title: Feedforward compensation mediated by the central and peripheral actions of a single neuropeptide discovered using representational difference analysis.
abstract: Compensatory mechanisms are often used to achieve stability by reducing variance, which can be accomplished via negative feedback during homeostatic regulation. In principle, compensation can also be implemented through feedforward mechanisms where a regulator acts to offset the anticipated output variation; however, few such neural mechanisms have been demonstrated. We provide evidence that an Aplysia neuropeptide, identified using an enhanced representational difference analysis procedure, implements feedforward compensation within the feeding network. We named the novel peptide "allatotropin-related peptide" (ATRP) because of its similarity to insect allatotropin. Mass spectrometry confirmed the peptide's identity, and in situ hybridization and immunostaining mapped its distribution in the Aplysia CNS. ATRP is present in the higher-order cerebral-buccal interneuron (CBI) CBI-4, but not in CBI-2. Previous work showed that CBI-4-elicited motor programs have a shorter protraction duration than those elicited by CBI-2. Here we show that ATRP shortens protraction duration of CBI-2-elicited ingestive programs, suggesting a contribution of ATRP to the parametric differences between CBI-4-evoked and CBI-2-evoked programs. Importantly, because Aplysia muscle contractions are a graded function of motoneuronal activity, one consequence of the shortening of protraction is that it can weaken protraction movements. However, this potential weakening is offset by feedforward compensatory actions exerted by ATRP. Centrally, ATRP increases the activity of protraction motoneurons. Moreover, ATRP is present in peripheral varicosities of protraction motoneurons and enhances peripheral motoneuron-elicited protraction muscle contractions. Therefore, feedforward compensatory mechanisms mediated by ATRP make it possible to generate a faster movement with an amplitude that is not greatly reduced, thereby producing stability.
authors.affiliation: Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA. jingj01@gmail.com
authors.forename: Jian
authors.initials: J
authors.lastname: Jing
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Sweedler
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Cropper
authors.forename: Vera
authors.initials: V
authors.lastname: Alexeeva
authors.forename: Ji-Ho
authors.initials: JH
authors.lastname: Park
authors.forename: Elena V
authors.initials: EV
authors.lastname: Romanova
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Nikolai C
authors.initials: NC
authors.lastname: Dembrow
authors.forename: Bjoern C
authors.initials: BC
authors.lastname: Ludwar
authors.forename: Klaudiusz R
authors.initials: KR
authors.lastname: Weiss
authors.forename: Ferdinand S
authors.initials: FS
authors.lastname: Vilim
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001048:Aplysia / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D003001:Cloning, Molecular / Q000379:methods; D004435:Eating / Q000187:drug effects; D025461:Feedback, Physiological / Q000187:drug effects*; D007301:Insect Hormones / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D007395:Interneurons / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D008954:Models, Biological; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D009068:Movement / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011863:Radioimmunoassay / Q000379:methods; D053719:Tandem Mass Spectrometry
chemical_list: D007301:Insect Hormones; D009479:Neuropeptides; C050669:allatotropin