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Dendritic spines and long-term plasticity

Key Points

  • Despite extensive interest in dendritic spines, little is known about their assumed role in memory storage — in fact, even the type of morphological change that a spine undergoes during a change in synaptic efficacy is not yet clear.

  • The use of modern time-lapse imaging methods in both in vitro and in vivo preparations has already yielded interesting observations about spine stability, and these methods promise rapid progress in this field in the near future.

  • So far, two main types of change have been observed in dendritic spines following the induction of long-term potentiation, or the application of patterned or memory-forming stimulation. These include a rapid but transient expansion of the spine head and the slow formation of new dendritic spines.

  • Two opposite changes have also been observed, including spine shrinkage and possible pruning of spines, although the association of these changes with long-term depression or memory extinction has still not been clarified.

  • Several criteria must be met in order to claim a causative relationship between memory formation and an underlying morphological change in dendritic spines. The rapid rate at which these studies are conducted promises that the spine enigma, which has been with us for the past century, will soon be solved.

Abstract

A recent flurry of time-lapse imaging studies of live neurons have tried to address the century-old question: what morphological changes in dendritic spines can be related to long-term memory? Changes that have been proposed to relate to memory include the formation of new spines, the enlargement of spine heads and the pruning of spines. These observations also relate to a more general question of how stable dendritic spines are. The objective of this review is to critically assess the new data and to propose much needed criteria that relate spines to memory, thereby allowing progress in understanding the morphological basis of memory.

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Figure 1: Three-dimensional reconstructed electron microscopy picture of a dendrite, two spines and an associated axon.
Figure 2: Changes in dendritic spines in cultured hippocampal neurons after conditioning stimulation.
Figure 3: Schematic illustration of possible sequential changes in dendritic spines at various stages of long-term memory formation.

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Acknowledgements

I would like to thank K. Braun for the use of the EM picture, E. Korkotian for help with the figures and M. Brodt for comments on the manuscript. Supported by a grant from the Israel Science Foundation.

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DATABASES

Entrez Gene

CaMKII

mGluR1

PAK3

PSD-95

FURTHER INFORMATION

Segal's laboratory

Glossary

ENRICHED ENVIRONMENT

Growing a young mammal in an environment that is enriched with stimuli and motor demands has been shown to enhance the cognitive skills of that animal, as well as the complexity of its neurons.

TWO-PHOTON MICROSCOPY

A form of microscopy in which a fluorochrome that would normally be excited by a single photon is stimulated quasi-simultaneously by two photons of lower energy. Under these conditions, fluorescence increases as a function of the square of the light intensity, and decreases as the fourth power of the distance from the focus. Because of this behaviour, only fluorochrome molecules near the plane of focus are excited, greatly reducing light scattering and photodamage of the sample.

FILOPODIUM

A highly motile cytoplasmic extension of an axon or dendrite that is 2–10 μm long and less than 1 μm thick. It is assumed to serve as a sensing element in the formation of synaptic contacts with adjacent neurons.

MINIATURE EXCITATORY POSTSYNAPTIC CURRENT

(mEPSC). When action potential activity is blocked, recording can be made of currents that are produced by the release of neurotransmitter at a single synapse.

LONG-TERM POTENTIATION

(LTP). A long lasting (hours or days) increase in the response of neurons to stimulation of their afferents following a brief patterned stimulus (for example, a 100-Hz stimulus).

LONG-TERM DEPRESSION

(LTD). A long lasting decrease in the response of neurons to stimulation of their afferents following a brief patterned stimulus (for example, a 1-Hz stimulus).

HOMEOSTATIC PLASTICITY

When synaptic activity is reduced by the blockade of spike activity, the affected neuron responds by increasing the efficacy of individual synaptic currents, and vice versa: when activity is enhanced, the neuron downregulates the size of its synaptic currents.

FLUORESCENCE RESONANCE ENERGY TRANSFER

(FRET). A spectroscopic technique that is based on the transfer of energy from the excited state of a donor moiety to an acceptor. The transfer efficiency depends on the distance between the donor and the acceptor. FRET is often used to estimate distances between macromolecular sites in the 20–100-Å range, or to study interactions between macromolecules in vivo.

IMPRINTING

The long-lasting change in the behaviour of a young chick following exposure to a moving object that mimics a parent.

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Segal, M. Dendritic spines and long-term plasticity. Nat Rev Neurosci 6, 277–284 (2005). https://doi.org/10.1038/nrn1649

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