Colocalization and Cotransmission of Classical Neurotransmitters: An Invertebrate Perspective

Abstract

Once considered a curiosity, the notion that individual neurons can contain more than one classical neurotransmitter has gained increasing credibility in recent years. Several contributions to the growing recognition of classical neurotransmitter colocalization and cotransmission originate from studies using invertebrate nervous systems. Some of these model systems contain large identified neurons that contribute to well-understood circuits and networks. They therefore enable investigators to pose questions that are presently beyond the technical limitations of experimental approaches to mammalian brain function. This chapter reviews our current understanding of classical neurotransmitter colocalization and cotransmission in invertebrates. It focuses on identified neurons that could enable assessment of cotransmitter contributions to synaptic signals and neural network function. Major gaps in our present conception of classical neurotransmitter colocalization and cotransmission are emphasized, with an aim toward stimulating further study of their physiological and functional consequences.

GABA‐like immunoreactivity in Biomphalaria: Colocalization with tyrosine hydroxylase‐like immunoreactivity in the feeding motor systems of panpulmonate snails

“…Increasing evidence supports the hypothesis that classical neurotransmitters can be colocalized in individual neurons (Borisovska & Westbrook, ; Gutíerrez, ; Seal & Edwards, ; Vaaga, Borisovska, & Westbrook, ). One such combination, γ–aminobutyric acid (GABA) with dopamine (DA), has been reported in several cell types within vertebrate nervous systems, including periglomerular cells of the mouse olfactory bulb (Borisovska, Bensen, Chong, & Westbrook, ; Liu, Plachez, Shao, Puche, & Shipley, ; Maher & Westbrook, ), retinal amacrine cells (Hirasawa, Contini, & Raviola, ; Hirasawa, Puopolo, & Raviola, ), mouse nigrostriatal and ventral tegmental cells (Tritsch, Ding, & Sabatini, ; Tritsch, Granger, & Sabatini, ; Trudeau et al, ), nerve terminals of the Xenopus laevis pituitary (de Rijk, van Strien, & Roubos, ), and neurons in the spinal cord of the sea lamprey (Barreiro‐Iglesias, Villar‐Cerviño, Anadón, & Rodicio, ).…”

“…The recent localization of GABAli in the buccal ganglia of Nudipleura (Gunaratne & Katz, ) sets the stage for exploring whether GABA‐DA colocalization predated divergence of the Tectipleura and Nudipleura groups. This avenue of investigation should provide opportunities to explore the functional consequences of classical neurotransmitter colocalization in identified neurons and tractable motor networks (Miller, ). This approach should also inform our understanding of cotransmission by classical neurotransmitters in more complex vertebrate nervous systems.…”

“…It has been proposed the simpler nervous systems of certain invertebrates can provide opportunities to further examine colocalized classical neurotransmitters in the context of identified neurons and defined neural circuits (Miller, ). In gastropod molluscs, a neurotransmitter role for GABA was initially suggested by pharmacological studies in which it was found to produce both excitatory and inhibitory responses upon application to snail neurons (Gerschenfeld & Tauc, ; Walker, Crossman, Woodruff, & Kerkut, ; Walker, Aranza, Kerkut, & Woodruff, ).…”

Classical Neurotransmitters and Neuropeptides

“…This was in line with early evidence for multiple transmitters in isolated (large) invertebrate neurons. 22,31 Moreover, results from mononeuron cultures 10 showed a developmental switch in autonomic neurons from a noradrenergic to a cholinergic phenotype with a transient synthesis and release both NA and ACh. A further type of transmission was termed NANC (nonadrenergic, noncholinergic), the prime transmitter candidate being ATP, so called purinergic transmission with corelease of NA [see Ref.…”