Laboratory for Synaptic Plasticity and Connectivity

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.

Research Subjects

• regulation of synaptic strength by integrins
• trans-synaptic moducation of pre and postsynaptic strengths by N-cadherin
• interaction between Hebbian and homeostatic synaptic plasticities

Publications

1. McGeachie AB, Skrzypiec AE, Cingolani LA, Letellier M, Pawlak R, and Goda Y.:
   "Beta3 integrin is dispensable for conditioned fear and Hebbian forms of synaptic plasticity in the hippocampus"
   Eur J Neurosci, 36(4), 2461-2469 (2012)
2. Pozo K, Cingolani LA, Bassani S, Laurent F, Passafaro M, and Goda Y.:
   "Beta3 integrin interacts directly with GluA2 AMPA receptor subunit and regulates AMPA receptor expression in hippocampal neurons"
   Proc Natl Acad Sci USA 109:1323-1328 (2012)
3. Vitureira N, Letellier M, White IJ, and Goda Y.:
   "Differential control of presynaptic efficacy by postsynaptic N-cadherin and beta-catenin"
   Nat Neurosci 15:81-89 (2011)
4. Vitureira N, Letellier M, and Goda Y.:
   "Homeostatic synaptic plasticity: from single synapses to neural circuits"
   Curr Opin Neurobiol, 22(3), 516-521 (2011)
5. Pozo K, and Goda Y.:
   "Unraveling mechanisms of homeostatic synaptic plasticity"
   Neuron, 66(3), 337-51 (2010)
6. Stras K, Branco T, Burden JJ, Pozo K, Darcy K, Marra V, Ratnayaka A, Goda Y,:
   "A Vesicle superpool spanning multiple presynaptic terminals in hippocampal neurons"
   Neuron 66, 36-44 (2010)
7. Tokuoka H, Goda Y.:
   "Activity-dependent coordination of presynaptic release probability and postsynaptic GluR2 abundance at single synapses"
   Proc Natl Acad Sci USA 105, 14656-14661 (2008)
8. Branco T, Staras K, Darcy KJ, Goda Y.:
   "Local dendritic activity sets release probability at hippocampal synapses"
   Neuron 58, 749-762 (2008)
9. Cingolani LA, Thalhammer A, Yu LM, Catalano M, Ramos T, Colicos MA, Goda Y.:
   "Activity-dependent regulation of synaptic AMPA receptor composition and abundance by β3 integrins"
   Neuron 58, 749-762 (2008)
10. Cingolani LA, Goda Y.:
    "Action in Action: The interplay of action cytoskeleton and synaptic efficacy"
    Nat Rev Neurosci 9, 344-356 (2008)