The Critical Role of the Central Autonomic Nervous System in Fetal-Neonatal Transition

Abstract

The objective of this article is to understand the complex role of the central autonomic nervous system in normal and complicated fetal-neonatal transition and how autonomic nervous system dysfunction can lead to brain injury. The central autonomic nervous system supports coordinated fetal transitional cardiovascular, respiratory, and endocrine responses to provide safe transition of the fetus at delivery. Fetal and maternal medical and environmental exposures can disrupt normal maturation of the autonomic nervous system in utero, cause dysfunction, and complicate fetal-neonatal transition. Brain injury may both be caused by autonomic nervous system failure and contribute directly to autonomic nervous system dysfunction in the fetus and newborn. The central autonomic nervous system has multiple roles in supporting transition of the fetus. Future studies should aim to improve real-time monitoring of fetal autonomic nervous system function and in supporting typical autonomic nervous system development even under complicated conditions.

Figure 1.. Brain stem cardiovascular (A) and respiratory (B) autonomic nervous system (ANS) centers.

(A) Sympathetic and parasympathetic control centers in the medulla provide ANS mediated control of the cardiovascular system. The nucleus tractus solitarius (NTS) is a key regulator of sympathetic and parasympathetic functions and controls cardiovascular and respiratory system functions. It receives peripheral afferent input from peripheral chemoreceptors and pulmonary mechanoreceptors. The cells of the NTS then modulate sympathetic and parasympathetic tone at the other brain stem centers (rostal ventrolateral medulla, caudal ventrolateral medulla, nucleus ambiguus, and dorsal motor nucleus of the vagus. (B) In the brain stem is a complex system for respiratory control that is influenced by the ANS. Central pattern generators involved in respiratory function produce rhythmic respiratory motor response based on afferent input. Major central pattern generator neuron groups consists of the pontine respiratory group, Bötzinger complex (expiratory rhythm generator), pre-Bötzinger complex (inspiratory rhythm generator), retrotrapezoid nucleus, the rostral ventral respiratory group (inspiratory), and the caudal ventral respiratory group (expiratory). The NTS, in the dorsal medulla, receives peripheral input that then modulates respiratory rhythmogenesis in the central pattern generators. The raphe nuclei are serotonergic neurons located within the medulla that project to multiple brain stem respiratory centers including the central pattern generators, Bötzinger and pre-Bötzinger complexes, as well as the phrenic motor nucleus, hypoglossal nerve, and others.

Figure 1.. Brain stem cardiovascular (A) and respiratory (B) autonomic nervous system (ANS) centers.

(A) Sympathetic and parasympathetic control centers in the medulla provide ANS mediated control of the cardiovascular system. The nucleus tractus solitarius (NTS) is a key regulator of sympathetic and parasympathetic functions and controls cardiovascular and respiratory system functions. It receives peripheral afferent input from peripheral chemoreceptors and pulmonary mechanoreceptors. The cells of the NTS then modulate sympathetic and parasympathetic tone at the other brain stem centers (rostal ventrolateral medulla, caudal ventrolateral medulla, nucleus ambiguus, and dorsal motor nucleus of the vagus. (B) In the brain stem is a complex system for respiratory control that is influenced by the ANS. Central pattern generators involved in respiratory function produce rhythmic respiratory motor response based on afferent input. Major central pattern generator neuron groups consists of the pontine respiratory group, Bötzinger complex (expiratory rhythm generator), pre-Bötzinger complex (inspiratory rhythm generator), retrotrapezoid nucleus, the rostral ventral respiratory group (inspiratory), and the caudal ventral respiratory group (expiratory). The NTS, in the dorsal medulla, receives peripheral input that then modulates respiratory rhythmogenesis in the central pattern generators. The raphe nuclei are serotonergic neurons located within the medulla that project to multiple brain stem respiratory centers including the central pattern generators, Bötzinger and pre-Bötzinger complexes, as well as the phrenic motor nucleus, hypoglossal nerve, and others.