About this Research Topic
Understanding the functional consequences of neurotransmitter co-localization and co-transmission is an important topic in neuroscience, and interest in this area is growing. However, the complexity of co-transmission makes it challenging to elucidate, as does the need to study it from the subcellular to behavioral levels. The vast number of neurotransmitters and the ability of each to have multiple actions by binding to different ionotropic and metabotropic receptors, influencing multiple ion channel types, create complex chemical networks that continuously tune and regulate neuronal circuits to make the behaviors they influence adaptable and flexible. Functional and behavioral roles of co-transmission have traditionally been studied in invertebrates and peripheral vertebrate nervous systems using traditional electrophysiological and molecular genetic methods. As will be evident in some articles in this research topic, today’s methodological possibilities (e.g. optogenetics) have improved the opportunity to investigate co-transmission in the mammalian CNS.
A range of different combinations of neurotransmitter co-localizations have been described. For example, small molecule transmitters such as glutamate, acetylcholine, GABA, ATP and glycine that activate ionotropic (as well as metabotropic) receptors are commonly co-localized and co-released with one another as well as with slower acting aminergic (e.g. dopamine, serotonin, and noradrenaline/octopamine) and/or peptidergic transmitters whose actions can modulate cellular and synaptic dynamics, the properties of circuits, and the behaviors these circuits control. In this research topic we aim to highlight how co-transmission complicates simplistic pharmacological approaches, due in part to functional interactions between transmitters. In particular, how the spatial and temporal release of co-transmitters collectively influences circuit(s) is mostly unresolved.
As part of this effort, we aim to consider the pre-synaptic dynamics that differentiate the release of co-transmitters. After the discovery of co-transmission in the late 1970’s/early 1980’s, it was assumed that neurons co-store and co-release the same set of neurotransmitters at all their varicosities. However, evidence has accumulated to reveal that neurotransmitters can be stored and released independently, and at distinct terminals of single neurons. These findings challenge the assumption of co-packaging, and support the hypothesis that neurons can differentially sort or segregate their neurotransmitters to independent release sites. We will thus aim to discuss the consequences that result from co-transmitter segregation.
Functional consequences of co-transmission
As many aminergic and neuropeptidergic CNS neurons co-localize small molecule transmitters, and many of these systems are implicated in neurological disorders, this Research Topic also has potential clinical relevance. For example, Ventral Tegmental Area neurons involved in disorders such as drug abuse appear to segregate glutamate and dopamine into different subcellular compartments within single axons in their target area, the Nucleus Accumbens. Similarly, individual serotonergic Raphe Nuclei neurons, which are implicated in depressive disorders can segregate serotonin and glutamate to separate axon terminals.
Thus, we will provide a broad approach to the subject of co-transmission and its impact on neuronal circuits and behavior. We will include research performed in invertebrate and vertebrate (both non-mammalian and mammalian) neuronal circuits, with the ultimate goal of establishing general principles regarding co-transmission that span multiple animal models and functional circuits.
Keywords: co-transmission, plasticity, synaptic, sorting, release
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