Peptide Cotransmitters as Dynamic, Intrinsic Modulators of Network Activity

Abstract

Neurons can contain both neuropeptides and “classic” small molecule transmitters. Much progress has been made in studies designed to determine the functional significance of this arrangement in experiments conducted in invertebrates and in the vertebrate autonomic nervous system. In this review article, we describe some of this research. In particular, we review early studies that related peptide release to physiological firing patterns of neurons. Additionally, we discuss more recent experiments informed by this early work that have sought to determine the functional significance of peptide cotransmission in the situation where peptides are released from neurons that are part of (i.e., are intrinsic to) a behavior generating circuit in the CNS. In this situation, peptide release will presumably be tightly coupled to the manner in which a network is activated. For example, data obtained in early studies suggest that peptide release will be potentiated when behavior is executed rapidly and intervals between periods of neural activity are relatively short. Further, early studies demonstrated that when neural activity is maintained, there are progressive changes (e.g., increases) in the amount of peptide that is released (even in the absence of a change in neural activity). This suggests that intrinsic peptidergic modulators in the CNS are likely to exert effects that are manifested dynamically in an activity-dependent manner. This type of modulation is likely to differ markedly from the modulation that occurs when a peptide hormone is present at a relatively fixed concentration in the blood.

Multiple Origins of Neurons From Secretory Cells

“…What is a neuron? As their “ancestors,” all modern neurons are polarized secretory cells specialized for directional active conducting and release of more than one transmitter : usually 2–5 peptides and a low-molecular transmitter(s) (Weiss et al, 1992 ; Moroz et al, 2005 , 2006 ; Moroz and Kohn, 2010 ; Cropper et al, 2018 ; Merighi, 2018 ; Nassel, 2018 ; Svensson et al, 2018 ). These features enable neurons to convey signals, primarily chemical, beyond their immediate neighbors and without affecting all intervening cells en route .…”

Similarities and differences in circuit responses to applied Gly1-SIFamide and peptidergic (Gly1-SIFamide) neuron stimulation

“…Despite the fact that neuronally released peptide often acts in a paracrine manner, its actions are not always well mimicked by the aforementioned approaches ). Yet there are only a small number of identified peptidergic neurons with elucidated circuit actions (e.g., Blitz et al 1999;Wood et al 2000;Chalasani et al 2010;Kwiatkowski et al 2013;Qiu et al 2016;Clark et al 2018;Cropper et al 2018b).…”

Persistent effects of cyclic adenosine monophosphate are directly responsible for maintaining a neural network state

“…We study the network that mediates feeding behavior in the mollusc Aplysia . This network is like many others in that its activity is configured and reconfigured by modulatory neurotransmitters to generate ingestive and egestive motor programs 10 . These experiments focus on ingestive activity.…”