Glutamate Receptors in Synaptic Assembly and Plasticity: Case Studies on Fly NMJs

The molecular and cellular mechanisms that control the composition and functionality of ionotropic glutamate receptors may be considered as most important “set screws” for adjusting excitatory transmission in the course of developmental and experience-dep

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Glutamate Receptors in Synaptic Assembly and Plasticity: Case Studies on Fly NMJs Ulrich Thomas and Stephan J. Sigrist

Abstract The molecular and cellular mechanisms that control the composition and functionality of ionotropic glutamate receptors may be considered as most important “set screws” for adjusting excitatory transmission in the course of developmental and experience-dependent changes within neural networks. The Drosophila larval neuromuscular junction has emerged as one important invertebrate model system to study the formation, maintenance, and plasticity-related remodeling of glutamatergic synapses in vivo. By exploiting the unique genetic accessibility of this organism combined with diverse tools for manipulation and analysis including electrophysiology and state of the art imaging, considerable progress has been made to characterize the role of glutamate receptors during the orchestration of junctional development, synaptic activity, and synaptogenesis. Following an introduction to basic features of this model system, we will mainly focus on conceptually important findings such as the selective impact of glutamate receptor subtypes on the formation of new synapses, the coordination of presynaptic maturation and receptor subtype composition, the role of nonvesicularly released glutamate on the synaptic localization of receptors, or the homeostatic feedback of receptor functionality on presynaptic transmitter release. Keywords BMP signaling • Development • Glutamate receptors • Neuromuscular junction • Wnt signaling

U. Thomas (*) Leibniz Institute for Neurobiology, Brenneckestr. 6, 39118 Magdeburg, Germany e-mail: [email protected] S.J. Sigrist Genetics Institute of Biology, Freie Universit€at Berlin, Takustr. 6, 14195 Berlin, Germany e-mail: [email protected] M.R. Kreutz and C. Sala (eds.), Synaptic Plasticity, Advances in Experimental Medicine and Biology 970, DOI 10.1007/978-3-7091-0932-8_1, # Springer-Verlag/Wien 2012

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U. Thomas and S.J. Sigrist

Introduction

Excitatory synapses categorized as “glutamatergic” are no less heterogeneous than the many types of neurons that use glutamate in synaptic transmission. In-depth studies on a variety of glutamatergic synapses from different species are thus required to elucidate both general as well as subcategory-defining principles of synapse assembly, function, and plasticity. L-glutamate is the primary transmitter not only at the vast majority of excitatory synapses in the vertebrate CNS but also at arthropod neuromuscular junctions (NMJs). Concerning the latter, illuminative physiological, pharmacological, and ultrastructural analyses have been performed on NMJs from various crustacean and insect model organisms. Undeniably, Drosophila has reached a pole position in this respect, mainly because of its unbeatable genetic accessibility. Preceded by pilot studies from Jan and Jan (1976a, b), thorough electrophysiological and morphological studies on NMJs from both wild-type and excitability mutants paved the road for intensive