AUTHOR=Svensson Erik , Apergis-Schoute John , Burnstock Geoffrey , Nusbaum Michael P. , Parker David , Schiöth Helgi B. TITLE=General Principles of Neuronal Co-transmission: Insights From Multiple Model Systems JOURNAL=Frontiers in Neural Circuits VOLUME=12 YEAR=2019 URL=https://www.frontiersin.org/journals/neural-circuits/articles/10.3389/fncir.2018.00117 DOI=10.3389/fncir.2018.00117 ISSN=1662-5110 ABSTRACT=

It is now accepted that neurons contain and release multiple transmitter substances. However, we still have only limited insight into the regulation and functional effects of this co-transmission. Given that there are 200 or more neurotransmitters, the chemical complexity of the nervous system is daunting. This is made more-so by the fact that their interacting effects can generate diverse non-linear and novel consequences. The relatively poor history of pharmacological approaches likely reflects the fact that manipulating a transmitter system will not necessarily mimic its roles within the normal chemical environment of the nervous system (e.g., when it acts in parallel with co-transmitters). In this article, co-transmission is discussed in a range of systems [from invertebrate and lower vertebrate models, up to the mammalian peripheral and central nervous system (CNS)] to highlight approaches used, degree of understanding, and open questions and future directions. Finally, we offer some outlines of what we consider to be the general principles of co-transmission, as well as what we think are the most pressing general aspects that need to be addressed to move forward in our understanding of co-transmission.