Cytokine + Growth Factor Reviews Vol[ 8\ No[ 0\ pp[ 0Ð6\ 0887 Þ 0887 Elsevier Science Ltd[ All rights reserved Printed in Great Britain 0248!5090:87 ,08[99¦9[99 PII] S0248Ð5090"86#99922Ð5 MINI REVIEW Neurotrophic Factors: Effects in Modulating Properties of the Neuro- muscular Endplate Michael Sendtner Besides their function in supporting neuronal survival\ neurotrophic factors in~uence various func! tional properties of responsive neurons[ In particular the role of these molecules in activity!mediated synaptic modulation has attracted great interest[ Motoneurons and their speci_c synapses with muscle cells\ the neuromuscular endplates\ are well!characterized structures which have been known for long to depend on trophic support\ at least during development[ This review summarizes recent _ndings about the role of neurotrophic factors in modulating synaptic ef_cacy of neuromuscular synapses\ both in an activity!dependent and !independent fashion[ Þ 0887 Elsevier Science Ltd[ All rights reserved[ Key words] synaptic plasticity = ciliary neurotrophic factor = neurotrophin!3 = neurotrophin!2 = brain!derived neurotrophic factor = motoneuron Among the most exciting _elds of modern neurobiology is the analysis of how the nervous system reacts and adapts to the manifold stimuli the organism is exposed to[ Except for a few regions in the brain\ most neurons are generated during early development\ and the capacity to develop new neurons by cell division and di}er! entiation from precursor cells is lost during early life[ Therefore\ the most e}ective mechanisms by which neu! rons can change their function is either by generation or elimination of synapses\ and:or by altering the functional properties of existing synapses[ In particular this _eld has received much attention during recent years[ The neuromuscular endplate is a well characterized and highly specialized synapse connecting motoneurons and muscle cells[ In fact\ the anatomical and functional changes occurring during development and in response to overstimulation or blockade were studied at this synapse long before techniques that allowed similar studies in other parts of the nervous system became available[ In the meantime\ a variety of molecules and mechanisms have been identi_ed which regulate neuromuscular trans! Klinische Forschergruppe Neuroregeneration\ Department of Neurology\ University of Wu  rzburg\ Josef!Schneider!Str 00\ D! 86979 Wu  rzburg\ Germany[ Tel[] 38!"9#820 190 4656^ Fax] 38! "9#820 190 1586^ E!mail] sendtnerÝmail[uni!wurzburg[de Address correspondence to] Dr M[ Sendtner\ University of Wu  rzburg\ Department of Neurology\ Josef!Schneider!Str 00\ D!86979 Wu  rzburg\ Germany[ 0 mission from both directions[ During development\ when motoneurons make their _rst contact with muscle cells\ they secrete ARIA\ a molecule which is necessary for the induction of acetylcholine receptor subunits expression ð0Ð2Ł[ Then\ electrical activity of the motoneurons represses AChR expression at extrasynaptic sites ð3Ł[ The secretion of agrin\ another signaling molecule\ from motoneurons into the synaptic cleft is necessary for the development and stabilization of the early synapses ð4Ł[ Both ARIA and agrin exert their speci_c functions on the development of neuromuscular synapses via speci_c tyrosine kinase receptors[ In the case of ARIA\ the e}ects are mediated through the erbB receptor tyrosine kinase ð2Ł\ in the case of agrin through a receptor complex involving the MuSK tyrosine kinase ð5\ 6Ł[ The clustering of AChR is not only induced by agrin\ but also by lam! inin!0\ a component of the extracellular matrix which mediates its e}ects on muscle cells in an agrin!inde! pendent fashion ð7Ł[ On the other side\ the muscle cells provide signals for developing motoneurons\ among them neurotrophic fac! tors[ It was recognized many years ago that motoneurons depend on target!derived molecules for their survival as soon as they have made contact with muscle cells[ Orig! inally\ it was assumed that this process helps to eliminate motoneurons which have not made correct contacts to their targets[ However\ this hypothesis has been con! tradicted by experimental evidence showing that neuro! muscular connections in developing chick embryos in