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Review
. 2012 Aug;13(8):699-708.
doi: 10.1038/embor.2012.102. Epub 2012 Jul 13.

Dendritic spines: from structure to in vivo function

Affiliations
Review

Dendritic spines: from structure to in vivo function

Nathalie L Rochefort et al. EMBO Rep. 2012 Aug.

Abstract

Dendritic spines arise as small protrusions from the dendritic shaft of various types of neuron and receive inputs from excitatory axons. Ever since dendritic spines were first described in the nineteenth century, questions about their function have spawned many hypotheses. In this review, we introduce understanding of the structural and biochemical properties of dendritic spines with emphasis on components studied with imaging methods. We then explore advances in in vivo imaging methods that are allowing spine activity to be studied in living tissue, from super-resolution techniques to calcium imaging. Finally, we review studies on spine structure and function in vivo. These new results shed light on the development, integration properties and plasticity of spines.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Structural and molecular organization of spines. (A) Schematic drawings of spine morphologies based on the most common four-category classification. Note that on the same dendrite a continuum of shapes can be observed, and that the morphology of a spine can change rapidly. (B) Receptors and molecules related to calcium (Ca2+) signalling in spines. Red arrows indicate flux of calcium ions. AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; CaMKII, Ca2+/calmodulin-dependent kinase II; ER, endoplasmic reticulum; GAP, GTPase-activating protein; GRIP, glutamate-receptor-interacting protein; IP3(R), inositol trisphosphate (receptor); mGluR, metabotropic glutamate receptor; NMDA, N-methyl-D-aspartate; NSF, N-ethylmaleimide sensitive factor; PICK1, protein interacting with C kinase; PMCA, plasma membrane Ca2+-ATPase; PSD, postsynaptic density; RyR, ryanodine receptor; SAP97, synapse-associated protein 97; SERCA, sarco/endoplasmic reticulum Ca2+-ATPase; VGCC, voltage-gated calcium channel.
Figure 2
Figure 2
Examples of spine imaging methods in vivo. (A) In vivo chronic two-photon imaging of spine dynamics in apical dendrites of layer 5 neurons in the mouse motor cortex. Repeated imaging of the same dendritic branch revealed two neighbouring new spines (arrowheads) formed between days 1 and 4 of motor-learning task training. Scale bar, 1 μm. Neurons were labelled with YFP. Reprinted by permission from Macmillan Publishers Ltd: Nature [107] © 2012. (B) In vivo STED microscopy in the molecular layer of the somatosensory cortex of a mouse with eYFP-labelled neurons. Projected volumes of dendritic and axonal structures reveal temporal dynamics of spine morphology (lower panel). Scale bars, 1 μm. Reprinted by permission from the American Association for the Advancement of Science (AAAS) [74]. (C) In vivo two-photon spine calcium imaging using the LOTOS procedure. Left panel, two-photon image (top) and three-dimensional image reconstruction (bottom) of a dendritic segment of a layer 2/3 neuron in the mouse primary auditory cortex. Right panel, four consecutive trials of subthreshold calcium transients evoked by auditory stimulation in spines (red) and corresponding dendritic shaft regions (green), as indicated in the left panel. Reprinted by permission from [82]. LOTOS, low-power temporal oversampling; STED, stimulated emission depletion; eYFP, enhanced yellow fluorescent protein.
Figure 3
Figure 3
Imaging activity-dependent spine structural changes in vivo. (A) Spine dynamics in apical dendrites of layer 5 neurons in binocular visual cortex after monocular deprivation in adult mice. Upper panel, schemata of the mouse visual system with intrinsic signal map of the binocular visual cortex (scale bar, 500 μm) and low-magnification image of an apical dendrite (scale bar, 50 μm). Lower panel, high-magnification view of the dendritic stretch shown above (red box), imaged in vivo every four days before and after monocular deprivation (MD). Arrows point to spines appearing (red) or disappearing (blue), compared with the previous imaging session. Scale bar, 5 μm. Reprinted by permission from Macmillan Publishers Ltd: Nature [94] © 2008. (B) Spine elimination after fear conditioning in layer 5 neurons of the mouse frontal association cortex. Left panel, representative in vivo images of dendrites before and after fear conditioning with foot shock paired or unpaired with tones. Arrows and arrowheads indicate spine formation and elimination, respectively. Asterisks mark filopodia. Scale bar, 4 μm. Percentage of spine elimination and formation 48 h after conditioning. Only the paired group showed an increase in freezing response and spine elimination. Reprinted by permission from Macmillan Publishers Ltd: Nature [109] © 2012. (C) In vivo imaging of CaMKII activity in layer 2/3 neurons of the ferret visual cortex. Schematic drawing of the conformations of the FRET-based probe for the detection of CaMKII activity (Camui), in the inactive and active form. Left panel, CFP and YFP channel images of a dendritic segment as well as a ratiometric image in intensity-modulated display mode, indicating the CFP–YFP ratio. Warm hue represents high CaMKII activity. Reprinted by permission from [122], © 2011 National Academy of Sciences, USA. (D) Left panel, example of clustered synaptic SEP–GluR1 (GluR1 tagged with a pH-sensitive form of green fluorescent protein, Super Ecliptic pHluorin) enrichment in a basal dendrite of a layer 2/3 pyramidal neuron in the somatosensory cortex of a whisker-intact mouse. Scale bar, 5 μm. Right panel, profile of SEP–GluR1 spine enrichment along the dendrite shown on the left. Neighbouring spines showed a significant positive correlation value that was significantly greater than that observed in whisker-trimmed animals. Reprinted by permission from [124], © 2011, with permission from Elsevier. CaMKII, Ca2+/calmodulin-dependent kinase II; CFP, cyan fluorescent protein; FRET, Förster resonance energy transfer; GluR1, glutamate receptor 1; LGN, lateral geniculate nucleus; SEP, super ecliptic pHluorin; YFP, yellow fluorescent protein.
Figure 4
Figure 4
Imaging spine activity in vivo. (A) In vivo two-photon calcium imaging of synaptic inputs evoked by visual stimulation in a layer 2/3 pyramidal neuron of the mouse visual cortex. Red dots indicate the location of each hotspot of local dendritic calcium signal, on the Z-projection of the reconstructed dendritic tree. Red dashed lines point to the polar plot obtained for the corresponding local dendritic calcium signal. The frame (grey dashed line) indicates the area of imaging. Reprinted by permission from Macmillan Publishers Ltd: Nature [131] © 2010. (B) In vivo two-photon calcium imaging of dendritic spines of a layer 2/3 neuron in the mouse auditory cortex, using the LOTOS procedure. Frequency tuning curves of the narrowly tuned spine S1 and of the widely tuned spine S2, shown in the two-photon image in the left panel. Error bars, s.e.m. Reprinted by permission from Macmillan Publishers Ltd: Nature [82] © 2011. (C) In vivo two-photon calcium imaging of dendritic spines using conventional two-photon imaging. Left panel, a stack image of dendrites of a layer 2/3 pyramidal cell in the mouse somatosensory cortex in vivo. Right panels, typical traces of spontaneous calcium activity from eight spines detected as functionally clustered and indicated in the left panel. Reprinted by permission from the American Association for the Advancement of Science (AAAS) [127]. LOTOS, low-power temporal oversampling.

References

    1. García-López P, García-Marín V, Freire M (2007) The discovery of dendritic spines by Cajal in 1888 and its relevance in the present neuroscience. Prog Neurobiol 83: 110–130 - PubMed
    1. Shepherd GM (1996) The dendritic spine: a multifunctional integrative unit. J Neurophysiol 75: 2197–2210 - PubMed
    1. Yuste R (2011) Dendritic spines and distributed circuits. Neuron 71: 772–781 - PMC - PubMed
    1. Peters A, Kaiserman-Abramof IR (1970) The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines. Am J Anat 127: 321–355 - PubMed
    1. Jones EG, Powell TP (1969) Morphological variations in the dendritic spines of the neocortex. J Cell Sci 5: 509–529 - PubMed

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