Carotid sinus nerve transection abolishes the facilitation of breathing that occurs upon cessation of a hypercapnic gas challenge in male mice.

Arterial pCO elevations increase minute ventilation via activation of chemosensors within the carotid body (CB) and brainstem. Although the roles of CB chemoafferents in the hypercapnic (HC) ventilatory response have been investigated, there are no studies reporting the role of these chemoafferents in the ventilatory responses to a HC challenge or the responses that occur upon return to room air, in freely moving mice. This study found that an HC challenge (5% CO, 21% O, 74% N for 15 min) elicited an array of responses, including increases in frequency of breathing (accompanied by decreases in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives in sham-operated (SHAM) adult male C57BL6 mice, and that return to room air elicited a brief excitatory phase followed by gradual recovery of all parameters toward baseline values over a 15-min period. The array of ventilatory responses to the HC challenge in mice with bilateral carotid sinus nerve transection (CSNX) performed 7 days previously occurred more slowly but reached similar maxima as SHAM mice. A major finding was responses upon return to room air were dramatically lower in CSNX mice than SHAM mice, and the parameters returned to baseline values within 1-2 min in CSNX mice, whereas it took much longer in SHAM mice. These findings are the first evidence that CB chemoafferents play a key role in initiating the ventilatory responses to HC challenge in C57BL6 mice and are essential for the expression of post-HC ventilatory responses. This study presents the first evidence that carotid body chemoafferents play a key role in initiating the ventilatory responses, such as increases in frequency of breathing, tidal volume, and minute ventilation that occur in response to a hypercapnic gas challenge in freely moving C57BL6 mice. Our study also demonstrates for the first time that these chemoafferents are essential for the expression of the ventilatory responses that occur upon return to room air in these mice.