title: Presynaptic Muscarinic Acetylcholine Receptors and TrkB Receptor Cooperate in the Elimination of Redundant Motor Nerve Terminals during Development.
abstract: The development of the nervous system involves the overproduction of synapses but connectivity is refined by Hebbian activity-dependent axonal competition. The newborn skeletal muscle fibers are polyinnervated but, at the end of the competition process, some days later, become innervated by a single axon. We used quantitative confocal imaging of the autofluorescent axons from transgenic B6.Cg-Tg (Thy1-YFP)16 Jrs/J mice to investigate the possible cooperation of the muscarinic autoreceptors (mAChR, M1-, M2- and M4-subtypes) and the tyrosine kinase B (TrkB) receptor in the control of axonal elimination after the miceLevator auris longus (LAL)muscle had been exposed to several selective antagonist of the corresponding receptor pathwaysin vivo. Our previous results show that M1, M2and TrkB signaling individually increase axonal loss rate around P9. Here we show that although the M1and TrkB receptors cooperate and add their respective individual effects to increase axonal elimination rate even more, the effect of the M2receptor is largely independent of both M1and TrkB receptors. Thus both, cooperative and non-cooperative signaling mechanisms contribute to developmental synapse elimination.
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili Reus, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Nadal
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili Reus, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Garcia
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili Reus, Spain.
authors.forename: Erica
authors.initials: E
authors.lastname: Hurtado
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Simó
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili Reus, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Tomàs
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili Reus, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Lanuza
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili Reus, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Cilleros
authors.affiliation: Unitat d'Histologia i Neurobiologia (UHN), Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili Reus, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Tomàs
keywords: TrkB receptor; cholinergic synapses; motor nerve terminal; neuromuscular junction; presynaptic muscarinic acetylcholine receptors; synapse elimination