A Gonadotropin-Releasing Hormone-Like Molecule Modulates the Activity of Diverse Central Neurons in a Gastropod Mollusk, Aplysia Californica

Abstract

In vertebrates, gonadotropin-releasing hormone (GnRH) is a crucial decapeptide that activates the hypothalamic–pituitary–gonadal axis to ensure successful reproduction. Recently, a GnRH-like molecule has been isolated from a gastropod mollusk, Aplysia californica. This GnRH (ap-GnRH) is deduced to be an undecapeptide, and its function remains to be explored. Our previous study demonstrated that ap-GnRH did not stimulate a range of reproductive parameters. Instead, it affected acute behavioral and locomotive changes unrelated to reproduction. In this study, we used electrophysiology and retrograde tracing to further explore the central role of ap-GnRH. Sharp-electrode intracellular recordings revealed that ap-GnRH had diverse effects on central neurons that ranged from excitatory, inhibitory, to the alteration of membrane potential. Unexpectedly, extracellular recordings revealed that ap-GnRH suppressed the onset of electrical afterdischarge in bag cell neurons, suggesting an inhibitory effect on female reproduction. Lastly, using immunocytochemistry coupled with nickel backfill, we demonstrated that some ap-GnRH neurons projected to efferent nerves known to innervate the foot and parapodia, suggesting ap-GnRH may directly modulate the motor output of these peripheral tissues. Overall, our results suggested that in A. californica, ap-GnRH more likely functioned as a central modulator of complex behavior and motor regulation rather than as a conventional reproductive stimulator.

Functional Authentication of a Novel Gastropod Gonadotropin-Releasing Hormone Receptor Reveals Unusual Features and Evolutionary Insight

“…Orthologs of vertebrate GnRH have recently been discovered in protostomes, but their physiological roles are not clearly defined [ 3 – 5 ]. Physiological studies using native GnRH in molluscan models suggest protostome forms of GnRH have become highly diversified and are multi-functional molecules responsible for a wide range of regulation including neural control [ 6 ], motor activity [ 6 , 7 ], feeding [ 7 ], and reproduction [ 8 – 10 ]. Further, the presence of additional molecules that are orthologous to protostome GnRH, including adipokinetic hormone (AKH), corazonin (CRZ), and AKH/CRZ-related peptide (ACP), have been documented [ 11 , 12 ].…”

Identification, presence, and possible multifunctional regulatory role of invertebrate gonadotropin-releasing hormone/corazonin molecule in the great pond snail (Lymnaea stagnalis)

“…These finding can be confirmed in the future with physiological studies using purified or synthetic ly-GnRH/CRZ peptide. Our results further suggest the term "invGnRH" (e.g., oct-GnRH, ap-GnRH) should be revised to avoid the connotation that these peptides serve specialized reproductive function similar to vertebrate GnRHs (Iwakoshi et al, 2004;Minakata et al, 2009;Tsai et al, 2010;Sun and Tsai, 2011;Treen et al, 2012;Jung et al, 2014. Nagasawa et al, 2015Kavanaugh and Tsai, 2016).…”

“…In other words, invGnRH/CRZ molecules, initially named invGnRH (e.g., oct-GnRH, ap-GnRH), may not assume a specialized reproductive role as seen in vertebrate GnRH. Indeed, emerging evidence suggests diverse biological effects of invGnRH/CRZ that include not only reproductive, but also motor, behavioral, and neuromodulatory functions (Iwakoshi et al, 2004;Minakata et al, 2009;Tsai et al, 2010;Sun and Tsai, 2011;Treen et al, 2012;Jung et al, 2014. Nagasawa et al, 2015 Kavanaugh and Tsai, 2016).…”

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“…19 In Aplysia, it has been demonstrated that peptides released by the bag cells during and after discharge have a number of effects on the electrical activity of central neurons in vitro. 20 These peptides also affect gill and siphon contractions and the arterial system. Injections of these peptides into intact animals also induce behavioral changes.…”