BREATHING: Rhythmicity, Plasticity, Chemosensitivity

Abstract

Breathing is a vital behavior that is particularly amenable to experimental investigation. We review recent progress on three problems of broad interest. (i) Where and how is respiratory rhythm generated? The preBötzinger Complex is a critical site, whereas pacemaker neurons may not be essential. The possibility that coupled oscillators are involved is considered. (ii) What are the mechanisms that underlie the plasticity necessary for adaptive changes in breathing? Serotonin-dependent long-term facilitation following intermittent hypoxia is an important example of such plasticity, and a model that can account for this adaptive behavior is discussed. (iii) Where and how are the regulated variables CO2 and pH sensed? These sensors are essential if breathing is to be appropriate for metabolism. Neurons with appropriate chemosensitivity are spread throughout the brainstem; their individual properties and collective role are just beginning to be understood.

Focal acidosis in the pre-Bötzinger complex area of awake goats induces a mild tachypnea

“…Second, a FA in the preBötzC does not elicit nonrespiratory effects, whereas a FA in the MRN (10,11) or CFN (17) results in significant changes in V O 2 , MABP, or HR. These first two unique effects seem consistent with the important role of the preBötzC in respiratory rhythm generation (4,19,23,29,30,37). Third, bilateral FA with 25 and 50% CO 2 in the preBötzC does not elicit any consistent or significant ventilatory response, whereas bilateral FA in the MRN elicits a greater response than a unilateral FA (10,11).…”

“…Nattie et al (4,20,21) have proposed that chemoreceptors at widespread sites are needed to serve different physiological functions. For example, data from their studies suggest the effect on breathing and other physiological functions is state dependent (4,20,21).…”

“…Nattie et al (4,20,21) have proposed that chemoreceptors at widespread sites are needed to serve different physiological functions. For example, data from their studies suggest the effect on breathing and other physiological functions is state dependent (4,20,21). The key findings from this study are as follows: 1) during global acidosis, ECF pH does not change the same in the preBö tzC as previously found in the MRN; and 2) the ventilatory and overall physiological responses to FA in the preBö tzC are not qualitatively or quantitatively the same as previously shown for other brain sites.…”

“…This relatively small response to FA might, in part, be due to alkalosis at other chemosensitive sites during FA at one or a few sites. Accordingly, it is conceivable that the hyperpnea during global brain acidosis reflects the cumulative or additive effect of chemoreception at multiple sites, rather than a result of activation of chemoreceptors at any single site.The preBötzC, a medullary area hypothesized to be the dominant inspiratory rhythm generator (4,19,23,29,30,37), may also contain neurons that exhibit CO 2 /H ϩ sensitivity. Notably, an acetazolamide-induced acidosis in the preBötzC of anesthetized, vagotomized, paralyzed, and mechanically ventilated cats increases the frequency and amplitude of phrenic nerve activity (31, 32).…”

“…The preBötzC, a medullary area hypothesized to be the dominant inspiratory rhythm generator (4,19,23,29,30,37), may also contain neurons that exhibit CO 2 /H ϩ sensitivity. Notably, an acetazolamide-induced acidosis in the preBötzC of anesthetized, vagotomized, paralyzed, and mechanically ventilated cats increases the frequency and amplitude of phrenic nerve activity (31,32).…”