Recent Scientific Findings

Zhang, X., Chen, X., Matúš, D., and Südhof, T.C. (2025) Reconstitution of synaptic junctions orchestrated by teneurin-latrophilin complexes. Science 387, 322-329.    

Synapses are organized by trans-synaptic adhesion molecules that coordinate assembly of pre- and postsynaptic specializations that are composed of scaffolding proteins forming liquid-liquid phase-separated condensates. Presynaptic teneurins mediate excitatory synapse organization by binding to postsynaptic latrophilins; however, the mechanism of action of teneurins, driven by extracellular domains evolutionarily derived from bacterial toxins, was unclear, as was the potential coupling of teneurins to presynaptic scaffolding proteins. In this paper we show that only the intracellular sequence of Teneurin-3, a dimerization sequence, and the extracellular bacterial toxin–derived latrophilin binding domains of Teneurin-3 are required for synapse organization, suggesting that teneurin-induced latrophilin clustering mediates synaptogenesis. We demonstrate that intracellular Teneurin-3 sequences capture liquid-liquid phase-separated presynaptic active zone scaffolds, which enabled us to reconstitute an entire synaptic junction from purified proteins in which trans-synaptic teneurin-latrophilin complexes recruit phase separated pre- and postsynaptic specializations.

Model of the mechanism of teneurin/latrophilin-mediated synapse formation. The cartoon summarizes the trans-synaptic interactions mediated by latrophilins and their teneurin and FLRT ligands and the cytoplasmic recruitment of pre- and postsynaptic phase-separated scaffold proteins by teneurins and latrophilins, respectively. The model posits that the trans-synaptic teneurin-latrophilin complex organizes and aligns pre- and postsynaptic specializations via protein interaction networks that require, among others, dimerization of latrophilins by teneurins and latrophilin GPCR signaling (adapted from Zhang et al., 20250.)

Liu, Z., Sun, W., Jiang, X., Ng, Yl.H., Dong, H., Liu, J., Quake, S.R., and Südhof, T.C. (2024) The Cortical Amygdala Consolidates a Socially Transmitted Long-term Memory. Nature 632, 366-374. 

Mice and other animals are able to communicate to each other whether a food is ‘good’ during a process called “social transmission of food preference” (STFP). In this paradigm, a hungry mouse smells in the breath of another mouse a food odor, leading it to prefer food with this odor in future. STFP memory formation  is an ecologically relevant memory paradigm that requires the social context and that represents a one-trial learning paradigm that produces a memory lasting for weeks and even months.  In this paper, we show that the posteromedial nucleus of the cortical amygdala (COApm) serves as a computational center in long-term STFP memory consolidation by integrating social and sensory olfactory inputs. Blocking synaptic signaling by the COApm-based circuit selectively abolished STFP memory consolidation without impairing memory acquisition, storage or recall. COApm mediated STFP memory consolidation depends on synaptic inputs from the accessory olfactory bulb and on synaptic outputs to the anterior olfactory nucleus. STFP memory consolidation requires protein synthesis, suggesting a gene-expression mechanism. Deep single-cell and spatially resolved transcriptomics revealed robust but distinct gene-expression signatures induced by STFP memory formation in the COApm that are consistent with synapse restructuring. These data thus defined a neural circuit for the consolidation of a socially communicated long-term memory, thereby mechanistically distinguishing protein-synthesis-dependent memory consolidation from memory acquisition, storage or retrieval.

Social transmission of food preference (STFP) in mice produces a long-term memory that can reverse a mouse’s innate food preference, requires the posteromedial nucleus of the cortical amygdala (COApm) for consolidation, and involves profound gene expression changes. A & B, Mice exhibit a strong innate food preference for cocoa over cinnamon (A) that can be reversed by social transmission of food preference (B). C, Mapping of the circuits involved in long-term STFP memory formation uncovered an essential for the cortical amygdala COApm in addition to the known involvement of the piriform cortex, ventral hippocampus, and accessory olfactory nucleus (AON). Moreover, these experiments revealed that social signals transmitted by accessory olfactory bulb (AOB) inputs to the COApm are as essential as olfactory sensory inputs into the piriform cortex transmitted by the main olfactory bulb (MOB). D, Representative Merfish image for mapping spatial transcriptomics use to uncover STFP-specific gene expression changes. E, STFP long-term memory consolidation in the COApm involves major gene expression changes that prominently include synaptic adhesion GPCRs.  

Wang, S., DeLeon, C., Sun, W., Quake, S.R., Roth, B.L., and Südhof, T.C. (2024) Alternative Splicing of Latrophilin-3 Controls Synapse Formation. Nature 626, 128-135.

Our previous work had shown that latrophilin-3 (Lphn3) is essential for Schaffer-collateral CA3  CA1 synapses and that its function requires the binding sites for teneurins and FLRTs and the Lphn3 GPCR signaling activity. Thus, we asked in this study how Lphn3 organizes Schaffer-collateral synapses. We first described an extensive cell type-specific alternative splicing of Lphn3 that is regulated by activity, We then showed that the Gα specificity of Lphn3 is tightly regulated by this alternative splicing, resulting in LPHN3 variants that predominantly signal through Gαs or Gα12/13. We next used CRISPR-mediated manipulation of Lphn3 alternative splicing that shifts LPHN3 from a Gαs- to a Gα12/13-coupled mode in vivo, demonstrating that the loss of the Gαs-coupled Lphn3 splice variant impaired synaptic connectivity as severely as the overall deletion of Lphn3. Notably, we found that the Gαs-coupled, but not the Gα12/13-coupled, splice variants of Lphn3 also recruited phase-transitioned postsynaptic protein scaffold condensates, such that these condensates are clustered by binding of presynaptic teneurin and FLRT ligands to Lphn3. Together, these data indicate that activity-dependent alternative splicing of a key synaptic adhesion molecule controls synapse formation by parallel activation of two convergent pathways: Gαs signaling and clustered phase separation of postsynaptic protein scaffolds.

Extensive alternative splicing of the C-terminal sequences of latrophilin-3 (Lphn3) regulates Ga signaling, synapse formation, and recruitment of phase-separated postsynaptic protein scaffolds. A, Schematic of the alternative splicing of Lphn3. B, summary of the Ga protein coupling strengths, cAMP signaling, and Shank binding of Lphn3 splice variants. Note that the alternatively spliced upstream Exon24 serves as a gate that is then further diversified by downstream alternative splicing of Exons 28-32. C, The selective ablation of Exon31 that is essential for Ga and cAMP signaling and Shank binding by CRISP-mediated in vivo manipulations impair synaptic connectivity in Schaffer collateral synapses as much as the outright deletion of Lphn3 as measured by trans-synaptic rabies virus tracing. D, Lphn3 recruits phase-separated postsynaptic scaffolding proteins in a manner requiring Exon31. All data were adapted from Wang et al. (2025).  

Zhou, B., Lu, J.G., Siddu, A., Wernig, M., and Südhof, T.C. (2022) Synaptogenic Effect of APP-Swedish Mutation in Familial Alzheimer’s Disease. Science Transl. Medicine, 14, eabn9380. PMCID: PMC9894682    

Mutations in β-amyloid (Aβ) precursor protein (APP) cause familial Alzheimer's disease (AD) probably by enhancing Aβ peptides production from APP. An antibody targeting Aβ (aducanumab) was approved as an AD treatment; however, some Aβ antibodies have been reported to accelerate, instead of ameliorating, cognitive decline in individuals with AD. Using conditional APP mutations in human neurons for perfect isogenic controls and translational relevance, we found that the APP-Swedish mutation in familial AD increased synapse numbers and synaptic transmission, whereas the APP deletion decreased synapse numbers and synaptic transmission. Inhibition of BACE1, the protease that initiates Aβ production from APP, lowered synapse numbers, suppressed synaptic transmission in wild-type neurons, and occluded the phenotype of APP-Swedish-mutant neurons. Modest elevations of Aβ, conversely, elevated synapse numbers and synaptic transmission. Thus, the familial AD-linked APP-Swedish mutation under physiologically relevant conditions increased synaptic connectivity in human neurons via a modestly enhanced production of Aβ. These data are consistent with the relative inefficacy of BACE1 and anti-Aβ treatments in AD and the chronic nature of AD pathogenesis, suggesting that AD pathogenesis is not simply caused by overproduction of toxic Aβ but rather by a long-term effect of elevated Aβ concentrations.

Synaptogenic Effect of APP-Swedish Mutation in Familial Alzheimer’s Disease

List of Recent Publications

1.     Zhang, X., Chen, X., Matúš, D., and Südhof, T.C. (2025) Reconstitution of synaptic junctions orchestrated by teneurin-latrophilin complexes. Science 387, 322-329. PMID: 39818903

2.     Liu, Z., Sun, W., Jiang, X., Ng, Yl.H., Dong, H., Liu, J., Quake, S.R., and Südhof, T.C. (2024) The Cortical Amygdala Consolidates a Socially Transmitted Long-term Memory. Nature 632, 366-374. PMID: 38961294

3.     Liakath-Ali, K., Raffee, R., and Südhof, T.C.  Cartography of Teneurin and Latrophilin Expression Reveals Spatiotemporal Axis Heterogeneity in the Mouse Hippocampus during Development (2024) PLOS Biology 22, e3002599. PMID: 38713721

4.     Wang, S., DeLeon, C., Sun, W., Quake, S.R., Roth, B.L., and Südhof, T.C. (2024) Alternative Splicing of Latrophilin-3 Controls Synapse Formation. Nature 626, 128-135. PMID: 38233523

5.     Matúš, D., Lopez, J.M., Sando, R.C., and Südhof, T.C.  The Essential Role of Latrophilin-1 Adhesion GPCR Nanoclusters in Inhibitory Synapses (2024) J. Neurosci. 44, e1978232024. PMID: 38684366

6.     Sun, W., Liu, Z., Jiang, X., Chen, M.B., Dong, H., Liu, J., Südhof, T.C., and Quake, S. R. (2024) Spatial and single-cell transcriptomics reveal neuron-astrocyte interplay in long-term memory. Nature 627, 374-381. PMID: 38326616

7.    Liu, Y., Wang, J., Südhof, T.C., and Wernig M. Efficient generation of functional neurons from mouse embryonic stem cells via neurogenin-2 expression. (2023) Nat. Protoc. 10, 2954-2974. PMID: 37596357.

8.    Sclip A., and Südhof, T.C. Combinatorial Expression of Neurexins and LAR-type Phosphotyrosine Phosphatase Receptors Instructs Assembly of a Cerebellar Circuit. (2023) Nat. Commun. 14, 4976. PMID: 37591863

9.    Essayan-Perez, S., and Südhof, T.C. Neuronal gamma-secretase regulates lipid metabolism, linking cholesterol to synaptic dysfunction in Alzheimer’s disease. (2023) Neuron 111, 3176-3194. PMID: 37543038

10.    Albarran, E., Liu, Y., Raju, K., Dong, A., Cui, L., Shen, J., Li, Y., Südhof, T.C., and Ding, J. Postsynaptic synucleins mediate endocannabinoid signaling. (2023) Nature Neurosci. 26, 997-1007. PMID: 37248337

11.  Trotter, J.H., Wang, C.Y., Zhou, P., Nakahara, G., and Südhof, T.C. A combinatorial code of neurexin-3 alternative splicing controls inhibitory synapses via a trans-synaptic dystroglycan signaling loop. (2023) Nat. Commun. 14, 1771. PMID: 36997523

12.  Hale, W.D., Südhof, T.C., and Huganir, R.L. Engineered Adhesion Molecules Drive Synapse Organization. (2023) Proc. Natl. Acad. Sci. U.S.A. 120, e2215905120. PMID: 36638214

13.  Lin, P.Y., Chen, L.Y., Jiang, M., Trotter, J.H., Seigneur, E., and Südhof, T.C. Neurexin-2: An Inhibitory Neurexin That Restricts Excitatory Synapse Formation in the Hippocampus. (2023) Sci. Advances 9, eadd8856. PMID: 36608123

14.  Wang, L., Mirabella, V., Dai, R., Su, X., Xu, R., Jadali, A., Bernabucci, M., Singh, I., Chen, Y. Tian, J., Jiang, P., Kwan, K., Pak, C.H., Liu, C., Comoletti, D., Hart, R., Chen, C., Südhof, T.C., and Pang, Z. Analyses of the autism-associated neuroligin-3 R451C mutation in human neurons reveal a gain-of-function synaptic mechanism. (2022) . Mol. Psychiatry in press. PMID: 36280753

15.  Zhou, B., Lu, J.G., Siddu, A., Wernig, M., and Südhof, T.C. Synaptogenic Effect of APP-Swedish Mutation in Familial Alzheimer’s Disease. (2022) Science Transl. Medicine, 14, eabn9380.  PMID: 36260691

16.  Bahareh Haddad Derafshi, B.H., Danko, T., Chanda, S., Batista, P.J., Litzenburger, U., Lee, Q.Y., Ng, Y.H., Sebin, A., Kumar, I., Chang, H.Y., Südhof, T.C., Wernig, M. The Autism Risk Factor CHD8 Is a Chromatin Activator in Human Neurons and Functionally Dependent on the ERK-MAPK Pathway Effector ELK1. (2022) . Sci. Reports 12, 22425. PMID: 36575212

17.  Dai, J., Liakath-Ali, K., Golf, S., and Südhof, T.C. Distinct Neurexin-Cerebellin Complexes Control AMPA- and NMDA-Receptor Responses in a Circuit-Dependent Manner. (2022) . E-Life 11, e78649. PMID: 36205393

18.  Eichel, K., Uenaka, T., Belapurkar, V., Lu, R., Cheng, S., Pak, J.S., Taylor, C.A., Südhof T.C., Malenka, R., Wernig, M., Özkan, E., Perrais, D., and Shen, K. Endocytosis in the axon initial segment maintains neuronal polarity. (2022) Nature 609, 128-135. PMID: 35978188

19.  Han, Y., Cao, R., Qin, L., Chen, L.Y., Tang, A.H., Südhof, T.C., and Zhang, B. Neuroligin-3 confines AMPA-receptors into nanoclusters, thereby controlling synaptic strength at the calyx of Held synapses. (2022) Science Advances, 17, eabo4173. PMID: 35704570

20.  Burlingham, S, Wong, N., Petterkin, L., Lubow, L., Dos Santos Passos, C., Benner, O., Ghebrial, M., Cast, T., Xu-Friedman, M., Südhof, T.C., and Chanda, S. Induction of Synapse Formation by De Novo Neurotransmitter Synthesis. (2022) Nature Comm. 13, 3060. PMID: 35650274

21.  Wöhr, M., Fong WM, Janas JA, Mall M, Thome C, Vangipuram M, Meng L, Südhof, T.C., and Wernig, M. Myt1l haploinsufficiency leads to obesity and multifaceted behavioral alterations in mice. (2022) Mol. Autism, 13, 19.  PMID: 35538503

22.  Zhang, X., Lin, P.Y., Liakath-Ali, K, and Südhof, T.C. Teneurins Assemble into Presynaptic Nanoclusters that Promote Synapse Formation via Postsynaptic Non-Teneurin Ligands. (2022) Nature Comm. 13, 2297. PMID: 35484136

23.  Liakath-Ali, K., Polepalli, J.S., Lee, S.J., Cloutier, J.F., and Südhof, T.C. Transsynaptic Cerebellin 4-Neogenin 1 Signaling Mediates LTP in the Mouse Dentate Gyrus. (2022) Proc. Natl. Acad. Sci. U.S.A. 119, e2123421119 PMID: 35544694

24.  Liu, Z., Jiang, M., Liakath-Ali, K., Sclip, A., Ko, J., Zhang, R.S., and Südhof, T.C. Deletion of Calsyntenin-3, an atypical cadherin, suppresses inhibitory synapses but increases excitatory parallel-fiber synapses in cerebellum. (2022) E-Life 11, e70664 PMID: 35420982

25.  Shibuya, Y., Kumar, K.K., Mader, M.M., Yoo, Y., Ayala, L.A., Zhou, M., Mohr, M.A., Neumayer, G., Kumar, I., Yamamoto, R., Marcoux P., Liou, B., Bennett, F.C., Nakauchi, H., Sun, Y., Chen, X., Heppner, F.L., Wyss-Coray, T., Südhof, T.C., and Wernig, M. Treatment of a genetic brain disease by CNS-wide microglia replacement. (2022) Sci Transl Med. 14, eabl9945. PMID: 35294256

26.  Shankhwar, S., Schwarz, K., Katiyar, R., Jung, M., Maxeiner, S., Südhof, T.C., Schmitz, F. RIBEYE B-domain is essential for RIBEYE A-domain stability and assembly of synaptic ribbons. (2022) Front. Mol. Neurosci. 15, 838311 PMID: 35153673

27.  Trotter, J.H., Dargaei, Z., Sclip, A., Essayan-Perez, S., Liakath-Ali, K., Raju, K., Nabet, A., Liu, X., and Südhof, T.C. Compartment-Specific Neurexin Nanodomains Orchestrate Tripartite Synapse Assembly (2021) Preprint. DOI: 10.1101/2020.08.21.262097

28.  Wang, C.Y., Trotter, J.H., Liakath-Ali, K., Lee, S.J., Liu, X., and Südhof, T.C. Molecular Self-Avoidance in Synaptic Neurexin Complexes. (2021) Science Advances 7, eabk1924. PMID: 34919427

29.  Sando, R., Ho, M.L., Liu, X., and Südhof, T.C. Engineered Synaptic Tools Reveal Localized cAMP Signaling in Synapse Assembly. (2022) J. Cell Biol. 221, e202109111. PMID: 34913963

30.  Wang, J., Miao, Y., Wicklein, R., Sun, Z., Wang, J., Jude, K.M., Fernandes, R.A., Merrill, S.A., Wernig, M., Garcia, K.C., and Südhof, T.C. RTN4/NoGo-Receptor Binding to BAI Adhesion-GPCRs Regulates Neuronal Development. (2021) Cell 184, 5869-5885. PMID: 34758294

31.  Ng, Y.H., Chanda, S.,Janas, J.A., Yang, N., Kokubu, Y., Südhof, T.C., and Wernig, M. Efficient generation of dopaminergic induced neuronal cells with midbrain characteristics. (2021) Stem Cell Rep. 16, 1763-1776. PMID: 34171286

32.  Seigneur, E., Polepalli, J., Wang, J., Dai, J., and Südhof, T.C. Cerebellin-2 Regulates a Serotonergic Dorsal Raphe Circuit that Controls Compulsive Behaviors. (2021) PMID: 34158618

33.  Dai, J., Patzke, C., Liakath-Ali, K., Seigneur, E., and Südhof, T.C. GluD1 is a signal transduction device disguised as an ionotropic receptor. (2021) . Mol. Psychiatry. 26, 7509-7521. PMID: 34135511

34.  Pak, C., Danko, T., Mirabella, V.R., Wang, J., Liu, Y., Vangipuram, M., Grieder, S., Zhang, X., Ward, T., Huang, Y.W.A., Jin, K., Dexheimer, P., Bardes, E., Mittelpunkt, A., Ma, J., McMachlan, M., Moore, J.C., Qu, P., Purmann, C., Dage, J.L., Swanson, B.J., Urban A.E., Aronow, B.J., Pang, Z.P., Levinson, D.F., Wernig, M., and Südhof, T.C. Cross-Platform Validation of Neurotransmitter Release Impairments in Schizophrenia Patient-Derived NRXN1-Mutant Neurons. (2021) Proc. Natl. Acad. Sci. U.S.A. 118, e2025598118. PMID: 34035170

35.  Patzke, C., Dai, J., Brockmann, M., Sun, Z., Fenske, P., Rosenmund, C., and Südhof, T.C. Cannabinoid Receptor Activation Acutely Increases Synaptic Vesicle Numbers by Activating Synapsins in Human Synapses. (2021) Mol. Psychiatry 26, 6103. PMID: 33931733

36.  Luo, F., Sclip, A., and Südhof, T.C. Neurexins regulate presynaptic GABAB-receptors at central synapses. (2021) Nat. Commun. 12, 2380. PMID: 33888718

37.  Liakath-Ali, K., and Südhof, T.C. The perils of navigating activity-dependent alternative splicing of neurexins. (2021) Front. Molec. Neurosci. 14, 659681. PMID: 33767611

38.  Sando, R., and Südhof, T.C. Latrophilin GPCR Signaling Mediates Synapse Formation. (2021) E-Life 10, e65717. PMID: 33646123

39.  Mencacci, N.E., Brockmann, M.M., Dai, J., Pajusalu, S., Atasu, B., Campos, J., Pino, G., Gonzalez-Latapi P, Patzke, C., Schwake, M., Tucci, A., Pittman, A., Simon-Sanchez ,J., Carvill, G.L., Balint, B., Wiethoff, S., Warner, T.T., Papandreou, A., Soo, A.K.S., Rein R., Kadastik-Eerme, L., Puusepp, S., Reinson, K., Tomberg, T., Hanagasi, H., Gasser, T., Bhatia, K.P., Kurian M.A., Lohmann, E., Õunap, K., Rosenmund, C., Südhof, T.C., Wood, N., Krainc, D., and Acuna, C. Bi-allelic variants in TSPOAP1, encoding the active zone protein RIMBP1, cause autosomal recessive dystonia. (2021) J. Clin. Invest. 131, e140625. PMID: 33539324

40.  Jiang, X., Sando, R., and Südhof, T.C. Multiple signaling pathways are essential for synapse formation induced by synaptic adhesion molecule. (2021) Proc. Natl. Acad. Sci. U.S.A. 118, e2000173118. PMID: 33431662

41.  Sun, Z., and Südhof, T.C. A simple Ca2+-imaging approach to neural network analysis in cultured neurons. (2021) J. Neurosci. Methods 349, 109041. PMID: 33340555

42.  Chen, M., Jiang, X., Quake, S.R., and Südhof, T.C. Persistent transcriptional programmes are associated with remote memory. (2020) Nature 587, 437-442. PMID: 33177708

43.  Gan, K., and Südhof, T.C. SPARCL1 promotes excitatory but not inhibitory synapse formation and function independent of neurexins and neuroligins. (2020) J. Neurosci. 40, 8088-8102.  PMID: 32973045

44.  Brockmann, M.M., Zarebidaki, F., Camacho, M., Grauel, M.K., Trimbuch, T.,  Südhof, T.C., and Rosenmund, C. A Trio of Active Zone Proteins Comprised of RIM-BPs, RIMs, and Munc13s Governs Neurotransmitter Release. (2020) Cell Reports 32, 107960. PMID: 32755572

45.  Khajal, A.J., Sterky, F.H., Sclip, A., Schwenk, J., Brunger, A.T., Fakler, B., and Südhof, T.C. Deorphanizing FAM19A Proteins as Pan-Neurexin Ligands with an Unusual Biosynthetic Binding Mechanism. (2020) J. Cell Biol. 219, e202004164 (selected for JCB's "Cellular Neurobiology 2020" special collection: https://rupress.org/jcb/collection/18565/Cellular-Neurobiology-2020). PMID: 32706374

46.  Zhou, M., Melin, M.D., Xu, W., and Südhof, T.C. Dysfunction of parvalbumin neurons in the cerebellar nuclei produces an action tremor. (2020) J Clin. Invest. 130, 5142-5156. PMID: 32634124

47.  Wang, C.Y., Liu, Z., Ng, Y.H., and Südhof, T.C. A synaptic circuit required for acquisition but not recall of social transmission of food preference. (2020) Neuron 107, 144-157. PMID: 32369733

48.  Li, J., Xie, Y., Cornelius, S., Jiang, X., Sando, R., Kordon, S., Pan, M., Leon, K., Südhof, T.C., Zhao, M., and Araç, D. Alternative splicing controls teneurin-latrophilin interaction and synapse specificity by a shape-shifting mechanism. (2020) Nature Comm. 11, 2140. PMID: 32358586

49.  Qian Yi Lee, Q.Y., Mall, M., Chanda, S., Zhou, B., Sharma, K.S., Schaukowitch, K., Adrian-Segarra, J.M., Grieder, S.D., Kareta, M.S., Wapinski, O.L., Ang, C.E., Li, R., Südhof, T.C., Chang, H.Y., Wernig, M. Pro-neuronal activity of Myod1 due to promiscuous binding to neuronal genes. (2020) Nature Cell Biol. 22, 401-411. PMID: 32231311

50.  Zhang, R., Liakath-Ali, K., and Südhof, T.C. Latrophilin-2 and Latrophilin-3 Are Redundantly Essential for Parallel-Fiber Synapse Function in Cerebellum. (2020) E-Life 9, pii: e54443. PMID: 32202499

51.  Luo, F., Sclip, A., Jiang, M., and Südhof, T.C. Neurexins Cluster Ca2+ Channels within presynaptic Active Zone. (2020) Neuron 75, 11-25. PMID: 32134527

52.  Maxeiner, S., Benseler, F., Krasteva-Christ, G., Brose, N., and Südhof, T.C. Evolution of the Autism-Associated Neuroligin-4 Gene Reveals Broad Erosion of Pseudoautosomal Regions in Rodents. (2020) Molecular Biology and Evolution 37, 1243-1258. PMID: 32011705

53.  Sclip, A, and Südhof, T.C. LAR receptor phospho-tyrosine phosphatases regulate NMDA-receptor responses. (2020) E-Life 9, pii: e53406. PMID: 31985401

54.  Stanley, G., Gocke, O., Malenka, R.C., Südhof, T.C., and Quake, S.R. Continuous and Discrete Neuron Types of the Adult Murine Striatum. (2019) Neuron 105, 688-699. PMID: 31813651

55.  Patzke, C., Brockmann, M.M., Dai, J., Gan, K.J., Grauel, M.K., Fenske, P., Liu, Y., Acuna, C., Rosenmund, C., and Südhof, T.C. Neuromodulator Signaling Bidirectionally Controls Vesicle Numbers in Human Synapses. (2019) Cell 179, 498-513. PMID: 31585084

56.  Wilson, S., White, K.I., Zhou, Q., Pfuetzner, R.A., Choi, U.B., Südhof, T.C., and Brunger, A.T. Structures of Neurexophilin-Neurexin Complexes Reveal a Regulatory Mechanism of Alternative Splicing. (2019) EMBO J. 38: e101603. PMID: 31566781

57.  Dong, J.X., Lee, Y., Kirmiz, M., Palacio, S., Dumitras, C., MOreno, C.M., Sando, R., Santana, F., Südhof, T.C., Gong, B., Murray, K.D., and Trimmer, J. A toolbox of nanobodies developed and validated for use as intrabodies and nanoscale immunolabels in brain neurons. (2019) E-Life 8, pii: e48750. PMID: 31566565

58.  Huang, Y.A., Zhou, B., Nabet, A.M., Wernig, M., and Südhof, T.C. Differential Signaling Mediated by ApoE2, ApoE3, and ApoE4 in Human Neurons Parallels Alzheimer's Disease Risk. (2019) J. Neurosci. 39, 7408-7427. PMID: 31331998

59.  Trotter, J.H., Hao, J., Maxeiner, S., Tsetsenis, T., Liu, Z., Zhuang, X., and Südhof ,T.C. Synaptic Neurexin-1 Assembles into Dynamically Regulated Active Zone Nanoclusters. (2019) J. Cell Biology 218, 2677-2698. PMID: 31262725

60.  Marro, S., Chanda, S., Yang, N., Janas, J.A., Valperga, G., Trotter, J.H., Zhou, B., Merrill, S., Yousif, I., Shelby, H., Vogel, H., Kalani, M.Y.S., Südhof, T.C., and Wernig, M. Neuroligin-4 regulates excitatory synaptic transmission in human neurons. (2019) Neuron 103, 617-626. PMID: 31257103

61.  Koopmans F, van Nierop P, Andres-Alonso M, Byrnes A, Cijsouw T, Coba MP, Cornelisse LN, Farrell RJ, Goldschmidt HL, Howrigan DP, Hussain NK, Imig C, de Jong APH, Jung H, Kohansalnodehi M, Kramarz B, Lipstein N, Lovering RC, MacGillavry H, Mariano V, Mi H, Ninov M, Osumi-Sutherland D, Pielot R, Smalla KH, Tang H, Tashman K, Toonen RFG, Verpelli C, Reig-Viader R, Watanabe K, van Weering J, Achsel T, Ashrafi G, Asi N, Brown TC, De Camilli P, Feuermann M, Foulger RE, Gaudet P, Joglekar A, Kanellopoulos A, Malenka R, Nicoll RA, Pulido C, de Juan-Sanz J, Sheng M, Südhof TC, Tilgner HU, Bagni C, Bayés À, Biederer T, Brose N, Chua JJE, Dieterich DC, Gundelfinger ED, Hoogenraad C, Huganir RL, Jahn R, Kaeser PS, Kim E, Kreutz MR, McPherson PS, Neale BM, O'Connor V, Posthuma D, Ryan TA, Sala C, Feng G, Hyman SE, Thomas PD, Smit AB, Verhage M. SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse. (2019) Neuron 103, 217-234. PMID: 31171447

62.  Liu, Y., Sugiura, Y., Südhof, T.C., and Lin, W. (2019) Ablation of all synaptobrevin vSNAREs blocks evoked but not spontaneous neurotransmitter release at neuromuscular synapses. (2019) J. Neurosci. 39, 6049-6066. PMID: 31160536

63.  Gan, K., and Südhof ,T.C. Specific factors in blood from young but not old mice directly promote synapse formation and NMDA-receptor recruitment. (2019) Proc. Natl. Acad. Sci. U.S.A. 116, 12524-12533. PMID: 31160442

64.  Chanda, S., Ang, C.E., Lee, Q.Y., Ghebrial, M., Haag, D., Shibuya, Y., Wernig, M., and Südhof, T.C. Direct Reprogramming of Human Neurons Identifies MARCKSL1 as a Pathogenic Mediator of Valproic Acid-Induced Teratogenicity. (2019) Cell Stem Cell 25, 103-119. PMID: 31155484

65.  Dai, J., Aoto, J., and Südhof, T.C. (2019) Alternative Splicing of Presynaptic Neurexins Differentially Controls Postsynaptic NMDA- and AMPA-Receptor Responses. (2019) Neuron 102, 993-1008. PMID: 31005376

66.  Wu, X., Morishita, W.K., Riley, A.M., Hale, W.D., Südhof, T.C., and Malenka, R.C. Neuroligin-1 Signaling Controls LTP and NMDA-Receptors by Distinct Molecular Pathway. (2019) Neuron 102, 621-635. PMID: 30871858

67.  Shimojo, M., Madara, J., Pankow, S., Liu, X., Yates, J. 3rd, Südhof, T.C., and Maximov, A. Synaptotagmin-11 mediates a vesicle trafficking pathway that is essential for development and synaptic plasticity. (2019) Genes and Dev. 33, 365-376. PMID: 30808661

68.  Sando, R., Jiang, X., and Südhof, T.C. (2019) Latrophilin GPCRs direct synapse specificity by coincident binding of FLRTs and teneurins. (2019) Science 363, pii: eaav7969. PMID: 30792275

69.  Hsu, Y.T., Li, J., Wu, D., Südhof, T.C., and Chen, L. Synaptic retinoic acid receptor signaling mediates mTOR-dependent metaplasticity that controls hippocampal learning. (2019) . Proc. Natl. Acad. Sci. U.S.A. 116, 7113-7122. PMID: 30782829

70.  Zhong, L., Chen, X., Park, E., Südhof, T.C., and Chen, L. (2018) Retinoic acid receptor RARα-dependent synaptic signaling mediates homeostatic synaptic plasticity at the inhibitory synapses of mouse visual cortex. (2018) J. Neurosci. 38, pii: 1133-1118. PMID: 30355624

71.  Zhou, M., Liu, Z., Melin, M.D., Ng, Y.H., Xu, W., and Südhof, T.C. A Central Amygdala to Zona Incerta Projection is Required for Acquisition and Remote Recall of Conditioned Fear Memory. (2018) Nature Neuroscience 21, 1515-1519. PMID: 30349111

72.  Seigneur, E., Pollepali, J., and Südhof, T.C. Cbln2 and Cbln4 are expressed in distinct medial habenula-interpeduncular projections and contribute to different behavioral outputs. (2018) Proc. Natl. Acad. Sci. U.S.A. 115, E10235-E10244. PMID: 30287486

73.  Zhang, Z., Marro, S.G., Zhang, Y., Arendt, K.L., Patzke, C., Zhou, B., Fair, T., Yang, N., Südhof, T.C., Wernig, M., and Chen, L. The fragile X mutation impairs homeostatic plasticity in human neurons by blocking synaptic retinoic acid signaling. (2018) Sci. Transl. Med. 10, pii: eaar4338. PMID: 30068571

74.  Sclip, A., Acuna, C., Luo, F., and Südhof, T.C. RIM-binding proteins recruit BK-channels to presynaptic release sites adjacent to voltage-gated Ca2+-channels. (2018) EMBO J. 37, pii: e98637. PMID: 29967030

75.  Tanabe, K., Ang, C.E., Chanda, S., Olmos, V.H., Haag, D., Levinson, D., Südhof, T.C., and Wernig, M. Trans-differentiation of human adult peripheral blood T cells into neurons. (2018) Proc. Natl. Acad. Sci. U.S.A. 115, 6470-6475. PMID: 29866841

76.  Bhouri, M., Morishita, W., Temkin, P., Goswami, D., Kawabe, H., Brose, N., Südhof, T.C., Craig, A.M., Siddiqui, T.J., and Malenka, R.C. Deletion of LRRTM1 and LRRTM2 in adult mice impairs basal AMPA receptor transmission and LTP in hippocampal CA1 pyramidal neurons. (2018) Proc. Natl. Acad. Sci. U.S.A. 115, E5382-E5389. PMID: 29784826

77.  Zhang, B., Hale, D., Brose, N., and Südhof, T.C. Autism-Associated Neuroligin-4 Mutation Selectively Impairs Glycinergic Synaptic Transmission in Mouse Brainstem Synapses. (2018) J. Exp. Medicine 215, 1543-1553. PMID: 29724786

78.  Seigneur, E., and Südhof, T. C. Genetic ablation of all cerebellins reveals synapse organizer functions in multiple regions throughout the brain. (2018) J. Neurosci. 38, 4774-4790. PMID: 29691328

79.  Li, J., Shalev-Benami, M., Sando, R., Jiang, X., Kibrom, A., Wang, J., Leon, K., Katanski, C., Nazarko, O., Lu, Y.C., Südhof, T.C., Skiniotis, G., and Araç, D. Structural basis for teneurin function in circuit-wiring: A toxin motif at the synapse. (2018) Cell 173, 735-748. PMID: 29677516

80.  Anderson, G., Maxeiner, S., Sando, R., Tsetsenis, T., Malenka, R.C., and Südhof, T.C. Postsynaptic Latrophilin-2 Mediates Target Recognition in Entorhinal-Hippocampal Synapse Assembly. (2017) J. Cell Biol. 216, 3831-3846. PMID: 28972101

81.  Voleti, R., Tomchick, D.R., Südhof, T.C., and Rizo-Rey, J. Exceptionally tight membrane-binding may explain the key role of the synaptotagmin-7 C2A domain in asynchronous neurotransmitter release. (2017) Proc. Natl. Acad. Sci. U.S.A. 114, E8518-E8527. PMID: 28923929

82.  Luo, F., Liu, X., Südhof, T. C., and Acuna, C. Efficient stimulus-secretion coupling at ribbon synapses requires RIM-binding protein tethering of L-type Ca2+ channels. (2017) Proc. Natl. Acad. Sci. U.S.A. 114, E8081-E8090. PMID: 28874522

83.  Zhou, Q., Zhou, P., Wang, A.L., Wu, D., Zhao, M., Südhof, T.C., and Brunger, A.T. The Primed SNARE-Complexin-Synaptotagmin Complex for Neuronal Exocytosis. (2017) IGF1-dependent synaptic plasticity PMID: 28813412

84.  Seigneur, E., and Südhof, T. C. Cerebellins are differentially expressed in selective subsets of neurons throughout the brain. (2017) J. Comp. Neurol. 525, 3286-3311. PMID: 28714144

85.  Liu, Z., Chen, Z., Shang, C., Yan, F., Shi, Y., Zhang, J., Qu, B., Han, H., Wang, Y., Li, D., Südhof, T.C., and Cao, P. IGF1-dependent synaptic plasticity of mitral cells encodes olfactory memory during social learning. (2017) Neuron 95, 106-122. PMID: 28683263

86.  Chanda, S., Hale, D.W., Zhang, B., Wernig, M., and Südhof, T.C. Unique versus Redundant Functions of Neuroligin Genes in Shaping Excitatory and Inhibitory Synapse Properties. (2017) J. Neurosci. 37, 6816-6836. PMID: 28607166

87.  Chew, K.S., Fernandez, D.C., Hattar, S., Südhof, T.C., and Martinelli, D.C. Anatomical and Behavioral Investigation of C1ql3 in the Mouse Suprachiasmatic Nucleus. (2017) J. Biol. Rhythms 32, 222-236. PMID: 28553739

88.  Luo, F., and Südhof, T.C. Synaptotagmin-7 Mediated Asynchronous Release Boosts High-Fidelity Synchronous Transmission at a Central Synapse. (2017) Neuron 94, 826-839. PMID: 28521135

89.  Yang, N., Chanda, S., Marro, S., Ng, Y-H., Janas, J. A., Haag, D., Ang, C.E. , Tang, Y., Flores, Q., Mall, M., Wapinski, O., Li, M., Arlenius, H., Rubenstein, J., Chang, H. Y., Alvarez-Buylla, A., Südhof, T. C., and Wernig, M. Generation of pure GABAergic neurons by transcription factor program. (2017) Nature Methods 14, 621-628. PMID: 28504679

90.  Chen, L.Y., Jiang, M., Zhang, B., Gokce, O., and Südhof, T.C. Conditional Deletion of All Neurexins Defines Diversity of Essential Synaptic Organizer Functions for Neurexins. (2017) Neuron 94, 611-625. PMID: 28472659

91.  Mall, M., Kareta, M.S., Chanda, S., Ahlenius, H., Perotti, N., Zhou, B., Grieder, S.D., Ge., X., Drake, S., Ang, D.E., Walker, B.M., Vierbuchen, T., Fuentes, D.R., Brennecke, P., Nitta, K.R., Jolma, A., Steinmetz, L.M., Taipale, J., Südhof, T.C., and Wernig, M. Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates. (2017) Nature 544, 245-249. PMID: 28379941

92.  Wu, D., Bacaj, T., Morishita, W., Goswami, D., Arendt, K.L., Xu, W., Chen, L., Malenka. R.C., and Südhof, T.C. Postsynaptic Synaptotagmins Mediate AMPA Receptor Exocytosis During LTP. (2017) Nature 544, 316-321.  PMID: 28355182

93.  Kawabe, H., Mitkovski, M., Kaeser, P.S., Hirrlinger, J., Opazo, F., Nestvogel, D., Kalla, S., Fejtova, A., Verrier, S.E., Bungers, S.R., Cooper, B.H., Varoqueaux, F., Wang, Y., Nehring, R.B., Gundelfinger, E.D., Rosenmund, C., Rizzoli, S.O., Südhof, T.C., Rhee, J.S., and Brose, N. Correction: ELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones. (2017) J. Cell Biol. 216, 1143-1161. PMID: 28289090