title: Cell adhesion and homeostatic synaptic plasticity.
abstract: At synapses, pre- and post-synaptic cells get in direct contact with each other via cell adhesion molecules (CAMs). Several CAMs have been identified at the neuromuscular junction and at central synapses, where they regulate synaptic strength, by recruiting scaffolding proteins, neurotransmitter receptors and synaptic vesicles in response to the binding of counter-receptors across the synaptic cleft. Many synapses are also surrounded by astrocytic processes and embedded in conspicuous extracellular matrix (ECM). It is now widely recognized that astrocytes play a central role in regulating the synaptic machinery by exchanging information with the neuronal elements via diffusible molecules and direct physical interactions; this has lead to the concept of the 'tri-partite synapse'. More recently, the term 'tetra-partite synapse' has been introduced to underlie the importance of ECM in shaping synaptic function by mediating interaction and signaling between neurons and astrocytes. Here, we will review how this integrated view of the synapse can help us understand homeostatic synaptic plasticity at the neuromuscular junction and in the central nervous system. We will explore how synaptic CAMs regulate two forms of homeostatic plasticity: (i) postsynaptic scaling of synaptic currents to counteract changes in neuronal network activity and (ii) the compensatory modulation of presynaptic neurotransmitter release in response to changes in postsynaptic efficacy. We will discuss recent findings on activity-dependent trans-synaptic signaling events and the role of cell adhesion in the feedback control of network activity. This article is part of the Special Issue entitled 'Homeostatic Synaptic Plasticity'.
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia (IIT), Via Morego 30, 16163 Genoa, Italy.
authors.forename: Agnes
authors.initials: A
authors.lastname: Thalhammer
authors.affiliation: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia (IIT), Via Morego 30, 16163 Genoa, Italy. Electronic address: lorenzo.cingolani@iit.it.
authors.forename: Lorenzo A
authors.initials: LA
authors.lastname: Cingolani
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D009473:Neuronal Plasticity; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules
keywords: 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid receptor; ADAM; AMPAR; BDNF; CAM; CDK5; CaMKIV; Cadherin; Catenin; Cdk5; Cell adhesion; ECM; Eph receptor; GABA; GAP; GEF; GTPase-activating protein; GluA2; Homeostatic synaptic plasticity; Integrin; LTD; LTP; MHC; Major histocompatibility complex; N-Methyl-d-aspartate receptor; NMDAR; Neurexin; PDZ; Rap; Release probability; Synaptic scaling; TNFα; a disintegrin and metalloprotease; brain-derived neurotrophic factor; calcium/calmodulin-dependent protein kinase IV; cell adhesion molecules; cyclin-dependent kinase 5; extracellular matrix; gamma-aminobutyric acid; guanine nucleotide exchange factor; long-term depression; long-term potentiation; postsynaptic density protein/Drosophila disc large tumor suppressor/zonula occludens-1 protein; tumor necrosis factor alpha