Auto-inhibitory control of peptidergic molluscan neurons and reproductive senescence

We recently, characterized a novel peptide of the egg-laying controlling caudodorsal cells (CDC) of Lymnaea stagnalis. Here, we show that the novel peptide has autoinhibitory actions and its expression is significantly up-regulated in reproductively senescent animals. Intracellular recordings show that when bath-applied to the central nervous system in vitro, the peptide reduces the depolarizing after potential (DAP) in CDCs without affecting the action potential-threshold and -amplitude and the resting membrane potential. Moreover, peptide application can terminate an ongoing after discharge in the CDCs or, when electrical stimulation fails to induce an after discharge, can terminate the long-lasting depolarization. Semiquantitative peptide profiling by mass spectrometry demonstrated correct processing and targeting of peptides in the CDC somata and axon terminals of reproductively senescent animals. Interestingly, the level of the autoinhibitory peptide was selectively increased in the CDCs of reproductively senescent animals. Our results indicate that a shift in balance between excitatory and inhibitory auto-transmitter peptides in the CDC system of old non-egg-laying animals, plays a role in after discharge failure in CDCs of reproductively senescent Lymnaea.