Fluorescence imaging of synapse dynamics in normal circuit maturation and in developmental disorders

One of the most fundamental questions in neurobiology is how proper synaptic connections are established in the developing brain. Live-cell imaging of the synaptic structure and functional molecules can reveal the time course of synapse formation, molecular dynamics, and functional maturation. Using postsynaptic scaffolding proteins as a marker of synapse development, fluorescence time-lapse imaging revealed rapid formation of individual synapses that occurred within hours and their remodeling in culture preparations. In vivo two-photon excitation microscopy development enabled us to directly measure synapse turnover in living animals. In vivo synapse dynamics were suppressed in the adult rodent brain, but were maintained at a high level during the early postnatal period. This transition in synapse dynamics is biologically important and can be linked to the pathology of juvenile-onset psychiatric diseases. Indeed, the upregulation of synapse dynamics was observed in multiple mouse models of autism spectrum disorders. Fluorescence imaging of synapses provides new information regarding the physiology and pathology of neural circuit construction.

• Publication year

  2017

• Venue

  Proceedings of the Japan Academy. Series B, Physical and biological sciences

• Publication date

  2017-08-02

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.2183/pjab.93.029PMID 28769018PMCID 5713177
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Rho GTPase complementation underlies BDNF-dependent homo- and heterosynaptic plasticity

  2016cited by this paper
• De novo synaptogenesis induced by GABA in the developing mouse cortex

  2016cited by this paper
• Random-access scanning microscopy for 3D imaging in awake behaving animals

  2016cited by this paper
• A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging

  2016cited by this paper
• Protein kinase D promotes plasticity-induced F-actin stabilization in dendritic spines and regulates memory formation

  2015cited by this paper
• From the genetic architecture to synaptic plasticity in autism spectrum disorder

  2015cited by this paper
• Syngap1 haploinsufficiency damages a postnatal critical period of pyramidal cell structural maturation linked to cortical circuit assembly.

  2015cited by this paper
• Glutamate-induced AMPA receptor desensitization increases their mobility and modulates short-term plasticity through unbinding from Stargazin.

  2015cited by this paper
• Enhanced synapse remodelling as a common phenotype in mouse models of autism

  2014cited by this paper
• The WAVE regulatory complex links diverse receptors to the actin cytoskeleton.

  2014cited by this paper
• The Relationship between PSD-95 Clustering and Spine Stability In Vivo

  2014cited by this paper
• Nanoscale segregation of actin nucleation and elongation factors determines dendritic spine protrusion

  2014cited by this paper
• Retrograde Signaling for Climbing Fiber Synapse Elimination

  2014cited by this paper
• Two-photon excitation improves multifocal structured illumination microscopy in thick scattering tissue

  2014cited by this paper
• Dendritic spines: the locus of structural and functional plasticity.

  2014cited by this paper
• Spine neck plasticity regulates compartmentalization of synapses

  2014cited by this paper
• Pyramidal cell development: postnatal spinogenesis, dendritic growth, axon growth, and electrophysiology

  2014cited by this paper
• Fluorescence imaging of synapse formation and remodeling.

  2013cited by this paper
• The genetic landscapes of autism spectrum disorders.

  2013cited by this paper
• In vivo imaging of the developing neuromuscular junction in neonatal mice.

  2012cited by this paper
• Elimination of inhibitory synapses is a major component of adult ocular dominance plasticity.

  2012cited by this paper
• Clustered dynamics of inhibitory synapses and dendritic spines in the adult neocortex.

  2012cited by this paper
• LIS1-dependent retrograde translocation of excitatory synapses in developing interneuron dendrites

  2012cited by this paper
• Glutamate induces de novo growth of functional spines in developing cortex

  2011cited by this paper
• Inhibitory Synapse Dynamics: Coordinated Presynaptic and Postsynaptic Mobility and the Major Contribution of Recycled Vesicles to New Synapse Formation

  2011cited by this paper
• Long-term changes of spine dynamics and microglia after transient peripheral immune response triggered by LPS in vivo

  2011cited by this paper
• Dendritic spine pathology in neuropsychiatric disorders

  2011cited by this paper
• Delayed Stabilization of Dendritic Spines in Fragile X Mice

  2010cited by this paper
• Thinned-skull cranial window technique for long-term imaging of the cortex in live mice

  2010cited by this paper
• Superresolution imaging of chemical synapses in the brain.

  2010cited by this paper
• Actin in dendritic spines: connecting dynamics to function

  2010cited by this paper
• Dendritic spine instability and insensitivity to modulation by sensory experience in a mouse model of fragile X syndrome

  2010cited by this paper
• Spinogenesis and Pruning Scales across Functional Hierarchies

  2009cited by this paper
• Abnormal Behavior in a Chromosome- Engineered Mouse Model for Human 15q11-13 Duplication Seen in Autism

  2009cited by this paper
• Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window

  2009cited by this paper
• AMPA receptor incorporation into synapses during LTP: the role of lateral movement and exocytosis.

  2009cited by this paper
• Stably maintained dendritic spines are associated with lifelong memories

  2009cited by this paper
• Rapid formation and selective stabilization of synapses for enduring motor memories

  2009cited by this paper
• Serial Section Scanning Electron Microscopy of Adult Brain Tissue Using Focused Ion Beam Milling

  2008cited by this paper
• Spine Neck Plasticity Controls Postsynaptic Calcium Signals through Electrical Compartmentalization

  2008cited by this paper
• Autism‐like behavioral phenotypes in BTBR T+tf/J mice

  2008cited by this paper
• Autism: many genes, common pathways?

  2008cited by this paper
• Molecular anatomy of the postsynaptic density.

  2007cited by this paper
• A Neuroligin-3 Mutation Implicated in Autism Increases Inhibitory Synaptic Transmission in Mice

  2007cited by this paper
• Choice of cranial window type for in vivo imaging affects dendritic spine turnover in the cortex

  2007cited by this paper
• Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system

  2007cited by this paper
• Rapid Redistribution of Synaptic PSD-95 in the Neocortex In Vivo

  2006cited by this paper
• Differential Control of Postsynaptic Density Scaffolds via Actin-Dependent and -Independent Mechanisms

  2006cited by this paper
• Hebbian LTP in feed-forward inhibitory interneurons and the temporal fidelity of input discrimination

  2005cited by this paper
• Deep tissue two-photon microscopy

  2005cited by this paper
• Determination of absolute protein numbers in single synapses by a GFP-based calibration technique

  2005cited by this paper
• ReportDevelopment of Long-Term Dendritic Spine Stability in Diverse Regions of Cerebral Cortex

  2005cited by this paper
• Genesis of dendritic spines: insights from ultrastructural and imaging studies

  2004cited by this paper
• Structural basis of long-term potentiation in single dendritic spines

  2004cited by this paper
• PDZ domain proteins of synapses

  2004cited by this paper
• Synchronized Formation and Remodeling of Postsynaptic Densities: Long-Term Visualization of Hippocampal Neurons Expressing Postsynaptic Density Proteins Tagged with Green Fluorescent Protein

  2003cited by this paper
• Synaptogenesis in the CNS: An Odyssey from Wiring Together to Firing Together

  2003cited by this paper
• Calcium microdomains in aspiny dendrites.

  2003cited by this paper
• Interaction of transmembrane AMPA receptor regulatory proteins with multiple membrane associated guanylate kinases.

  2003cited by this paper
• Knowing a nascent synapse when you see it.

  2002cited by this paper
• Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex

  2002cited by this paper
• Long-term dendritic spine stability in the adult cortex

  2002cited by this paper
• Spine Formation and Correlated Assembly of Presynaptic and Postsynaptic Molecules

  2001cited by this paper
• Rapid Redistribution of the Postsynaptic Density Protein PSD-Zip45 (Homer 1c) and Its Differential Regulation by NMDA Receptors and Calcium Channels

  2001cited by this paper
• Rapid formation and remodeling of postsynaptic densities in developing dendrites

  2001cited by this paper
• Assembly of new individual excitatory synapses: time course and temporal order of synaptic molecule recruitment.

  2000cited by this paper
• Assembly of presynaptic active zones from cytoplasmic transport packets

  2000cited by this paper
• Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines

  2000cited by this paper
• Alternative Splicing of the C-Terminal Domain Regulates Cell Surface Expression of the NMDA Receptor NR1 Subunit

  1999cited by this paper
• Continual remodeling of postsynaptic density and its regulation by synaptic activity

  1999cited by this paper
• Molecular determinants for subcellular localization of PSD-95 with an interacting K+ channel.

  1999cited by this paper
• Development of the vertebrate neuromuscular junction.

  1999cited by this paper
• Molecular Determinants for Subcellular Localization of PSD-95 with an Interacting K Channel

  1999cited by this paper
• Synaptic targeting of the postsynaptic density protein PSD-95 mediated by lipid and protein motifs.

  1999cited by this paper
• Regional differences in synaptogenesis in human cerebral cortex

  1997cited by this paper
• Enlightening the Postsynaptic Density Review

  1997cited by this paper
• Binding of neuroligins to PSD-95.

  1997cited by this paper
• Reproductive toxicology. Methyl salicylate.

  1997cited by this paper
• Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95.

  1995cited by this paper
• Optimized survival of hippocampal neurons in B27‐supplemented neurobasal™, a new serum‐free medium combination

  1993cited by this paper
• The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein.

  1992cited by this paper
• Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation [published erratum appears in J Neurosci 1992 Aug;12(8):following table of contents]

  1992cited by this paper
• Rat hippocampal neurons in dispersed cell culture.

  1977cited by this paper

• Neuroligin-1 mediates presynaptic maturation through brain-derived neurotrophic factor signaling

  2021cites this paper
• Make Life Visible

  2020cites this paper
• Transgenic models for investigating the nervous system: Currently available neurofluorescent reporters and potential neuronal markers.

  2020cites this paper
• Recent advances in computational methods for measurement of dendritic spines imaged by light microscopy.

  2020cites this paper
• Single-dose ethanol intoxication causes acute and lasting neuronal changes in the brain

  2020cites this paper
• Regulation of actin dynamics in dendritic spines: nanostructure, molecular mobility, and signaling mechanisms.

  2020cites this paper
• Dynamic assembly of ribbon synapses and circuit maintenance in a vertebrate sensory system

  2019cites this paper
• Imaging Synapse Formation and Remodeling In Vitro and In Vivo

  2019cites this paper
• and Remodeling In Vitro and In Vivo

  2019cites this paper
• Nano-scale analysis of synapse morphology in an autism mouse model with 15q11-13 copy number variation using focused ion beam milling and scanning electron microscopy.

  2018cites this paper