Synaptic development articles within Nature Communications

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• Article
  10 April 2024 | Open Access

  Complex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons

  Connecting cerebral organoids with an axon bundle models inter-regional projections and enhances neural activity. Optogenetic stimulation induces short-term plasticity, offering insights into macroscopic circuit development and functionality.

  • Tatsuya Osaki
  • , Tomoya Duenki
  •  & Yoshiho Ikeuchi

• Article
  28 March 2024 | Open Access

  Remodeling of the postsynaptic proteome in male mice and marmosets during synapse development

  The proteomic changes that occur during synapse development are not fully understood. In this work, the authors characterise the postsynaptic proteome changes that occur during development in male mice and marmosets.

  • Takeshi Kaizuka
  • , Takehiro Suzuki
  •  & Toru Takumi

• Article
  01 February 2024 | Open Access

  Neuronal DSCAM regulates the peri-synaptic localization of GLAST in Bergmann glia for functional synapse formation

  The glutamate transporter GLAST in astrocyte regulates synapse function by glutamate clearance. Here, the authors show that Down syndrome cell adhesion molecule (DSCAM) in Purkinje cells controls synaptogenesis through the intercellular association with GLAST in the developing cerebellum.

  • Ken-ichi Dewa
  • , Nariko Arimura
  •  & Mikio Hoshino

• Article
  02 January 2024 | Open Access

  Non-canonical interplay between glutamatergic NMDA and dopamine receptors shapes synaptogenesis

  Although functional interactions between receptors shape brain cell communication, their direct interaction remains elusive. Here, authors monitor the weak and transient interaction between NMDA and dopamine receptors, which tune synaptogenesis.

  • Nathan Bénac
  • , G. Ezequiel Saraceno
  •  & Laurent Groc

• Article
  18 November 2023 | Open Access

  The homeodomain transcriptional regulator DVE-1 directs a program for synapse elimination during circuit remodeling

  Synapse elimination is a critical process in the maturation of brain circuitry. Here the authors identify a key transcriptional program in Caenorhabditis elegans that directs the elimination of juvenile synapses during developmental circuit rewiring.

  • Kellianne D. Alexander
  • , Shankar Ramachandran
  •  & Michael M. Francis

• Article
  27 September 2023 | Open Access

  Celf4 controls mRNA translation underlying synaptic development in the prenatal mammalian neocortex

  While progress in early human cortical development is acknowledged, a limited understanding persists regarding transcriptomic and translational profiles in subplate neurons. Here, the authors discovered an enrichment of autism spectrum disorder risk genes in subplate neurons, underscoring the crucial role played by the RNA-binding protein CELF4 in translating synaptic mRNAs during neocortical development.

  • Iva Salamon
  • , Yongkyu Park
  •  & Mladen-Roko Rasin

• Article
  16 September 2023 | Open Access

  Loss of microglial MCT4 leads to defective synaptic pruning and anxiety-like behavior in mice

  The role of lactate in the control of microglial function remains poorly investigated. Here, the authors show that lactate promotes lysosomal acidification in microglia, and that mice lacking the lactate transporter MCT4 in these cells display defective brain development and anxiety-like behavior.

  • Katia Monsorno
  • , Kyllian Ginggen
  •  & Rosa Chiara Paolicelli

• Article
  17 August 2023 | Open Access

  Combinatorial expression of neurexins and LAR-type phosphotyrosine phosphatase receptors instructs assembly of a cerebellar circuit

  Whether presynaptic ‘hub’ adhesion molecules are essential for synapse formation is still unclear. Here, the authors generate sextuple conditional knockout mice that target Neurexins and LAR-PTPRs and find that their combinatorial expression instructs the assembly of a cerebellar circuit.

  • Alessandra Sclip
  •  & Thomas C. Südhof

• Article
  24 June 2023 | Open Access

  Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids

  Copy number deletions in 2p16.3 locus (NRXN1) in individuals significantly increase risk for schizophrenia. Here, authors show, at single cell level, genetic background-specific effects that culminate in synaptic dysfunction using iPSC-derived brain organoid model.

  • Rebecca Sebastian
  • , Kang Jin
  •  & ChangHui Pak

• Article
  02 June 2023 | Open Access

  Circadian regulation of developmental synaptogenesis via the hypocretinergic system

  Whether the circadian clock regulates early developmental processes is poorly understood. Here, the authors report the circadian rhythm of synapse formation during early brain development by using the retinotectal system of larval zebrafish as an in vivo model.

  • Xu-Fei Du
  • , Fu-Ning Li
  •  & Jiu-Lin Du

• Article
  11 November 2022 | Open Access

  Developmental disruption and restoration of brain synaptome architecture in the murine Pax6 neurodevelopmental disease model

  Brain-wide mapping of synapse molecular composition in Pax6 mutant mice shows remodelling and restoration of synaptome architecture during development, a possible means of conferring resilience to genetic disorders.

  • Laura Tomas-Roca
  • , Zhen Qiu
  •  & Seth G. N. Grant

• Article
  08 November 2021 | Open Access

  Dopamine D2 receptor regulates cortical synaptic pruning in rodents

  Synaptic pruning is important during development and synaptic plasticity. Here, the authors show that the dopamine D2 receptor (Drd2) in the anterior cingulate cortex regulates synaptic pruning, affecting LTD and behaviour in transgenic rats.

  • Ya-Qiang Zhang
  • , Wei-Peng Lin
  •  & Dong-Min Yin

• Article
  08 October 2021 | Open Access

  In situ and transcriptomic identification of microglia in synapse-rich regions of the developing zebrafish brain

  Microglia remodel synapses and engulf apoptotic cells. The molecular program underlying these distinct functions are unclear. Here, the authors identify distinct microglial subsets associated with synaptic vs. neurogenic regions of the developing zebrafish brain.

  • Nicholas J. Silva
  • , Leah C. Dorman
  •  & Anna V. Molofsky

• Article
  15 September 2021 | Open Access

  Functional and molecular characterization of a non-human primate model of autism spectrum disorder shows similarity with the human disease

  Non-human primate models of autism spectrum disorder (ASD) are few and not well characterised. Here, the authors describe synaptic function and gene expression changes in a marmoset model of ASD from birth to juvenile, highlighting its similarity to features observed in human ASD.

  • Satoshi Watanabe
  • , Tohru Kurotani
  •  & Noritaka Ichinohe

• Article
  26 August 2021 | Open Access

  Oligodendrocytic Na⁺-K⁺-Cl^– co-transporter 1 activity facilitates axonal conduction and restores plasticity in the adult mouse brain

  Brain plasticity declines with age. Here, the authors show that NKCC1 regulates oligodendrocyte activity, facilitating neuronal plasticity during juvenile. Inducing activation of oligodendrocytic NKCC1 results in restoration of neuronal plasticity in the adult mouse brain.

  • Yoshihiko Yamazaki
  • , Yoshifumi Abe
  •  & Kenji F. Tanaka

• Article
  01 April 2021 | Open Access

  Loss of microglial SIRPα promotes synaptic pruning in preclinical models of neurodegeneration

  Microglial SIRPα regulates synaptic pruning during development. Its role in neurodegeneration is unclear. Here, the authors show microglial SIRPα declines in the model of Alzheimer’s disease, leading to excessive microglia mediated synapse elimination as well as impaired cognitive function.

  • Xin Ding
  • , Jin Wang
  •  & Liang Li

• Article
  14 October 2020 | Open Access

  Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer

  Mossy fiber synapses are key in CA3 microcircuit function. Here, the authors profile the mossy fiber synapse proteome and cell-surface interactome. They uncover a diverse repertoire of cell-surface proteins and identify the receptor IgSF8 as a regulator of CA3 microcircuit connectivity and function.

  • Nuno Apóstolo
  • , Samuel N. Smukowski
  •  & Joris de Wit

• Article
  31 January 2020 | Open Access

  Structural insights into selective interaction between type IIa receptor protein tyrosine phosphatases and Liprin-α

  Synaptic organizers are cell-adhesion molecules capable of inducing synaptic differentiation through transsynaptic interactions. Here the authors present the crystal structure of the intracellular interaction between the synaptic organizer PTPδ and Liprin-α to reveal the structural mechanism of intracellular molecular interactions for IIa-RPTP-mediated synapse formation.

  • Maiko Wakita
  • , Atsushi Yamagata
  •  & Shuya Fukai

• Article
  29 January 2020 | Open Access

  Positive surface charge of GluN1 N-terminus mediates the direct interaction with EphB2 and NMDAR mobility

  NMDA receptors undergo constant cycling into and out of the postsynaptic density. Here authors show that NMDAR's GluN1 subunit is required to maintain NMDARs at dendritic spine synapses by direct extracellular interaction with the receptor tyrosine kinase EphB2.

  • Halley R. Washburn
  • , Nan L. Xia
  •  & Matthew B. Dalva

• Article
  06 December 2019 | Open Access

  The calcium channel subunit α₂δ-3 organizes synapses via an activity-dependent and autocrine BMP signaling pathway

  Activity-dependent pathways are important for synapse function but the molecular links to synapse function are not clear. The authors show that the Ca²⁺ channel subunit α₂δ-3 provides an extracellular scaffold for autocrine BMP signalling at the Drosophila neuromuscular junction.

  • Kendall M. Hoover
  • , Scott J. Gratz
  •  & Heather T. Broihier

• Article
  12 July 2019 | Open Access

  AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders

  Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca²⁺ transport and AMPAR currents.”

  • Vincenzo Salpietro
  • , Christine L. Dixon
  •  & Henry Houlden

• Article
  08 February 2019 | Open Access

  BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis

  BMP ligands act as retrograde signalling molecules to regulate presynaptic development, and regulation of BMP receptors by endocytosis may be an important component of this signalling pathway. Here, the authors show that Abi-mediated macropinocytosis of BMP receptors in Drosophila larva and contributes to neuromuscular development.

  • Najin Kim
  • , Sungdae Kim
  •  & Seungbok Lee

• Article
  28 September 2018 | Open Access

  A unique intracellular tyrosine in neuroligin-1 regulates AMPA receptor recruitment during synapse differentiation and potentiation

  Neuroligins are postsynaptic cell adhesion molecules thought to play roles in synaptic development and function. Here, authors show that phosphorylation of Y782 in neuroligin-1 modulates its role in differentiation and ability to recruit AMPARs including during long-term potentiation.

  • Mathieu Letellier
  • , Zsófia Szíber
  •  & Olivier Thoumine

• Article
  22 August 2018 | Open Access

  Experience-dependent structural plasticity targets dynamic filopodia in regulating dendrite maturation and synaptogenesis

  During development, dendrites display structural plasticity, as reflected in the appearance of long, thin and highly motile dendritic filopodia. Here, the authors examine dendritic dynamics of ventral lateral neurons in the developing Drosophila larva, and identify Amphiphysin as an important regulator of this process.

  • Chengyu Sheng
  • , Uzma Javed
  •  & Quan Yuan

• Article
  07 August 2018 | Open Access

  Developmental seizures and mortality result from reducing GABA_A receptor α2-subunit interaction with collybistin

  The inhibitory synaptic protein collybistin (CB) and GABA_AR-α subunits are thought to interact, but strength and specificity are unclear. Here the authors study the CB–α2 interaction and show that a mouse mutated in the CB-binding region of α2 displays a loss of specific synapses and seizure.

  • Rochelle M. Hines
  • , Hans Michael Maric
  •  & Stephen J. Moss

• Article
  19 July 2018 | Open Access

  Microglia permit climbing fiber elimination by promoting GABAergic inhibition in the developing cerebellum

  In the mammalian cerebellum, surplus synapses between climbing fibers (CF) and Purkinje cells (PC) are developmentally pruned. Here, Nakayama and colleagues show that ablation of microglia impairs pruning of CF-PC synapses because of dysfunction of GABAergic inhibition prerequisite for pruning.

  • Hisako Nakayama
  • , Manabu Abe
  •  & Kouichi Hashimoto

• Article
  26 March 2018 | Open Access

  Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction

  Direct visualization of microglia-mediated synapse pruning has been lacking. This study shows direct evidence of microglia-synapse interaction where microglia do not necessarily ‘eat’ post-synaptic structure but ‘nibble’ on pre-synaptic terminals, much akin to trogocytosis by lymphocytes.

  • Laetitia Weinhard
  • , Giulia di Bartolomei
  •  & Cornelius T. Gross

• Article
  02 November 2017 | Open Access

  RNF8/UBC13 ubiquitin signaling suppresses synapse formation in the mammalian brain

  Ubiquitin ligases play critical roles in neuronal connectivity in the brain. Here, Valnegri and colleagues show that ubiquitin ligase RNF8 and ubiquitin-conjugating enzyme UBC13 regulate synapse number in cerebellar granule neurons and rodent cerebellar learning.

  • Pamela Valnegri
  • , Ju Huang
  •  & Azad Bonni

• Article
  31 October 2017 | Open Access

  Homeostatic plasticity shapes the visual system’s first synapse

  Retinal rod bipolar cells (RBCs) partially undergo programmed cell death triggering cell density-dependent plasticity. This study shows that increased removal of RBCs using genetic approaches causes dendrites of the remaining RBCs to expand and contact more rod photoreceptors while reducing connectivity with each.

  • Robert E. Johnson
  • , Nai-Wen Tien
  •  & Daniel Kerschensteiner

• Article
  04 August 2017 | Open Access

  Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum

  During development, synapses are selectively strengthened or eliminated by activity-dependent competition. Here, the authors show that BDNF-TrkB retrograde signaling is a “punishment” signal that leads to elimination of climbing fiber-onto-Purkinje cell synapses in the developing cerebellum.

  • Myeongjeong Choo
  • , Taisuke Miyazaki
  •  & Masanobu Kano

• Article
  09 November 2016 | Open Access

  Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function

  Glutamatergic signalling regulation by Syngap1 has been linked to intellectual disabilities. Here, the authors find Syngap1 also regulates cortical GABAergic synaptic signalling development and that this reduced inhibitory signalling contributes to cognitive deficits in a mouse model.

  • Martin H. Berryer
  • , Bidisha Chattopadhyaya
  •  & Graziella Di Cristo

• Article
  31 October 2016 | Open Access

  Spontaneous emergence of fast attractor dynamics in a model of developing primary visual cortex

  Sensory cortices represent stimuli through joint activity of competing neuronal assemblies. Here the authors show that a model of visual cortex with plastic feedforward and recurrent synapses, exposed to natural images, spontaneously develops attractor dynamics between groups of similarly tuned neurons.

  • Thomas Miconi
  • , Jeffrey L. McKinstry
  •  & Gerald M. Edelman

• Article
  09 September 2016 | Open Access

  Pten and EphB4 regulate the establishment of perisomatic inhibition in mouse visual cortex

  Fast spiking interneurons provide perisomatic inhibition in the cortex. Here, Baohan et al. show the failure to develop perisomatic inhibition in heterozygous PTENnull mutant mouse and the underlying mechanism to EphB4 reduction in an experience-dependent manner.

  • Amy Baohan
  • , Taruna Ikrar
  •  & Joshua T. Trachtenberg

• Article
  25 August 2016 | Open Access

  Microglia contact induces synapse formation in developing somatosensory cortex

  Microglia contribute to shaping neural circuits in the developing brain. Here, the authors show that microglial contact with pyramidal neuron dendrites induces synapse formation in the developing somatosensory cortex, and ablation of microglia reduces synaptic connections from L4 to L2/3 neurons.

  • Akiko Miyamoto
  • , Hiroaki Wake
  •  & Junichi Nabekura

• Article
  02 August 2016 | Open Access

  SALM4 suppresses excitatory synapse development by cis-inhibiting trans-synaptic SALM3–LAR adhesion

  Synaptic adhesion molecules regulate synapse development and function by both cis and trans-interactions. Here, Lie et al. show that postsynaptic SALM4 regulates excitatory synapse numbers by cisinhibition of the SALM3-LAR transynaptic interaction.

  • Eunkyung Lie
  • , Ji Seung Ko
  •  & Eunjoon Kim

• Article
  27 April 2016 | Open Access

  NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation

  NMDARs and MAGUK proteins are capable of forming higher-order protein assemblies, however their organisation in the intact brain is unclear. Here, Frank et al. identify mouse and human supercomplexes and discover their mechanism of assembly using genetic tagging and affinity purification.

  • René A. W. Frank
  • , Noboru H. Komiyama
  •  & Seth G. N. Grant

• Article
  03 February 2016 | Open Access

  Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders

  The molecular mechanisms of neurotrophin receptor trafficking are only partially understood. Here the authors show that ARHGAP33 interacts with SORT1 to regulate TrkB trafficking, the dysfunction of which impairs synapse development and leads to schizophrenia-related behavioural abnormalities in mice.

  • Takanobu Nakazawa
  • , Ryota Hashimoto
  •  & Masanobu Kano

• Article
  11 December 2015 | Open Access

  Interneuronal DISC1 regulates NRG1-ErbB4 signalling and excitatory–inhibitory synapse formation in the mature cortex

  Neuregulin-1 and DISC1 signalling pathways have both been linked to neurodevelopment and schizophrenia. Here, Seshadri et al. demonstrate that DISC1 negatively regulates NRG1-induced ErbB4 signalling in adult cortical interneurons both in vitro and in vivo, possibly via competitive binding to PSD95.

  • Saurav Seshadri
  • , Travis Faust
  •  & Akira Sawa

• Article
  24 April 2015 | Open Access

  Mechanisms of splicing-dependent trans-synaptic adhesion by PTPδ–IL1RAPL1/IL-1RAcP for synaptic differentiation

  Synapse formation depends on trans-synaptic interactions between selective pairs of pre- and postsynaptic adhesion molecules. Here, the authors establish the basis for the splice isoform-dependent selectivity of receptor protein tyrosine phosphatase δ as it forms trans-synaptic contacts with IL1RAPL1 and IL-1RAcP.

  • Atsushi Yamagata
  • , Tomoyuki Yoshida
  •  & Shuya Fukai

• Article | 16 April 2015

  Rheb activation disrupts spine synapse formation through accumulation of syntenin in tuberous sclerosis complex

  Tuberous sclerosis complex (TSC) arises from mutations in an activator of the small GTPase Rheb. Here the authors show that syntenin binds to GDP-bound Rheb, and loss of this interaction in TSC leads to increased syntenin expression and downstream signalling defects leading to aberrant spine synapse morphogenesis.

  • Hiroko Sugiura
  • , Shin Yasuda
  •  & Kanato Yamagata

• Article | 19 February 2015

  In vivo odourant response properties of migrating adult-born neurons in the mouse olfactory bulb

  Juxtaglomerular neurons (JGNs) of the mammalian olfactory bulb are generated throughout life, but when and how these adult-born cells acquire responsiveness to sensory stimuli remains unknown. Here, the authors use in vivotwo-photon imaging to monitor the migration and integration of adult-born JGNs and their sensory response properties.

  • Yury Kovalchuk
  • , Ryota Homma
  •  & Olga Garaschuk

• Article | 14 November 2014

  Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion

  The presynaptic LAR-RPTPs interact with postsynaptic Slitrks and this contributes to regulating synapse formation. Here, the authors identified the minimal binding regions and determined the crystal structure of the resulting complex and performed functional analysis in cells to determine LAR-RPTP/Slitrk complex-mediated synapse formation.

  • Ji Won Um
  • , Kee Hun Kim
  •  & Ho Min Kim

• Article
  11 November 2014 | Open Access

  Structural basis for extracellular cis and trans RPTPσ signal competition in synaptogenesis

  Receptor protein tyrosine phosphatase sigma (RPTPσ) promotes both neurite outgrowth and synaptic organization. Here, Coles et al.present the structural basis for this switch in function, whereby TrkC on the postsynaptic membrane and heparan sulphate proteoglycans compete for the same binding surface on RPTPσ.

  • Charlotte H. Coles
  • , Nikolaos Mitakidis
  •  & A. Radu Aricescu

• Article | 12 August 2013

  Micropatterned substrates coated with neuronal adhesion molecules for high-content study of synapse formation

  Synapse formation and function studies are routinely carried out with suboptimal assays. Czöndör et al. describe a method that allows spatial control of synaptic differentiation by culturing neurons on micropatterned substrates comprising arrays of individual microdots coated with different proteins.

  • Katalin Czöndör
  • , Mikael Garcia
  •  & Olivier Thoumine

• Article | 05 August 2013

  DPP6 regulation of dendritic morphogenesis impacts hippocampal synaptic development

  Dipeptidyl-peptidase 6 is implicated in different neuropsychiatric pathologies. Lin and colleagues genetically delete dipeptidyl-peptidase 6 in mice and find that this results in impaired development of dendritic filopodia, as well as a reduction in the dendritic tree size, spine density and functional synapses.

  • Lin Lin
  • , Wei Sun
  •  & Dax A. Hoffman

• Article
  22 November 2011 | Open Access

  Dendritic spine formation and synaptic function require neurobeachin

  Most excitatory synapses in the brain are found on dendritic spines, but the mechanisms underlying synapse formation are poorly understood. Niesmannet al. investigate the role of neurobeachin in synaptogenesis, and find that its deletion leads to fewer spinous synapses and altered postsynaptic currents.

  • Katharina Niesmann
  • , Dorothee Breuer
  •  & Markus Missler

• Article | 25 October 2011

  Synapse microarray identification of small molecules that enhance synaptogenesis

  Large scale synapse assays can facilitate identification of drug leads. Shiet al. develop a 'synapse microarray' technology that enables sensitive, high-throughput, quantitative screening of synaptogenic events, and use it to identify novel histone deacetylase inhibitors that enhance synaptogenesis.

  • Peng Shi
  • , Mark A. Scott
  •  & Mehmet Fatih Yanik