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Functional mapping of single spines in cortical neurons in vivo

Nature volume 475, pages 501–505 (2011)Cite this article

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Abstract

The individual functional properties and spatial arrangement of afferent synaptic inputs on dendrites have a critical role in the processing of information by neurons in the mammalian brain1,2,3,4. Although recent work has identified visually-evoked local dendritic calcium signals in the rodent visual cortex5, sensory-evoked signalling on the level of dendritic spines, corresponding to individual afferent excitatory synapses, remains unexplored6. Here we used a new variant of high-resolution two-photon imaging7 to detect sensory-evoked calcium transients in single dendritic spines of mouse cortical neurons in vivo. Calcium signals evoked by sound stimulation required the activation of NMDA (N-methyl-D-aspartate) receptors. Active spines are widely distributed on basal and apical dendrites and pure-tone stimulation at different frequencies revealed both narrowly and widely tuned spines. Notably, spines tuned for different frequencies were highly interspersed on the same dendrites: even neighbouring spines were mostly tuned to different frequencies. Thus, our results demonstrate that NMDA-receptor-dependent single-spine synaptic inputs to the same dendrite are highly heterogeneous. Furthermore, our study opens the way for in vivo mapping of functionally defined afferent sensory inputs with single-synapse resolution.

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Figure 1: Calcium signals in dendritic spines of cortical neurons in vivo.
Figure 2: Widespread dendritic distribution and sound-intensity-dependent recruitment of active spines.
Figure 3: Frequency tuning and heterogeneous distribution of individual active spines.
Figure 4: Dendritic arrangement of spines activated by the best and tail frequencies of neurons.

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Acknowledgements

We thank J. Lou for technical assistance, D. Bayer, F. Bayer and W. Zeitz for building the scanning device, A. Fohr for software support and Y. Kovalchuk and H. Adelsberger for help during the initial experiments. This work was supported by the Schiedel Foundation, the German-Israeli Foundation (GIF grant 1002/2008 to I.N. and A.K.), the Deutsche Forschungsgemeinschaft (IRTG 1373) and the Bundesministerium für Bildung und Forschung (BMBF) in the frame of ERA-NET NEURON. A.K. is a Carl-von-Linde senior fellow of the Institute for Advanced Study of the Technische Universität München.

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Author notes

  1. Xiaowei Chen and Ulrich Leischner: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, Biedersteinerstrasse 29, 80802 Munich, Germany ,

    Xiaowei Chen, Ulrich Leischner, Nathalie L. Rochefort & Arthur Konnerth

  2. Department of Neurobiology, Silberman Institute of Life Sciences and the Edmond and Lily Safra Center for Brain Sciences, Hebrew University, Jerusalem 91904, Israel,

    Israel Nelken

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  1. Xiaowei Chen
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Contributions

X.C., U.L., I.N., N.L.R. and A.K. carried out the experiments. U.L. and A.K. designed and constructed the imaging device. X.C., U.L., N.L.R., I.N. and A.K. performed the analysis. A.K. designed the study and wrote the manuscript with the help of all authors.

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Correspondence to Arthur Konnerth.

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Supplementary information

Supplementary Information

The file contains Supplementary Figures 1-11 with legends, Supplementary Table 1, the legend for Supplementary Movie 1 and additional references. (PDF 1020 kb)

Supplementary Movie 1

The movie shows three consecutive trials of spine calcium responses (S1-S4) to pure tone stimulation (0 dB attenuation; 100 ms duration) – see Supplementary Information file for full legend. (MOV 14577 kb)

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Chen, X., Leischner, U., Rochefort, N. et al. Functional mapping of single spines in cortical neurons in vivo. Nature 475, 501–505 (2011). https://doi.org/10.1038/nature10193

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