Structure–stability–function relationships of dendritic spines

https://doi.org/10.1016/S0166-2236(03)00162-0Get rights and content

Abstract

Dendritic spines, which receive most of the excitatory synaptic input in the cerebral cortex, are heterogeneous with regard to their structure, stability and function. Spines with large heads are stable, express large numbers of AMPA-type glutamate receptors, and contribute to strong synaptic connections. By contrast, spines with small heads are motile and unstable and contribute to weak or silent synaptic connections. Their structure–stability–function relationships suggest that large and small spines are ‘memory spines’ and ‘learning spines’, respectively. Given that turnover of glutamate receptors is rapid, spine structure and the underlying organization of the actin cytoskeleton are likely to be major determinants of fast synaptic transmission and, therefore, are likely to provide a physical basis for memory in cortical neuronal networks. Characterization of supramolecular complexes responsible for synaptic memory and learning is key to the understanding of brain function and disease.

Section snippets

Spine structure and stability

Many ultrastructural investigations have described morphological changes in neurons that accompany neuronal activity. In particular, increases in the number [4] or volume [5] of dendritic spines or changes in spine shape [6] have been observed. It is not possible, however, to study the stability and function of such plasticity by electron microscopy. Recent progress in two-photon excitation imaging has, thus, been largely responsible for the demonstration that the structure of central synapses

Glutamate application with a femtosecond-pulse laser

Investigation of the function of individual spines requires the systematic application of glutamate to identifiable spines along a dendrite. Such studies have been impossible with methodologies that rely only on microelectrodes because brain tissue is too compact to allow the arbitrary movement of an electrode with a resolution at the micrometer level (Fig. 1c). The light-induced release of glutamate from caged compounds was, therefore, applied as a solution to this problem. The spatial

Spine structure and function

Matsuzaki et al. attempted to measure glutamate sensitivity at the surface of dendrites of CA1 pyramidal neurons in fresh slice preparations obtained from the rat hippocampus [22]. The two-photon uncaging of MNI-glutamate was induced at 1064 points in a cubic region encompassing a small portion of a dendrite (Fig. 1f). Sampling points were pseudo-randomized to minimize receptor desensitization. The glutamate-induced currents were recorded at the soma, and their peak amplitudes were displayed by

Memory density

Given that glutamate-mediated synaptic transmission depends on a diffusible molecule, the length of glutamate action is a crucial determinant of the practical density of synaptic connections. The length of glutamate action is, in turn, dependent on the gating properties of postsynaptic AMPA receptors. If the activation of AMPA receptors is slow, then glutamate released from a presynaptic terminal will reach neighboring synapses before the corresponding postsynaptic receptors are activated. Such

Implications of structure–stability–function relationships of spines

In memory devices, memory storage and readout occur in two different operational modes. New memory thus cannot be stored in the readout mode. By contrast, storage and readout of memory occur by inseparable processes in the brain. This feature has been a major theme for the operation of realistic neuronal networks and it has been ascribed mainly to the highly distributed nature of memory in neuronal networks and in the superposition of memories, distributed over many synapses or ‘weights’, as in

Molecular basis of spine structure–stability–function relationships

The trafficking and turnover of AMPA receptors are rapid 24, 37, 38, 39, 40 and have been proposed to account for the changes in synaptic strength during LTP [41] and LTD [42]. By contrast, given that AMPA-receptor expression is dynamically regulated in spines, the maintenance of memory must depend on stable factors that regulate AMPA-receptor expression; otherwise, the strength of synaptic connections could not be maintained in the long term. Such factors might include spine shape and the

Recapitulation

Recent progress in biophysical techniques and molecular biology has provided insight into the structure–function relationships of dendritic spines in the cerebral cortex, as well as support for the century-old hypothesis that spine structure is the basis for memory in the brain. The structure–stability–function relationships of spines have further suggested that small and large spines play distinct roles in learning and memory, enabling rapid acquisition of new memory and robust readout,

Acknowledgements

We thank Y. Hata for critical reading of the manuscript. Our work was supported by Grants-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology and from the Japan Society for the Promotion of Science, and by a research grant from the Human Frontier Science Program Organization.

References (95)

  • F. Crick

    Do dendritic spines twitch?

    Trends Neurosci.

    (1982)
  • E. Fifkova

    Actin in the nervous system

    Brain Res.

    (1985)
  • T.D. Pollard et al.

    Cellular motility driven by assembly and disassembly of actin filaments

    Cell

    (2003)
  • M. Segal

    Dendritic spine formation and pruning: common cellular mechanisms?

    Trends Neurosci.

    (2000)
  • B. Bardoni et al.

    Advances in understanding of fragile X pathogenesis and FMRP function, and in identification of X linked mental retardation genes

    Curr. Opin. Genet. Dev.

    (2002)
  • Y. Meng

    Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice

    Neuron

    (2002)
  • S. Naisbitt

    Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin

    Neuron

    (1999)
  • K. Shen

    CaMKIIβ functions as an F-actin targeting module that localizes CaMKIIα/β heterooligomers to dendritic spines

    Neuron

    (1998)
  • D.T. Pak

    Regulation of dendritic spine morphology by SPAR, a PSD-95-associated RapGAP

    Neuron

    (2001)
  • P. Penzes

    Rapid induction of dendritic spine morphogenesis by trans-synaptic EphrinB–EphB receptor activation of the Rho-GEF Kalirin

    Neuron

    (2003)
  • L.C. Hsieh-Wilson

    Phosphorylation of spinophilin modulates its interaction with actin filaments

    J. Biol. Chem.

    (2003)
  • H. Togashi

    Cadherin regulates dendritic spine morphogenesis

    Neuron

    (2002)
  • P. Scheiffele

    Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons

    Cell

    (2000)
  • I.M. Ethell

    EphB/syndecan-2 signaling in dendritic spine morphogenesis

    Neuron

    (2001)
  • L.E. Ostroff

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

    Neuron

    (2002)
  • S. Miller

    Disruption of dendritic translation of CaMKIIα impairs stabilization of synaptic plasticity and memory consolidation

    Neuron

    (2002)
  • J.E. Lisman et al.

    A model of synaptic memory: a CaMKII/PP1 switch that potentiates transmission by organizing an AMPA receptor anchoring assembly

    Neuron

    (2001)
  • S.G. Grant et al.

    Proteomics of multiprotein complexes: answering fundamental questions in neuroscience

    Trends Biotechnol.

    (2001)
  • L.R. Squire

    Memory and Brain

    (1987)
  • G.M. Shepherd

    The dendritic spine: a multifunctional integrative unit

    J. Neurophysiol.

    (1996)
  • M.B. Moser

    An increase in dendritic spine density on hippocampal CA1 pyramidal cells following spatial learning in adult rats suggests the formation of new synapses

    Proc. Natl. Acad. Sci. U. S. A.

    (1994)
  • E. Fifkova

    A possible mechanism of morphometric changes in dendritic spines induced by stimulation

    Cell. Mol. Neurobiol.

    (1985)
  • N. Toni

    LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite

    Nature

    (1999)
  • R. Yuste et al.

    Morphological changes in dendritic spines associated with long-term synaptic plasticity

    Annu. Rev. Neurosci.

    (2001)
  • H. Hering et al.

    Dendritic spines: structure, dynamics and regulation

    Nat. Rev. Neurosci.

    (2001)
  • Z. Parnass

    Analysis of spine morphological plasticity in developing hippocampal pyramidal neurons

    Hippocampus

    (2000)
  • J.T. Trachtenberg

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

    Nature

    (2002)
  • J. Grutzendler

    Long-term dendritic spine stability in the adult cortex

    Nature

    (2002)
  • M. Maletic-Savatic

    Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity

    Science

    (1999)
  • F. Engert et al.

    Dendritic spine changes associated with hippocampal long-term synaptic plasticity

    Nature

    (1999)
  • E. Korkotian et al.

    Regulation of dendritic spine motility in cultured hippocampal neurons

    J. Neurosci.

    (2001)
  • Y. Takumi

    Different modes of expression of AMPA and NMDA receptors in hippocampal synapses

    Nat. Neurosci.

    (1999)
  • V.N. Kharazia et al.

    Immunogold localization of AMPA and NMDA receptors in somatic sensory cortex of albino rat

    J. Comp. Neurol.

    (1999)
  • K.M. Harris et al.

    Dendritic spines of CA1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics

    J. Neurosci.

    (1989)
  • M. Matsuzaki

    Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

    Nat. Neurosci.

    (2001)
  • J. Morrison

    Mechanisms of photorelease of carboxylic acids from 1-acyl-7-nitroindolines in solutions of varying water content

    Photochem. Photobiol. Sci.

    (2002)
  • M. Smith

    Mechanism of the distance-dependent scaling of Schaffer collateral synapse in CA1 pyramidal neurons

    J. Physiol.

    (2003)
  • Cited by (709)

    View all citing articles on Scopus
    View full text