Advances in the labelling and selective manipulation of synapses

Aimino, M. A., Humenik, J., Parisi, M. J., Duhart, J. C. & Mosca, T. J. SynLight: a bicistronic strategy for simultaneous active zone and cell labeling in the Drosophila nervous system. G3 13, jkad221 (2023).

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Talay, M. et al. Transsynaptic mapping of second-order taste neurons in flies by trans-Tango. Neuron 96, 783–795 (2017).

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Oh, J.-Y. et al. Labeling dual presynaptic inputs using cfork anterograde tracing system. Exp. Neurobiol. 29, 219–229 (2020).

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Cachero, S. et al. BAcTrace, a tool for retrograde tracing of neuronal circuits in Drosophila. Nat. Methods 17, 1254–1261 (2020). This work uses an engineered form of the Clostridium botulinum neurotoxin A (Botox) that is capable of retrograde trans-synaptic labelling via the activation of a silent transcription factor in the neuron.

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Huang, T.-H. et al. Tracing neuronal circuits in transgenic animals by transneuronal control of transcription (TRACT). eLife 6, e32027 (2017).

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Choi, J. H. et al. Interregional synaptic maps among engram cells underlie memory formation. Science 360, 430–435 (2018). This paper introduced an advance in the GRASP technique that allowed multicolour labelling of engram and non-engram synapses.

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Kim, J. et al. mGRASP enables mapping mammalian synaptic connectivity with light microscopy. Nat. Methods 9, 96–102 (2012). In this work, the GRASP technique was upgraded so that it was applicable to mammalian neurons, in which it labels synapses using split green fluorescent protein expressed as part of presynaptic and postsynaptic partner proteins.

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Son, S. et al. Real-time visualization of structural dynamics of synapses in live cells in vivo. Nat. Methods 21, 353–360 (2024). This paper introduced a method for real-time visualization of the structural plasticity of synapses in vivo using dimerization-dependent fluorescent proteins.

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Feinberg, E. H. et al. GFP reconstitution across synaptic partners (GRASP) defines cell contacts and synapses in living nervous systems. Neuron 57, 353–363 (2008). This paper initiated the concept of using split green fluorescent protein to label presynaptic and postsynaptic interactions.

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Kim, T. et al. Activated somatostatin interneurons orchestrate memory microcircuits. Neuron 112, 201–208 (2023).

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Trimmer, J. S. Genetically encoded intrabodies as high-precision tools to visualize and manipulate neuronal function. Semin. Cell Dev. Biol. 126, 117–124 (2022).

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Ferro, M. et al. Functional mapping of brain synapses by the enriching activity-marker SynaptoZip. Nat. Commun. 8, 1229 (2017).

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Chen, Y. et al. Cell-type-specific labeling of synapses in vivo through synaptic tagging with recombination. Neuron 81, 280–293 (2014).

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Perez-Alvarez, A. et al. Freeze-frame imaging of synaptic activity using SynTagMA. Nat. Commun. 11, 2464 (2020).

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Lee, C. et al. Hippocampal engram networks for fear memory recruit new synapses and modify pre-existing synapses in vivo. Curr. Biol. 33, 507–516 (2023).

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Ma, S. & Zuo, Y. Synaptic modifications in learning and memory — a dendritic spine story. Semin. Cell Dev. Biol. 125, 84–90 (2022).

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Sørensen, A. T. et al. A robust activity marking system for exploring active neuronal ensembles. eLife 5, e13918 (2016).

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Ortega-de San Luis, C. & Ryan, T. J. Understanding the physical basis of memory: molecular mechanisms of the engram. J. Biol. Chem. 298, 101866 (2022).

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Rao-Ruiz, P. et al. Engram-specific transcriptome profiling of contextual memory consolidation. Nat. Commun. 10, 2232 (2019).

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Josselyn, S. A., Köhler, S. & Frankland, P. W. Finding the engram. Nat. Rev. Neurosci. 16, 521–534 (2015).

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Choi, D. I. & Kaang, B. K. Interrogating structural plasticity among synaptic engrams. Curr. Opin. Neurobiol. 75, 102552 (2022). This review delves into the concept of engram synapses and the approaches used to label them.

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Ryan, T. J., Roy, D. S., Pignatelli, M., Arons, A. & Tonegawa, S. Engram cells retain memory under retrograde amnesia. Science 348, 1007–1013 (2015).

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Farhy-Tselnicker, I. & Allen, N. J. Astrocytes, neurons, synapses: a tripartite view on cortical circuit development. Neural Dev. 13, 1–12 (2018).

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Silbereis, J. C., Pochareddy, S., Zhu, Y., Li, M. & Sestan, N. The cellular and molecular landscapes of the developing human central nervous system. Neuron 89, 248–268 (2016).

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Lin, Y. C. & Koleske, A. J. Mechanisms of synapse and dendrite maintenance and their disruption in psychiatric and neurodegenerative disorders. Annu. Rev. Neurosci. 33, 349–378 (2010).

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Peça, J. & Feng, G. Cellular and synaptic network defects in autism. Curr. Opin. Neurobiol. 22, 866–872 (2012).

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Rubinov, M. & Bullmore, E. Fledgling pathoconnectomics of psychiatric disorders. Trends Cogn. Sci. 17, 641–647 (2013).

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Mevel, K. & Fransson, P. The functional brain connectome of the child and autism spectrum disorders. Acta Paediatr. 105, 1024–1035 (2016).

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Narr, K. L. & Leaver, A. M. Connectome and schizophrenia. Curr. Opin. Psychiatry 28, 229–235 (2015).

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Sacai, H. et al. Auti

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