Synaptic Plasticity and Connectivity
Senior Team Leader
Synapse adhesion, Synaptic transmission, Plasticity
Synapse, a specialized zone of contact between two neurons, is the site at which communication takes place in the brain. Although neurons have reached the state of terminal differentiation, synapses continually form and are eliminated depending on the pattern of neural activity. The goal of our research is to delineate how experience in the form of synaptic activity shapes the structural organization of central synapses, and in turn, determines the connectivity pattern of neural networks. We hope to provide a molecular link for understanding processes that are thought to involve controlled changes in neural connectivity in the adult brain, such as memory consolidation. Our research program focuses on the structure-function relationship of synapses at three levels. The first goal is to understand how the state of synapse adhesion regulates the efficacy of synaptic transmission. We focus on the mechanisms by which integrins, cadherin-catenin complex, and signaling pathways that link to them modify neurotransmitter release and postsynaptic receptor activity to regulate synaptic plasticity. Second, we investigate how synapse adhesion proteins in turn, mediate activity-induced remodeling of pre and postsynaptic organization. Third, we address the nature of inter-synaptic organization with the premise that individual synapses are not autonomous but coordination between synapses plays an important role in shaping and maintaining functional neural networks. We study the axonal and dendritic mechanisms by which neighboring synapses communicate and regulate their synaptic strengths.
Synapses form at contact points between the dendrites of a cultured hippocampal neuron expressing YFP-actin (yellow) and axons from a CFP-actin expressing neurons (blue) whose cell bodies are present outside the field of view.
Park YK, and Goda Y: "Integrins in synapse regulation.", Nature Reviews Neuroscience, 17(12), 745-756 (2016)
Letellier M, Park YK, Chater TE, Chipman PH, Gautam SG, Oshima-Takago T, and Goda Y: "Astrocytes regulate heterogeneity of presynaptic strengths in hippocampal networks.", Proc Natl Acad Sci U S A (2016)
Shinoe T, and Goda Y: "Tuning synapses by proteolytic remodeling of the adhesive surface.", Curr Op Neurobiol, 35, 148-155 (2015)
Vitureira N, and Goda Y: "Cell biology in neuroscience: The interplay between Hebbian and homeostatic synaptic plasticity.", J Cell Biol, 203(2), 175-86 (2013)
McGeachie AB, Skrzypiec AE, Cingolani LA, Letellier M, Pawlak R, and Goda Y: "β3 integrin is dispensable for conditioned fear and Hebbian forms of synaptic plasticity in the hippocampus", Eur J Neurosci, 36(4), 2461-2469 (2012)
Pozo K, Cingolani LA, Bassani S, Laurent F, Passafaro M, and Goda Y: "β3 integrin interacts directly with GluA2 AMPA receptor subunit and regulates AMPA receptor expression in hippocampal neurons.", Proc Natl Acad Sci U S A (2012)
Vitureira N, Letellier M, White IJ, and Goda Y: "Differential control of presynaptic efficacy by postsynaptic N-cadherin and β-catenin.", Nat Neurosci (2011)
Pozo K, and Goda Y: "Unraveling mechanisms of homeostatic synaptic plasticity.", Neuron, 66(3), 337-51 (2010)
Staras K, Branco T, Burden JJ, Pozo K, Darcy K, Marra V, Ratnayaka A, and Goda Y: "A vesicle superpool spans multiple presynaptic terminals in hippocampal neurons.", Neuron, 66(1), 37-44 (2010)
Branco T, Staras K, Darcy KJ, and Goda Y: "Local dendritic activity sets release probability at hippocampal synapses.", Neuron, 59(3), 475-85 (2008)
Cingolani LA, Thalhammer A, Yu LM, Catalano M, Ramos T, Colicos MA, and Goda Y: "Activity-dependent regulation of synaptic AMPA receptor composition and abundance by beta3 integrins.", Neuron, 58(5), 749-62 (2008)