Redefining the components of central CO(2) chemosensitivity – towards a better understanding of mechanism

ABSTRACT: The field of CO(2) chemosensitivity has developed considerably in recent years. There has been a mounting number of competing nuclei proposed as chemosensitive along with an ever increasing list of potential chemosensory transducing molecules. Is it really possible that all of these areas and candidate molecules are involved in the detection of chemosensory stimuli? How do we discriminate rigorously between molecules that are chemosensory transducers at the head of a physiological reflexversusthose that just happen to display sensitivity to a chemosensory stimulus? Equally, how do we differentiate between nuclei that have a primary chemosensory function, versusthose that are relays in the pathway? We have approached these questions by proposing rigorous definitions for the different components of the chemosensory reflex, going from the salient molecules and ions, through the components of transduction to the identity of chemosensitive cells and chemosensitive nuclei. Our definitions include practical and rigorous experimental tests that can be used to establish the identity of these components. We begin by describing the need for central CO(2) chemosensitivity and the problems that the field has faced. By comparing chemosensory mechanisms to those in the visual system we suggest stricter definitions for the components of the chemosensory pathway. We then, considering these definitions, re-evaluate current knowledge of chemosensory transduction, and propose the ‘multiple salient signal hypothesis’ as a framework for understanding the multiplicity of transduction mechanisms and brain areas seemingly involved in chemosensitivity.