateral parafacial region- pFL, and they describe regional heterogeneity of cellular responses to hypercapnia in these regions with important functional implications. This paper presents a novel application of endoscopic imaging with miniscopes in awake-behaving mice to address the important problem of analyzing multicellular activity by calcium activity imaging within circumscribed regions of the medulla oblongata that are proposed to have chemosensory functions for the homeostatic regulation of breathing in response to elevated systemic CO2 (hypercapnia). Our analysis revises the understanding of chemosensory control in awake adult mouse and paves the way to understanding how breathing is coordinated with complex non-ventilatory behaviours. Our data show that chemosensory responses in the RTN and Raphe differ in their temporal characteristics and sensitivity to CO 2, raising the possibility these nuclei act in a coordinated way to generate adaptive ventilatory responses to hypercapnia. ![]() Activity in the pF L supports its role as a homogenous neuronal population that drives active expiration. Here, we use GCaMP6 expression and head-mounted mini-microscopes to image Ca 2+ activity in these nuclei in awake adult mice during hypercapnia. ![]() Hypercapnia also induces active expiration, an adaptive change thought to be controlled by the lateral parafacial region (pF L). In the medulla oblongata, the retrotrapezoid nucleus (RTN) and rostral medullary Raphe are proposed as CO 2 chemosensory nuclei mediating adaptive respiratory changes. Regulation of systemic PCO 2 is a life-preserving homeostatic mechanism.
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