The Onset of the Fetal Respiratory Rhythm: An Emergent Property Triggered by Chemosensory Drive?

Abstract

The mechanisms responsible for the onset of respiratory activity during fetal life are unknown. The onset of respiratory rhythm may be a consequence of the genetic program of each of the constituents of the respiratory network, so they start to interact and generate respiratory cycles when reaching a certain degree of maturation. Alternatively, generation of cycles might require the contribution of recently formed sensory inputs that will trigger oscillatory activity in the nascent respiratory neural network. If this hypothesis is true, then sensory input to the respiratory generator must be already formed and become functional before the onset of fetal respiration. In this review, we evaluate the timing of the onset of the respiratory rhythm in comparison to the appearance of receptors, neurotransmitter machinery, and afferent projections provided by two central chemoreceptive nuclei, the raphe and locus coeruleus nuclei.

Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader–Willi syndrome

“…Conversely, the morphology and architecture of neurons in the surrounding medullary structures that provided a conditioning synaptic input to the pre-BötC neurons were abnormal; these neurons included enlarged and abnormally oriented serotonergic neurons and aberrant noradrenergic neurons [10]. During ontogeny, central chemoreception is necessary for respiratory rhythm stimulation [47]; hence, the abnormal serotonergic and noradrenergic neurons possibly corresponded to the abnormalities of the pre-BötC neuronal activity and respiratory drive in necdin-deficient mice. Reportedly, the morphology and activity of brainstem serotonergic neurons are aberrant in necdin-deficient mice, possibly induced by an increase in serotonin transporter [11,12].…”

Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader–Willi syndrome

“…Conversely, the morphology and architecture of neurons in the surrounding medullary structures that provided a conditioning synaptic input to the pre-BötC neurons were abnormal; these neurons included enlarged and abnormally oriented serotonergic neurons and aberrant noradrenergic neurons (10). During ontogeny, central chemoreception is necessary for respiratory rhythm stimulation (47); hence, the abnormal serotonergic and noradrenergic neurons possibly corresponded to the abnormalities of the pre-BötC neuronal activity and respiratory drive in necdin-de cient mice. Reportedly, the morphology and activity of brainstem serotonergic neurons are aberrant in necdin-de cient mice, possibly induced by an increase in serotonin transporter (11,12).…”

Maturation of Breathing‐Related Inhibitory Neurotransmission in the Medulla Oblongata of the Embryonic and Perinatal Zebra Finch (Taeniopygia guttata)

“…Second, it is of interest to understand how early rhythms are controlled and maintained during embryonic development. For example, how are early breathing rhythms embryologically initiated, and when, has not been settled from a phylotypic point of view and has only been thoroughly examined in rodents (Eugenín et al, ; Darnall, ; Beltrán‐Castillo et al, ). Third, data suggest that chloride conductance plays an important role in maintaining early excitability of the large scale depolarization waves in the developing CNS, and this depolarizing current can be strengthen when activity is pharmacological reduced, suggesting a form of developmental plasticity that may be critical for proper circuit construction.…”

“…Nevertheless, studies investigating the ontogeny of respiratory motor output, especially those details that precede the appearance of aerial breathing behaviors, have been relatively uncommon and are limited by technical details associated with placentation and viviparity in mammals. Where data do exist studies have concentrated on the perinatal period in rats and mice (>60% of gestational term), because data show that the embryonic parafacial region and preBötzinger complex are established during this period (Pagliardini et al, ; Thoby‐Brisson et al, ; Eugenín et al, ; Fortin and Thoby‐Brisson, and for a recent review see Beltrán‐Castillo et al, ). Accordingly, we know little about the ontogeny of breathing motor rhythms, except for the final week of rodent gestation, which is analogous to the third trimester in the human fetus, a chronological period that is significantly later than the period in which the onset of breathing motor rhythms begin in other mammals.…”