Trans-synaptic Signaling

The Trans-synaptic Signaling lab is interested in the mechanisms by which individual synapses, neurons and circuits dynamically adjust their transmission properties in response to changes in neuronal network activity.

To accomplish this, neurons signal to each other not only unidirectionally via classical pre to post-synaptic transmission, but also bidirectionally via pre or post-synaptic release of neuropeptides and neurotrophins. This bidirectional channel of communication is essential for the modulation of synapse and circuit strength, via regulation of distinct membrane fusion events on both sides of the synapse, including synaptic vesicle exocytosis, post-synaptic receptor recycling, and adhesion molecule recycling.

We investigate the mechanisms by which these trans-synaptic signaling events are regulated, at the level of single synapses, single neurons and neuronal networks, using a combination of live imaging approaches, electrophysiology, and biochemistry in neuronal cell culture and brain slices.

Our overall goal is to understand how neurons communicate changes in activity to affect circuit function, and ultimately behavior, during learning and memory acquisition, or to counteract aberrant brain states such as seizure activity. voltage imaging of activity in brain slices.

Topics: neurotrophins, synaptotagmins, synaptic transmission and plasticity, circuit function, organelle and vesicle transport, endocytosis, exocytosis.

Methods: live timelapse fluorescence imaging of reporter proteins in neuronal cell culture, voltage imaging of brain slices, photoactivation, pHluorins, channelrhodopsins, confocal and STED microscopy, electrophysiology, biochemistry

Selected recent publications:

  • Awasthi A, Ramachandran B, Ahmed S, Benito E, Shinoda Y, Nitzan N, Heukamp A, Rannio S, Martens H, Barth J, Burk K, Wang YT, Fischer A, Dean C. Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting. Science. 2019 Jan 4;363(6422)

  • Bharat V, Siebrecht M, Burk K, Ahmed S, Reissner C, Kohansal-Nodehi M, Steubler V, Zweckstetter M, Ting JT, Dean C. Capture of dense core vesicles at synapses by JNK-dependent phosphorylation of synaptotagmin-4. Cell Rep. 2017 Nov 21;21(8):2118-2133.

  • Benito E, Ramachandran B, Schroeder H, Schmidt G, Urbanke H, Burkhardt S, Capece V, Dean C, Fischer A. The BET/BRD inhibitor JQ1 improves brain plasticity in WT and APP mice, Transl Psychiatry. 2017 Sep 26;7(9).

  • Hurtado-Zavala JI, Ramachandran B, Ahmed S, Halder R, Bolleyer C, Awasthi A, Wagener RJ, Anderson K, Drenan RM, Lester HA, Miwa JM, Staiger JF, Fischer A, Dean C. TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus. Nat Commun. 2017 Jul 19;8:15878.

  • Burk K, Murdoch JD, Freytag S, Koenig M, Bharat V, Markworth R, Burkhardt S, Fischer A, Dean C. EndophilinAs regulate endosomal sorting of BDNF-TrkB to mediate survival signaling in hippocampal neurons. Sci Rep. 2017 May 19;7(1):2149.

  • Burk K, Ramachandran B, Ahmed S, Hurtado-Zavala JI, Awasthi A, Benito E, Faram R, Ahmad H, Swaminathan A, McIlhinney J, Fischer A, Perestenko P, Dean C. Regulation of Dendritic Spine Morphology in Hippocampal Neurons by Copine-6. Cereb Cortex. 2017 Feb 3:1-18.

The Syt Activity Project (Modulation of synaptic plasticity and circuit function by regulation of neurotrophin exocytosis) received funding from the Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 260916.

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