Use-dependent learning and memory of the Hering-Breuer inflation reflex in rats

The classic Hering-Breuer inflation reflex (HBIR) is a widely held tenet for understanding the lung volume-related vagal control of respiratory rhythm. Recent evidence, however, has revealed that the fictive HBIR elicited by electrical vagal stimulation in rats is not static but may be attenuated centrally by two forms of non-associative learning (habituation and desensitization) that continually mitigate the reflex effects with exponential adaptations like a differentiator or high-pass filter. Desensitization is analogous to habituation but exhibits an explicit short-term memory (STM) in the form of a rebound response with exponential decay during recovery from stimulation. To investigate whether such learning and memory effects are lung volume related and use-dependent (practice makes perfect), we compared the time-dependent changes in inspiratory and expiratory durations (t(I) and t(E)) during and after 1 or 8 min unilateral lung inflation or high-frequency, low-intensity vagal stimulation in anaesthetized, uni- or bi-vagotomized rats. Unilateral lung inflation and vagal stimulation both elicited abrupt shortening of t(I) and lengthening of t(E) (HBIR effects) and gradual habituation and desensitization throughout the 1 or 8 min test period, followed by rebound responses in t(I) and t(E) with exponential recovery (STM effects) in the post-test period. In both cases, the STM time constants for t(I) and t(E) were significantly longer with the 8 min test than with the 1 min test (17-45 versus 4-11 s, P < 0.01). We conclude that the HBIR and its central habituation and desensitization are mediated peripherally by lung volume-related vagal afferents, and that the STM of desensitization is use-dependent. The translational implications of these findings are discussed.