Neonatal maturation of the hypercapnic ventilatory response and central neural CO2 chemosensitivity

Abstract

The ventilatory response to CO 2 changes as a function of neonatal development. In rats, a ventilatory response to CO 2 is present in the first 5 days of life, but this ventilatory response to CO 2 wanes and reaches its lowest point around postnatal day 8. Subsequently, the ventilatory response to CO 2 rises towards adult levels. Similar patterns in the ventilatory response to CO 2 are seen in some other species, although some animals do not exhibit all of these phases. Different developmental patterns of the ventilatory response to CO 2 may be related to the state of development of the animal at birth. The triphasic pattern of responsiveness (early decline, a nadir, and subsequent achievement of adult levels of responsiveness) may arise from the development of several processes, including central neural mechanisms, gas exchange, the neuromuscular junction, respiratory muscles and respiratory mechanics. We only discuss central neural mechanisms here, including altered CO 2 sensitivity of neurons among the various sites of central CO 2 chemosensitivity, changes in astrocytic function during development, the maturation of electrical and chemical synaptic mechanisms (both inhibitory and excitatory mechanisms) or changes in the integration of chemosensory information originating from peripheral and multiple central CO 2 chemosensory sites. Among these central processes, the maturation of synaptic mechanisms seems most important and the relative maturation of synaptic processes may also determine how plastic the response to CO 2 is at any particular age.

GFP-expressing locus ceruleus neurons from Prp57 transgenic mice exhibit CO2/H+ responses in primary cell culture

“…One possibility is that LC neurons studied in cell culture are older than those studied in slices, since this leads to larger responses in raphé neurons (see below). However, others have not found a significant effect of age on chemosensitivity of LC neurons (47,63), and we did not find a significant effect of age on the response of LC neurons in culture after P12 (Fig. 9).…”

Heart Rate Variability and Hypercapnia in Duchenne Muscular Dystrophy

“…Hypercapnia is well known to increase respiratory neuron firings in the brainstem (15,16) and then increase the respiratory rate and volume (14,15) as well as a reduction of parasympathetic activity (17). Based on these studies (14)(15)(16)(17), hypercapnia would decrease the parasympathetic nervous system activity and CVrr. In fact, in an animal study, hypercapnia decreased "high frequency" heart rate variability (8) [i.e.…”

Prenatal nicotine exposure increases hyperventilation in α4-knock-out mice during mild asphyxia

“…Further, the ␣4 receptor modulates excitatory control in the carotid body through the release of adenosine (Conde and Monteiro, 2006) and in the brainstem, inhibitory control through dopaminergic and GABAergic release (Klink et al, 2001;Marubio et al, 2003;Ross et al, 2000). In rats and mice the hypoxic ventilatory response which is immature at birth undergoes rapid development within the first week of life Carroll et al, 1993) whereas the response to CO 2 of central chemoreceptors wanes at this time (Putnam et al, 2005;Stunden et al, 2001). Thus it may be that in the absence of ␣4-containing receptors, nicotine actually enhances the central chemoreflex response to MA via alterations in GABAergic or dopaminergic control of breathing.…”