Regulating peptidergic modulation of rhythmically active neural circuits

The ability of neuropeptides to modulate neural circuit activity is well established, but little is known regarding how the actions of neurally-released peptides are regulated. This issue is being studied in the isolated stomatogastric nervous system (STNS) of decapod crustaceans. The STNS is a small neural system that contains the rhythmically active gastric mill (chewing) and pyloric (filtering of chewed food) motor circuits within the stomatogastric ganglion (STG). These circuits are influenced by a set of modulatory projection neurons in the neighboring commissural and oesophageal ganglia. This system includes three different projection neurons that contain the peptide transmitter proctolin among an overlapping complement of cotransmitters. Despite their shared proctolinergic phenotype, when these projection neurons are activated individually each of them has distinct actions on the gastric mill and pyloric circuits. These distinct actions result only partly from the presence of different cotransmitters in these projection neurons. Also contributing to these distinct actions are differences in the pattern of transmitter release as well as a differential, peptidase-mediated sculpting of the actions of the proctolin released from each projection neuron. There is also a convergence of peptide cotransmitter actions, at the level of the target ion channel, which might limit the effectiveness of each individual cotransmitter. One lesson already learned from this small neural system is that there is a diverse collection of regulatory mechanisms for controlling the actions of neurally-released peptides on rhythmically active neural circuits.