Nanoscale analysis of structural synaptic plasticity

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Abstract

Structural plasticity of dendritic spines and synapses is an essential mechanism to sustain long lasting changes in the brain with learning and experience. The use of electron microscopy over the last several decades has advanced our understanding of the magnitude and extent of structural plasticity at a nanoscale resolution. In particular, serial section electron microscopy (ssEM) provides accurate measurements of plasticity-related changes in synaptic size and density and distribution of key cellular resources such as polyribosomes, smooth endoplasmic reticulum, and synaptic vesicles. Careful attention to experimental and analytical approaches ensures correct interpretation of ultrastructural data and has begun to reveal the degree to which synapses undergo structural remodeling in response to physiological plasticity.

Highlights

► Serial section electron microscopy (ssEM) is a necessary tool to study plasticity. ► Multiple experimental and analytical factors must be considered when using ssEM. ► ssEM has revealed at nanometer resolution changes in synapse size and composition.

Section snippets

General principles

Successful interpretation of structural synaptic plasticity using electron microscopy requires consideration of multiple factors. Especially important are the methods of tissue preservation, experimental preparation, LTP induction, and appropriate analysis.

Sample results from ssEM that illustrate ultrastructural plasticity of synapses

Synapses are dynamic structures surrounded by a complex neuropil including dendrites, axons, and astroglial processes. Synapses within a small area of neuropil can vary greatly in their size, shape, composition of subcellular organelles and access to perisynaptic astroglial processes. All of these factors influence functional synaptic plasticity, hence it is important to identify their structural relationships accurately. Here we discuss representative examples where ssEM has served to

Conclusions

In the past 60 years, ssEM has evolved into a powerful tool with which to study the ultrastructural plasticity of synapses. Advances in technology have aided the rate at which data can be acquired and analyzed, leading to an expanding interest in mapping the neurocircuitry of the brain at the nanometer level, the so-called ‘connectome’ [82]. However, even knowing the location of every synapse in the connectome will not provide the complete answer because we need to know the functional state of

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

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References (84)

  • S.S. Zakharenko et al.

    Visualization of changes in presynaptic function during long-term synaptic plasticity

    Nat Neurosci

    (2001)
  • S.L. Morgan et al.

    Electrical stimuli patterned after the theta-rhythm induce multiple forms of LTP

    J Neurophysiol

    (2001)
  • Y. Geinisman et al.

    Structural synaptic correlate of long-term potentiation: formation of axospinous synapses with multiple, completely partitioned transmission zones

    Hippocampus

    (1993)
  • N. Toni et al.

    Remodeling of synaptic membranes after induction of long-term potentiation

    J Neurosci

    (2001)
  • K.J. Darcy et al.

    Constitutive sharing of recycling synaptic vesicles between presynaptic boutons

    Nat Neurosci

    (2006)
  • C.D. Harvey et al.

    The spread of Ras activity triggered by activation of a single dendritic spine

    Science

    (2008)
  • K. Zito et al.

    Rapid functional maturation of nascent dendritic spines

    Neuron

    (2009)
  • A. Denker et al.

    Synaptic vesicle pools: an update

    Front Synaptic Neurosci

    (2010)
  • M.E. Chicurel et al.

    Serial electron microscopy of CA3 dendritic spines synapsing with mossy fibers of rat hippocampus

    Soc Neurosci Abs

    (1989)
  • M.D. Applegate et al.

    Redistribution of synaptic vesicles during long-term potentiation in the hippocampus

    Brain Res

    (1987)
  • O. Steward et al.

    Protein synthesis at synaptic sites on dendrites

    Annu Rev Neurosci

    (2001)
  • J.R. Cooney et al.

    Endosomal compartments serve multiple hippocampal dendritic spines from a widespread rather than a local store of recycling membrane

    J Neurosci

    (2002)
  • M.E. Tremblay et al.

    Microglial interactions with synapses are modulated by visual experience

    PLoS Biol

    (2010)
  • J.W. Lichtman et al.

    Ome sweet ome: what can the genome tell us about the connectome?

    Curr Opin Neurobiol

    (2008)
  • J. Kim et al.

    Regulation of dendritic excitability by activity-dependent trafficking of the A-type K+ channel subunit Kv4.2 in hippocampal neurons

    Neuron

    (2007)
  • S.L. Palay et al.

    The fine structure of neurons

    J Biophys Biochem Cytol

    (1955)
  • E.G. Gray

    Axo-somatic and axo-dendritic synapses of the cerebral cortex: an electron microscope study

    J Anat

    (1959)
  • J.N. Bourne et al.

    Polyribosomes are increased in spines of CA1 dendrites 2 h after the induction of LTP in mature rat hippocampal slices

    Hippocampus

    (2007)
  • J.N. Bourne et al.

    Coordination of size and number of excitatory and inhibitory synapses results in a balanced structural plasticity along mature hippocampal CA1 dendrites during LTP

    Hippocampus

    (2011)
  • J.C. Fiala et al.

    Dendritic spines do not split during hippocampal LTP or maturation

    Nat Neurosci

    (2002)
  • L.E. Ostroff et al.

    Polyribosomes redistribute from dendritic shafts into spines with enlarged synapses during LTP in developing rat hippocampal slices

    Neuron

    (2002)
  • M. Park et al.

    Plasticity-induced growth of dendritic spines by exocytic trafficking from recycling endosomes

    Neuron

    (2006)
  • M.R. Witcher et al.

    Plasticity of perisynaptic astroglia during synaptogenesis in the mature rat hippocampus

    Glia

    (2007)
  • A. Holtmaat et al.

    Experience-dependent and cell-type-specific spine growth in the neocortex

    Nature

    (2006)
  • G.W. Knott et al.

    Spine growth precedes synapse formation in the adult neocortex in vivo

    Nat Neurosci

    (2006)
  • J.T. Trachtenberg et al.

    Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex

    Nature

    (2002)
  • K. Zito et al.

    Induction of spine growth and synapse formation by regulation of the spine actin cytoskeleton

    Neuron

    (2004)
  • L.E. Ostroff et al.

    Fear and safety learning differentially affect synapse size and dendritic translation in the lateral amygdala

    Proc Natl Acad Sci U S A

    (2010)
  • G.E. Sosinsky et al.

    The combination of chemical fixation procedures with high pressure freezing and freeze substitution preserves highly labile tissue ultrastructure for electron tomography applications

    J Struct Biol

    (2008)
  • P. Rostaing et al.

    Analysis of synaptic ultrastructure without fixative using high-pressure freezing and tomography

    Eur J Neurosci

    (2006)
  • R.D. Burgoyne et al.

    Depolymerization of dendritic microtubules following incubation of cortical slices

    Neurosci Lett

    (1982)
  • S. Feig et al.

    N-methyl-d-aspartate receptor activation and Ca2+ account for poor pyramidal cell structure in hippocampal slices

    J Neurochem

    (1990)

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