Functional consequences of neuropeptide and small-molecule co-transmission

Abstract

Colocalization of small-molecule and neuropeptide transmitters is common throughout the nervous system of all animals. The resulting co-transmission, which provides conjoint ionotropic (‘classical’) and metabotropic (‘modulatory’) actions, includes neuropeptide-specific aspects that are qualitatively different from those that result from metabotropic actions of small-molecule transmitter release. Here, we focus on the flexibility afforded to microcircuits by such co-transmission, using examples from various nervous systems. Insights from such studies indicate that co-transmission mediated even by a single neuron can configure microcircuit activity via an array of contributing mechanisms, operating on multiple timescales, to enhance both behavioural flexibility and robustness.

Involvement of Neuropeptide Y in Post-Incisional Nociception in Rats

“…This could modulate the transmission of pain signals. Neuropeptides are inactivated by extracellular peptidases upon release apart from binding to their cognate receptors because in contrast to small molecule neurotransmitters, there are no reuptake mechanisms for the former [32,33]. An increase, thereafter, between 6 and 12 h was likely the result of re-synthesis of this neuropeptide.…”

Neurotransmission: peptide transmitters turn 36

“…However, prior to Jan and Jan's 1982 paper, these concepts were not yet fully established at the level of identified neurons and synapses. The fact that cotransmission, in particular, was already evident nearly four decades ago likely is surprising to some because, despite a smattering of subsequent studies (Adams and O'Shea, 1983;Sigvardt et al, 1986;Bishop et al, 1987;Whim and Lloyd, 1989;Kupfermann, 1991;Nusbaum et al, 2001), it has only been during the past 10 years or so that the functional consequences of co-transmission have become a growth industry (Vaaga et al, 2014;Nusbaum et al, 2017).…”

“…While this number of citations may not seem impressive by the standards of recent high-profile publications, the research community was considerably smaller in the 1980s. Moreover, this paper continues to be acknowledged today (in fact, 2016 was the first year since 1982 when it garnered no citations, but there will be at least two citations in 2017) as seminal to the now-burgeoning field of peptidergic (co)transmission, a process which is clearly integral to nervous system function in all animals (Nässel, 2009;van den Pol, 2012;Nusbaum et al, 2017).…”

“…This approach was especially challenging in the mammalian central nervous system (CNS) which, at that time, was not the friendly territory for synaptic physiologists that it has more recently become. The study of peptidergic transmission involving identified neurons is also vexing because the postsynaptic targets are not obvious, precisely because this type of transmission may lack the point-to-point synaptic contacts and precise postsynaptic potentials that are the hallmarks of 'classical' ionotropic synaptic transmission mediated by small molecule transmitters (Nässel, 2009;Nusbaum et al, 2017).…”

“…In comparison, there are still fewer than a dozen classical small molecule transmitters. Even the small stomatogastric ganglion (26 neurons plus ∼20 inputs) of the crab, Cancer borealis, contains at least 60 peptide (co)transmitters, many of which are known to modulate the motor circuits therein (Marder, 2012;Chen et al, 2014;Nusbaum et al, 2017). The seminal finding of transmission 'at a distance' has also stood the test of time and is now a general principle of peptidergic transmission, as is the co-localization of peptide and small molecule transmitters (van den Pol, 2012;Nusbaum et al, 2017).…”