Invited Review: Plasticity in the control of breathing following sensory denervation

Abstract

Forster, H. V. Invited Review: Plasticity in the control of breathing following sensory denervation. J Appl Physiol 94: 784-794, 2003; 10.1152/japplphysiol.00602.2002.-The purpose of this manuscript is to review the results of studies on the recovery or plasticity following a denervation-or lesion-induced change in breathing. Carotid body denervation (CBD), lung denervation (LD), cervical (CDR) and thoracic (TDR) dorsal rhizotomy, dorsal spinal column lesions, and lesions at pontine, medullary, and spinal sites all chronically alter breathing. The plasticity after these is highly variable, ranging from near complete recovery of the peripheral chemoreflex in rats after CBD to minimal recovery of the Hering-Breuer inflation reflex in ponies after LD. The degree of plasticity varies among the different functions of each pathway, and plasticity varies with the age of the animal when the lesion was made. In addition, plasticity after some lesions varies between species, and plasticity is greater in the awake than in the anesthetized state. Reinnervation is not a common mechanism of plasticity. There is evidence supporting two mechanisms of plasticity. One is through upregulation of an alternate sensory pathway, such as serotonin-mediated aortic chemoreception after CBD. The second is through upregulation on the efferent limb of a reflex, such as serotonin-mediated increased responsiveness of phrenic motoneurons after CDR, TDR, and spinal cord injury. Accordingly, numerous components of the ventilatory control system exhibit plasticity after denervation or lesion-induced changes in breathing; this plasticity is uniform neither in magnitude nor in underlying mechanisms. A major need in future research is to determine whether "reorganization" within the central nervous system contributes to plasticity following lesion-induced changes in breathing.receptors; recovery of function; redundancy; chemoreflexes; mechanoreflexes DENERVATION OR LESIONING OF a receptor or neural pathway that normally contributes to the regulation of a physiological function will result in loss of or altered function. Thereafter, a time-dependent recovery of function is a manifestation of plasticity within the regulatory system. The purpose of this review is to summarize research on this type of plasticity within the system regulating breathing. Lesions are one of several means of inducing plasticity; a review of these and a general discussion of plasticity are presented elsewhere (66). Nevertheless, it seems appropriate to emphasize here that recovery of function can be due to restoration of the same mechanism or substitution of another mechanism. Also, recovery refers specifically to the return of a function, whereas plasticity refers to the process or mechanism of the restoration (i.e., capability of building new tissue or formative). A related phenomenon, redundancy, refers to two or more mechAddress for reprint requests and other correspondence:

Carotid body denervation alters ventilatory responses to ibotenic acid injections or focal acidosis in the medullary raphe

“…control of breathing; CO 2 chemoreception; peripheral chemoreception ONE ROLE OF THE PERIPHERAL chemoreceptors, or carotid bodies, relates to the ability to respond to changes in arterial O 2 and CO 2 , providing error feedback to the ventilatory control system (5, 13, 23). Additionally, the carotid bodies appear to provide a tonic excitatory input into the ventilatory control system, as evidenced by the effects of carotid body denervation (CBD) studies (7,12,19). CBD leads to hypoventilation during eupnea and exercise and to a reduction in CO 2 sensitivity.…”

“…Additionally, the carotid bodies appear to provide a tonic excitatory input into the ventilatory control system, as evidenced by the effects of carotid body denervation (CBD) studies (7,12,19). CBD leads to hypoventilation during eupnea and exercise and to a reduction in CO 2 sensitivity.…”

“…CBD leads to hypoventilation during eupnea and exercise and to a reduction in CO 2 sensitivity. However, in most species resting arterial PCO 2 (Pa CO 2 ) and CO 2 sensitivity return to pre-CBD levels within weeks after CBD, indicating that there is plasticity within this system (7).…”

Neural Control of Respiration by the Retrotrapezoid Nucleus.

“…Given the apparent absence of plasticity of CO 2 -responsive central chemoreceptors (rats, this study), a slight change in CB sensory transduction could also in theory explain why CBD produces such a long-lasting hypoventilation and rise in PCO 2 set point in large species and not in rats (Forster, 2003;Miller et al, 2013;Angelova et al, 2015). A major species difference in the central circuitry underlying the chemoreflexes need not be invoked to explain these observations.…”

“…Therefore, collateral damage to structures other than the carotid bodies may also contribute to the breathing changes. In fact, the return to normal ventilation and PCO 2 seems poorly correlated with the recovery of a ventilatory reflex to cyanide or hypoxia (Forster, 2003;Hodges et al, 2005;Mouradian et al, 2012). This discrepancy implies that some form of central plasticity of the respiratory network unrelated to oxygen sensing develops.…”