Cnidarian chemical neurotransmission, an updated overview

Abstract

The ultrastructural, histochemical, immunocytochemical, biochemical, molecular, behavioral and physiological evidence for non-peptidergic and peptidergic chemical neurotransmission in the Anthozoa, Hydrozoa, Scyphozoa and Cubozoa is surveyed. With the possible exception of data for the catecholamines and peptides in some animals, the set of cumulative data – the evidence from all methodologies – is incomplete. Taken together, the evidence from all experimental approaches suggests that both classical fast (acetylcholine, glutamate, GABA, glycine) and slow (catecholamines and serotonin) transmitters, as well as neuropeptides, are involved in cnidarian neurotransmission. Ultrastructural evidence for peptidergic, serotonergic, and catecholaminergic synaptic localization is available, but the presence of clear and dense-cored synaptic vesicles also suggests both fast and slow classical transmission. Immunocytochemical studies, in general, reveal a continuous, non-localized distribution of neuropeptides, suggesting a neuromodulatory role for them. Immunocytochemical and biochemical studies indicate the presence of glutamate, GABA, serotonin, catecholamines (and/or their receptors), RFamides, nitric oxide and eicosanoids in cnidarian neurons and tissues. Gene sequences for peptidergic preprohormones have been reported; putative gene homologies to receptor proteins for vertebrate transmitters have been found in Hydra. Behavioral and physiological studies implicate classical transmitters, neuropeptides, eicosanoids and nitric oxide in the coordination of the neuroeffector systems.

Introduction

Cnidarians have occupied a unique place in the history, indeed, in the controversies, of biology and neurobiology. So, for example, Abraham Trembley, in the 18th Century, wasn't at all sure whether the small flower-like object he discovered in the pond was a plant or an animal (Trembley, 1744). It was only hydra's animated behavior, contracting and stretching when it was touched, that prompted Trembley to classify it among the Animalia. Two centuries later, despite extensive histochemical documentation of nerve nets in coelenterates (Bullock and Horridge, 1965), the absence of recognizable synapses led some workers to question the very existence of nerves in Hydra (see discussion in Lenhoff and Loomis, 1961). The subsequent discovery of epithelial conduction in hydromedusae (Mackie and Passano, 1968) further contributed to the uncertain status of coelenterate neurons (Spencer and Schwab, 1982). However, when Westfall and co-workers (Westfall, 1970a, Westfall, 1970b, Westfall, 1973a, Westfall, 1973b, Westfall, 1996, Westfall et al., 1971) described synaptic vesicles in sea anemones and Hydra, doubts of the existence of a cnidarian nervous system were erased. The question now became what sort of neurotransmitters do cnidarian synapses use. That question, the nature of cnidarian neurotransmitters, continues to absorb coelenterate neurobiologists to this day.

Early histochemical, regeneration, and behavioral studies gave evidence that classical vertebrate transmitters such as acetylcholine, norephinephrine, serotonin and histamine were involved in coordinating morphogenesis and behavior (Lentz and Barrnett, 1961, Lentz and Barrnett, 1962a, Lentz and Barrnett, 1962b, Lentz and Barrnett, 1963, Singer, 1964, Wood and Lentz, 1964, Lentz, 1966, for review; Kass-Simon, 1976, Kass-Simon and Passano, 1978). However, proof, by Paton's criteria (1958), that these substances were actual neurotransmitters, was difficult to obtain. A failure to extract classical transmitters from various species or to demonstrate their presence in synaptic vesicles (Anderson and Spencer, 1989), along with an inability to identify the appropriate metabolic enzymes, or to demonstrate synaptic release, called into question the existence of classical chemical transmitters in the Cnidaria (Martin and Spencer, 1983). This, together with the compelling radioimmunographic demonstrations that a very large, but selective number of peptides and neuropeptides were contained in the cnidarian nervous system (Grimmelikhuijzen, 1984, Grimmelikhuijzen et al., 1989, for reviews) led to the often-voiced opinion that “many of the ‘fast’ transmitters such as glutamate, acetylcholine, γ-aminobutyric acid (GABA) and glycine, appear to be absent in cnidarians” (Grimmelikhuijzen et al., 2002, p. 1700).

However, evidence continues to accumulate that both peptidergic and non-peptidergic neurotransmission/neuromodulation is fundamental to cnidarian physiology, and the possibility has even been raised that peptides of the RFamide family may act as transmitters in one species (Anthozoa) and as neuromodulators in another (Hydrozoa) (Spencer, 1991). It should be noted that the criteria that distinguish neurotransmitters from neuromodulators have not been definitively stated — either for mammalian systems (cf. Krieger, 1983), or for the Cnidaria. Further, the discovery in the 1970's of the coexistence of peptides and classical transmitters in the same neuron – contrary to the previous dogma of one transmitter, one neuron, referred to as Dale's principle (Eccles, 1957) – has for some time fundamentally transformed the characterization of synaptic transmission. Rather than attempt to distinguish between neurotransmission and neuromodulation, this review is aimed at surveying the anatomical, biochemical, molecular, and physiological evidence for the participation of various chemical substances in the intercellular communication in cnidarian neuroeffector systems.