Neuronal Mechanisms of Oxygen Chemoreception: An Invertebrate Perspective

Abstract

Since the evolution of aerobic metabolism, cellular requirements for molecular oxygen have been the major driver for the development of sophisticated mechanisms underlying both invertebrate and vertebrate respiratory behaviour. Among the most important characteristics of respiration is its adaptability, which allows animals to maintain oxygen homeostasis over a wide range of environmental and metabolic conditions. In all animals, the respiratory behaviour is controlled by neural networks often termed respiratory central pattern generators (rCPG). While rCPG neurons are intrinsically capable of generating rhythmical outputs, the respiratory needs are generally "sensed" by either central or peripheral chemoreceptive neurons. The mechanisms by which chemoreceptors respond to changes in oxygen and modulate central respiratory control centers have been the focus of decades of research. However, our understanding of these mechanisms has been limited due to an inability to precisely locate oxygen chemoreceptor populations, combined with the overwhelming complexity of vertebrate neural circuits. Although mammalian models remain the gold standard for research in general, invertebrates do nevertheless offer greatly simplified neural networks that share fundamental similarities with vertebrates. The following review will provide evidence for the existence of oxygen chemoreceptors in many invertebrate groups and reveal the mechanisms by which these neurons may "perceive" environmental oxygen and drive central rCPG activity. For this, we will specifically highlight an invertebrate model, the pond snail Lymnaea stagnalis whose episodic respiratory behaviour resembles that of diving mammals. The rCPG neurons have been identified and fully characterized in this model both in vivo and in vitro. The Lymnaea respiratory network has also been reconstructed in vitro and the contributions of individual rCPG neurons towards rhythm generation characterized through direct intracellular recordings. We now provide evidence for the presence of genuine peripheral oxygen chemoreceptors in Lymnaea, and demonstrate that these neurons respond to hypoxia in a manner analogous to that of mammalian carotid bodies. These chemoreceptor cells not only drive the activity of the rCPG neurons but their synaptic connections also exhibit hypoxia-induced plasticity. The lessons learned from this model will likely reveal fundamental principles underlying both peripheral and central respiratory control mechanisms, which may be conserved in both invertebrate and vertebrate species.

Graded hypoxia acts through a network of distributed peripheral oxygen chemoreceptors to produce changes in respiratory behaviour and plasticity

“…In addition, we described changes in the expression of respiratory behaviour that occurred during severe hypoxia (high F B , smaller pneumostome openings), and a clear hypoxic escape‐response (i.e. migration) that has been noted for many invertebrate (Janes & Syed, ) and vertebrate taxa (Bell & Eggleston, ; Ludsin et al ., ).…”

A Comparative Study of Cell Specific Effects of Systemic and Volatile Anesthetics on Identified Motor Neurons and Interneurons of Lymnaea stagnalis (L.), Both in the Isolated Brain and in Single Cell Culture

“…The rCPG also controls cardiac functions (Benjamin and Kemenes, 2013). RPeD1 projects directly to the osphradial ganglion and receives direct excitatory, monosynaptic, cholinergic inputs from osphradial neurons (Bell et al, 2007) which are responsive to hypoxia (Janes and Syed, 2012). The parietal A group neurons innervate the musculature of the mantle cavity, while the visceral J cells are pneumostome opener motor neurones and some pneumostome closer motor neurons are thought to be located within visceral M group (Moroz, 1991).…”

Uncovering the Cellular and Molecular Mechanisms of Synapse Formation and Functional Specificity Using Central Neurons of Lymnaea stagnalis

“…Note that the rhythmic pattern observed in vitro mimics the respiratory cycle observed in vivo. Figure adapted and modified with permission from Syed et al, and Janes and Syed …”

“…Using a combination of behavioral and electrophysiological approaches, we have recently reported that Lymnaea possesses a spatially distributed network of peripheral oxygen chemoreceptor sites that respond selectively to graded hypoxic challenges. 44,49 These findings suggest that the existence of multiple oxygen chemoreceptor sites is an evolutionarily conserved strategy that underlies the adaptability of respiratory behavior to meet changing environmental demands, and opens to new opportunities to investigate the fundamental synaptic mechanisms that regulate respiratory systems.…”