Editorial: Neuronal Co-transmission

Neuronal Co-transmissionNeuronal co-transmission is now well-established as an aspect of nervous system function.However, this was not always the case, and acceptance of this important principle has required extensive work in a range of invertebrate and vertebrate systems (see Svensson et al. for a historical perspective).This work is reviewed in articles in this research topic, which we highlight in this Editorial.A common principle highlighted by several articles in this research topic is that neuropeptides stored in dense core vesicles (DCVs) are co-localized with amines, and also with "classical" small molecule neurotransmitters stored in small synaptic vesicles in single terminals (SSVs; see Cropper et al.; Hökfelt et al.; Merighi; Nässel; Trudeau and El Mestikawy; Svensson et al.). SSVs can co-store and co-release protons and ATP, which can also elicit postsynaptic responses (Soto et al.; Svensson et al.). Soto et al. show that changes in extracellular pH activate acid sensing ion channels, and they discuss whether this is a synaptically-restricted signal or a volume modulator of neuron excitability.Co-transmission in invertebrate neuronal circuits is highlighted by Nässel, Cropper et al., and Svensson et al.. Nässel summarizes the co-localization of neuropeptides and small molecule transmitters in Drosophila neuroendocrine cells, interneurons, and sensory and motor neurons, in circuits that influence learning and memory, circadian rhythms, and sensory, reproductive, developmental, and homeostatic functions.The circuit-related action of neuropeptides has been characterized in feeding circuits in the decapod crustacean stomatogastric ganglion (see the detailed discussion in Svensson et al.) and the Aplysia californica buccal ganglia (Cropper et al.).In Aplysia, analysis of the postsynaptic consequences of parallel neuropeptide actions has generated novel insights into the combinatorial effects of neuromodulators (Cropper et al.).Cropper et al. also address the role of different presynaptic activity patterns in the release of neuropeptides, an important aspect required for understanding the endogenous release of co-localized transmitters.Neuronal co-transmission has also been studied in vertebrate spinal circuits, both in dorsal horn sensory pathways and in spinal circuits involved in locomotion (see Svensson et al.).The mammalian peripheral nervous system has been an important preparation for studying cotransmission in relation to autonomic responses, and it provided some of the key early physiological evidence for co-localization (Burnstock, 1976; see Svensson et al.).For example, in sympathetic neurons in the rat superior cervical ganglion acetylcholine and GABA are found in the same neurons, albeit segregated into different axonal varicosities (this has been defined as co-existence

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