Thomas Biederer, PhD
Research & Publications
Biography
News
Research Summary
Understanding synapse development – and how we get there
How synapses form to wire neurons into networks is a fundamental question of neuroscience. We pursue four long-term goals to understand this process. First, we define on molecular and cellular levels the signals that induce synapse formation. Second, we elucidate the intracellular pathways that control synaptogenesis. Third, we determine how the experience-dependent remodeling of neuronal connections is modulated by synapse-organizing proteins. Fourth, we analyze how synaptic aberrations contribute to brain disorders and how the maturation of neuronal connectivity can be supported. To pursue our goals, we combine biochemical, cell biological, physiological, and in vivo approaches. This integration enables mechanistic insights into synapse development and the profound disease relevance of synaptic biology.
Extensive Research Description
Bridging the cleft to induce synapse formation
How do synapses form? Select trans-synaptic interactions are now known to guide synapse development and we have identified and characterized synaptogenic cell adhesion molecules. One of these molecules, the immunoglobulin protein SynCAM 1, is required and sufficient to drive excitatory synapse formation in vivo. We build on this progress and analyze the functions of different synaptogenic adhesion proteins and how they cooperate.
In addition, we map the macromolecular and topological organization of the cleft of synapses using superresolution imaging and EM approaches. Our data support the concept that the synaptic cleft is comprised of structurally and molecularly diverse nanodomains. We are now testing the idea that the cleft is not static as widely assumed but a dynamic compartment, using methodologies including single particle tracking in live neurons. These studies can reveal how the sub-synaptic organization and dynamics of the cleft contribute to synaptic functions.
Synaptogenic signaling pathways
The intracellular signaling mechanisms instructing synapse development remain incompletely understood. Our work has shown that SynCAMs have signaling roles and we are elucidating these pathways. Analyzing synaptic changes in vivo, we have applied proteomic studies of synapses in mouse models with altered synaptogenesis to dissect signaling pathways. One example is our identification of the GTPase activator Farp1 as a novel postsynaptic protein that acts downstream of SynCAM adhesion and Semaphorin/Plexin signaling to promote synapse number and dendrite differentiation. We continue to elucidate how signaling pathways are integrated to control dendrite and synapse development.
Tuning networks
Synapse-organizing proteins not only allow neurons to connect but also impact neuronal networks once they are formed. This is underlined by a wealth of studies including from our group that synaptic adhesion proteins can modulate synaptic plasticity and impact memory processes. We address how synapse-organizing proteins contribute to the remodeling of neuronal connections. On the one hand, we investigate hippocampus-dependent memory processes. On the other, we use the paradigm of visual system plasticity to determine roles of trans-synaptic interactions in the experience-dependent maturation of cortical networks. This approach is based on in vivo electrophysiological recordings. Our work has translational potential as synaptic aberrations are a hallmark of autism-spectrum disorders and schizophrenia.
Coauthors
Research Interests
Biochemistry; Central Nervous System; Neurology; Neurosciences; Parkinson Disease; Schizophrenia; Synapses
Research Image
hippocampus
Selected Publications
- Concerted roles of LRRTM1 and SynCAM 1 in organizing prefrontal cortex synapses and cognitive functionsde Arce K, Ribic A, Chowdhury D, Watters K, Thompson G, Sanganahalli B, Lippard E, Rohlmann A, Strittmatter S, Missler M, Hyder F, Biederer T. Concerted roles of LRRTM1 and SynCAM 1 in organizing prefrontal cortex synapses and cognitive functions Nature Communications 2023, 14: 459. PMID: 36709330, PMCID: PMC9884278, DOI: 10.1038/s41467-023-36042-w.
- 69. CADM2 IS IMPLICATED IN IMPULSIVE PERSONALITY AND NUMEROUS OTHER TRAITS BY GENOME- AND PHENOME-WIDE ASSOCIATION STUDIES IN HUMANS, WITH FURTHER SUPPORT FROM STUDIES OF CADM2 MUTANT MICESanchez-Roige S, Jennings M, Thorpe H, Mallari J, van der Werf L, Bianchi S, Mallard T, Watters K, Biederer T, Team 2, Elson S, Fontanillas P, Khokhar J, Young J, Palmer A. 69. CADM2 IS IMPLICATED IN IMPULSIVE PERSONALITY AND NUMEROUS OTHER TRAITS BY GENOME- AND PHENOME-WIDE ASSOCIATION STUDIES IN HUMANS, WITH FURTHER SUPPORT FROM STUDIES OF CADM2 MUTANT MICE European Neuropsychopharmacology 2022, 63: e82-e83. DOI: 10.1016/j.euroneuro.2022.07.156.
- SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the SynapseKoopmans F, van Nierop P, Andres-Alonso M, Byrnes A, Cijsouw T, Coba M, Cornelisse L, Farrell R, Goldschmidt H, Howrigan D, Hussain N, Imig C, de Jong A, Jung H, Kohansalnodehi M, Kramarz B, Lipstein N, Lovering R, MacGillavry H, Mariano V, Mi H, Ninov M, Osumi-Sutherland D, Pielot R, Smalla K, Tang H, Tashman K, Toonen R, Verpelli C, Reig-Viader R, Watanabe K, van Weering J, Achsel T, Ashrafi G, Asi N, Brown T, De Camilli P, Feuermann M, Foulger R, Gaudet P, Joglekar A, Kanellopoulos A, Malenka R, Nicoll R, Pulido C, de Juan-Sanz J, Sheng M, Südhof T, Tilgner H, Bagni C, Bayés À, Biederer T, Brose N, Chua J, Dieterich D, Gundelfinger E, Hoogenraad C, Huganir R, Jahn R, Kaeser P, Kim E, Kreutz M, McPherson P, Neale B, O'Connor V, Posthuma D, Ryan T, Sala C, Feng G, Hyman S, Thomas P, Smit A, Verhage M. SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse Neuron 2019, 103: 217-234.e4. PMID: 31171447, PMCID: PMC6764089, DOI: 10.1016/j.neuron.2019.05.002.
- Synaptic Connectivity and Cortical Maturation Are Promoted by the ω-3 Fatty Acid Docosahexaenoic AcidCarbone BE, Abouleish M, Watters KE, Vogel S, Ribic A, Schroeder OH, Bader BM, Biederer T. Synaptic Connectivity and Cortical Maturation Are Promoted by the ω-3 Fatty Acid Docosahexaenoic Acid Cerebral Cortex 2019, 30: 226-240. PMID: 31034037, DOI: 10.1093/cercor/bhz083.
- Synapse-Selective Control of Cortical Maturation and Plasticity by Parvalbumin-Autonomous Action of SynCAM 1Ribic A, Crair MC, Biederer T. Synapse-Selective Control of Cortical Maturation and Plasticity by Parvalbumin-Autonomous Action of SynCAM 1 Cell Reports 2019, 26: 381-393.e6. PMID: 30625321, PMCID: PMC6345548, DOI: 10.1016/j.celrep.2018.12.069.
- Mapping the Proteome of the Synaptic Cleft through Proximity Labeling Reveals New Cleft ProteinsCijsouw T, Ramsey AM, Lam TT, Carbone BE, Blanpied TA, Biederer T. Mapping the Proteome of the Synaptic Cleft through Proximity Labeling Reveals New Cleft Proteins Proteomes 2018, 6: 48. PMID: 30487426, PMCID: PMC6313906, DOI: 10.3390/proteomes6040048.
- Transcellular Nanoalignment of Synaptic FunctionBiederer T, Kaeser PS, Blanpied TA. Transcellular Nanoalignment of Synaptic Function Neuron 2017, 96: 680-696. PMID: 29096080, PMCID: PMC5777221, DOI: 10.1016/j.neuron.2017.10.006.
- Excitatory Synaptic Drive and Feedforward Inhibition in the Hippocampal CA3 Circuit Are Regulated by SynCAM 1Park KA, Ribic A, Gaupp F, Coman D, Huang Y, Dulla CG, Hyder F, Biederer T. Excitatory Synaptic Drive and Feedforward Inhibition in the Hippocampal CA3 Circuit Are Regulated by SynCAM 1 Journal Of Neuroscience 2016, 36: 7464-7475. PMID: 27413156, PMCID: PMC4945666, DOI: 10.1523/jneurosci.0189-16.2016.
- Topographic Mapping of the Synaptic Cleft into Adhesive Nanodomainsde Arce K, Schrod N, Metzbower SWR, Allgeyer E, Kong G, Tang AH, Krupp AJ, Stein V, Liu X, Bewersdorf J, Blanpied TA, Lucić V, Biederer T. Topographic Mapping of the Synaptic Cleft into Adhesive Nanodomains Neuron 2015, 88: 1165-1172. PMID: 26687224, PMCID: PMC4687029, DOI: 10.1016/j.neuron.2015.11.011.
- Key Molecules: SynCAM Proteins☆Biederer T, Shrestha N. Key Molecules: SynCAM Proteins☆ 2015 DOI: 10.1016/b978-0-12-801238-3.04784-x.
- Activity-Dependent Regulation of Dendritic Complexity by Semaphorin 3A through Farp1Cheadle L, Biederer T. Activity-Dependent Regulation of Dendritic Complexity by Semaphorin 3A through Farp1 Journal Of Neuroscience 2014, 34: 7999-8009. PMID: 24899721, PMCID: PMC4044256, DOI: 10.1523/jneurosci.3950-13.2014.
- Structural organization and function of mouse photoreceptor ribbon synapses involve the immunoglobulin protein synaptic cell adhesion molecule 1Ribic A, Liu X, Crair MC, Biederer T. Structural organization and function of mouse photoreceptor ribbon synapses involve the immunoglobulin protein synaptic cell adhesion molecule 1 The Journal Of Comparative Neurology 2014, 522: 900-920. PMID: 23982969, PMCID: PMC3947154, DOI: 10.1002/cne.23452.
- The novel synaptogenic protein Farp1 links postsynaptic cytoskeletal dynamics and transsynaptic organizationCheadle L, Biederer T. The novel synaptogenic protein Farp1 links postsynaptic cytoskeletal dynamics and transsynaptic organization Journal Of Cell Biology 2012, 199: 985-1001. PMID: 23209303, PMCID: PMC3518221, DOI: 10.1083/jcb.201205041.
- The Synaptic Adhesion Molecule SynCAM 1 Contributes to Cocaine Effects on Synapse Structure and Psychostimulant BehaviorGiza JI, Jung Y, Jeffrey RA, Neugebauer NM, Picciotto MR, Biederer T. The Synaptic Adhesion Molecule SynCAM 1 Contributes to Cocaine Effects on Synapse Structure and Psychostimulant Behavior Neuropsychopharmacology 2012, 38: 628-638. PMID: 23169347, PMCID: PMC3572459, DOI: 10.1038/npp.2012.226.
- Specific N‐glycans on SynCAM Ig proteins regulate synaptic adhesion and synapse developmentBiederer T. Specific N‐glycans on SynCAM Ig proteins regulate synaptic adhesion and synapse development The FASEB Journal 2012, 26: 232.2-232.2. DOI: 10.1096/fasebj.26.1_supplement.232.2.
- Lateral assembly of the immunoglobulin protein SynCAM 1 controls its adhesive function and instructs synapse formationFogel AI, Stagi M, de Arce K, Biederer T. Lateral assembly of the immunoglobulin protein SynCAM 1 controls its adhesive function and instructs synapse formation The EMBO Journal 2011, 30: 4728-4738. PMID: 21926970, PMCID: PMC3243608, DOI: 10.1038/emboj.2011.336.
- SynCAM 1 Adhesion Dynamically Regulates Synapse Number and Impacts Plasticity and LearningRobbins EM, Krupp AJ, de Arce K, Ghosh AK, Fogel AI, Boucard A, Südhof TC, Stein V, Biederer T. SynCAM 1 Adhesion Dynamically Regulates Synapse Number and Impacts Plasticity and Learning Neuron 2010, 68: 894-906. PMID: 21145003, PMCID: PMC3026433, DOI: 10.1016/j.neuron.2010.11.003.
- N-Glycosylation at the SynCAM (Synaptic Cell Adhesion Molecule) Immunoglobulin Interface Modulates Synaptic Adhesion*Fogel AI, Li Y, Giza J, Wang Q, Lam TT, Modis Y, Biederer T. N-Glycosylation at the SynCAM (Synaptic Cell Adhesion Molecule) Immunoglobulin Interface Modulates Synaptic Adhesion* Journal Of Biological Chemistry 2010, 285: 34864-34874. PMID: 20739279, PMCID: PMC2966101, DOI: 10.1074/jbc.m110.120865.
- SynCAM 1 participates in axo-dendritic contact assembly and shapes neuronal growth conesStagi M, Fogel AI, Biederer T. SynCAM 1 participates in axo-dendritic contact assembly and shapes neuronal growth cones Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 7568-7573. PMID: 20368431, PMCID: PMC2867738, DOI: 10.1073/pnas.0911798107.
- SynCAMsFogel A, Biederer T. SynCAMs 2009, 823-828. DOI: 10.1016/b978-008045046-9.01352-8.
- [SY7.3]: SynCAM complexes encode synaptic adhesion to organize nascent synapsesFogel A, Stagi M, Krupp A, Stein V, Biederer T. [SY7.3]: SynCAM complexes encode synaptic adhesion to organize nascent synapses International Journal Of Developmental Neuroscience 2008, 26: 840-840. DOI: 10.1016/j.ijdevneu.2008.09.045.
- SynCAMs Organize Synapses through Heterophilic AdhesionFogel AI, Akins MR, Krupp AJ, Stagi M, Stein V, Biederer T. SynCAMs Organize Synapses through Heterophilic Adhesion Journal Of Neuroscience 2007, 27: 12516-12530. PMID: 18003830, PMCID: PMC6673342, DOI: 10.1523/jneurosci.2739-07.2007.
- Mixed-culture assays for analyzing neuronal synapse formationBiederer T, Scheiffele P. Mixed-culture assays for analyzing neuronal synapse formation Nature Protocols 2007, 2: 670-676. PMID: 17406629, DOI: 10.1038/nprot.2007.92.
- SynCAM in Formation and Function of Synaptic SpecializationsBiederer T. SynCAM in Formation and Function of Synaptic Specializations 2006, 125-135. DOI: 10.1007/978-0-387-32562-0_9.
- Identification of Endogenous/transfected Synaptic Proteins in Primary Neuronal Culture by a High-yield Immunogold LabelingLiu X, Han W, Biederer T, Kavalali E, Südhof T. Identification of Endogenous/transfected Synaptic Proteins in Primary Neuronal Culture by a High-yield Immunogold Labeling Microscopy And Microanalysis 2003, 9: 1498-1499. DOI: 10.1017/s1431927603447491.
- SynCAM, a Synaptic Adhesion Molecule That Drives Synapse AssemblyBiederer T, Sara Y, Mozhayeva M, Atasoy D, Liu X, Kavalali ET, Südhof T. SynCAM, a Synaptic Adhesion Molecule That Drives Synapse Assembly Science 2002, 297: 1525-1531. PMID: 12202822, DOI: 10.1126/science.1072356.
- CASK and Protein 4.1 Support F-actin Nucleation on Neurexins*Biederer T, Südhof T. CASK and Protein 4.1 Support F-actin Nucleation on Neurexins* Journal Of Biological Chemistry 2001, 276: 47869-47876. PMID: 11604393, DOI: 10.1074/jbc.m105287200.
- Mints as Adaptors DIRECT BINDING TO NEUREXINS AND RECRUITMENT OF Munc18*Biederer T, Südhof T. Mints as Adaptors DIRECT BINDING TO NEUREXINS AND RECRUITMENT OF Munc18* Journal Of Biological Chemistry 2000, 275: 39803-39806. PMID: 11036064, DOI: 10.1074/jbc.c000656200.