Feeding state-specific hormonal tuning of neural circuit modulation

Studies of hormone influences on neural circuits and behavior have primarily focused on the manipulation of individual hormones. Here, we examine the influence of behavioral (feeding) state-specific hormonal environments on the gastric mill (chewing) circuit configured by the neuropeptide Gly¹-SIFamide (G-SIFamide) in the isolated Cancer borealis stomatogastric ganglion (STG). The G-SIFamide-activated gastric mill rhythm, which is similar to that driven by the G-SIFamidergic projection neuron modulatory commissural neuron 5 (MCN5), is distinguished from other gastric mill rhythms by the presence of rhythmic, prolonged inferior cardiac (IC) neuron bursts and associated interruptions of the pyloric rhythm. Applying 1 µM G-SIFamide in saline only occasionally activated the gastric mill rhythm, whereas this rhythm occurred more frequently when 1 µM G-SIFamide was applied in hemolymph from an unfed crab and even more often in 1-h postfed hemolymph. No novel gastric mill neuron activity occurred under these latter conditions, suggesting that hemolymph strengthened the G-SIFamide actions. Supporting this suggestion, 10 µM G-SIFamide in saline elicited this rhythm as frequently as 1 µM G-SIFamide in unfed hemolymph. Moreover, any G-SIFamide application following an initial application of 1 µM G-SIFamide in hemolymph (unfed or fed) or 10 µM G-SIFamide in saline, but not 1 µM G-SIFamide in saline, activated the gastric mill rhythm less frequently. Mass spectrometry analysis indicated that the hemolymph influence was unlikely due to additional G-SIFamide, because no SIFamide peptide family members were identified in either hemolymph. These results suggest that one or more non-SIFamide hormones strengthen this neuropeptide-modulated circuit output by increasing the effectiveness of the applied G-SIFamide.NEW & NOTEWORTHY We establish that a complete, natural hormonal environment (hemolymph) increases the likelihood of a neuropeptide activating the gastric mill (chewing) rhythm in the crab stomatogastric ganglion (STG). The similar action of a higher neuropeptide concentration in saline, its comparable desensitizing effect to that of neuropeptide plus hemolymph on subsequent neuropeptide applications, and the absence of that neuropeptide in hemolymph suggest one or more distinct hormones act to enhance the effectiveness of the applied peptide.