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PLoS One. 2016 Jan 21;11(1):e0147335. doi: 10.1371/journal.pone.0147335. eCollection 2016.

Aplysia Locomotion: Network and Behavioral Actions of GdFFD, a D-Amino Acid-Containing Neuropeptide.

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State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Advanced Institute for Life Sciences, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
Beckman Institute for Advanced Science and Technology and Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.


One emerging principle is that neuromodulators, such as neuropeptides, regulate multiple behaviors, particularly motivated behaviors, e.g., feeding and locomotion. However, how neuromodulators act on multiple neural networks to exert their actions remains poorly understood. These actions depend on the chemical form of the peptide, e.g., an alternation of L- to D-form of an amino acid can endow the peptide with bioactivity, as is the case for the Aplysia peptide GdFFD (where dF indicates D-phenylalanine). GdFFD has been shown to act as an extrinsic neuromodulator in the feeding network, while the all L-amino acid form, GFFD, was not bioactive. Given that both GdFFD/GFFD are also present in pedal neurons that mediate locomotion, we sought to determine whether they impact locomotion. We first examined effects of both peptides on isolated ganglia, and monitored fictive programs using the parapedal commissural nerve (PPCN). Indeed, GdFFD was bioactive and GFFD was not. GdFFD increased the frequency with which neural activity was observed in the PPCN. In part, there was an increase in bursting spiking activity that resembled fictive locomotion. Additionally, there was significant activity between bursts. To determine how the peptide-induced activity in the isolated CNS is translated into behavior, we recorded animal movements, and developed a computer program to automatically track the animal and calculate the path of movement and velocity of locomotion. We found that GdFFD significantly reduced locomotion and induced a foot curl. These data suggest that the increase in PPCN activity observed in the isolated CNS during GdFFD application corresponds to a reduction, rather than an increase, in locomotion. In contrast, GFFD had no effect. Thus, our study suggests that GdFFD may act as an intrinsic neuromodulator in the Aplysia locomotor network. More generally, our study indicates that physiological and behavioral analyses should be combined to evaluate peptide actions.

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