Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Molecular genetics and imaging technologies for circuit-based neuroanatomy

Nature volume 461, pages 900–907 (2009)Cite this article

Abstract

Brain function emerges from the morphologies, spatial organization and patterns of connectivity established between diverse sets of neurons. Historically, the notion that neuronal structure predicts function stemmed from classic histological staining and neuronal tracing methods. Recent advances in molecular genetics and imaging technologies have begun to reveal previously unattainable details about patterns of functional circuit connectivity and the subcellular organization of synapses in the living brain. This sophisticated molecular and genetic 'toolbox', coupled with new methods in optical and electron microscopy, provides an expanding array of techniques for probing neural anatomy and function.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Viral vectors for trans-synaptic labelling.
Figure 2: Conditional anatomy using the Brainbow system.

References

  1. Helmstaedter, M., Briggman, K. L. & Denk, W. 3D structural imaging of the brain with photons and electrons. Curr. Opin. Neurobiol. 18, 633–641 (2008).

    Article  CAS  PubMed  Google Scholar 

  2. Palay, S. L. & Palade, G. E. The fine structure of neurons. J. Biophys. Biochem. Cytol. 1, 69–88 (1955).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Macagno, E. R., Levinthal, C. & Sobel, I. Three-dimensional computer reconstruction of neurons and neuronal assemblies. Annu. Rev. Biophys. Bioeng. 8, 323–351 (1979).

    Article  CAS  PubMed  Google Scholar 

  4. White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. The structure of the nervous system of the nematode Caenorhabditis elegans. Phil. Trans. R. Soc. Lond. B 314, 1–340 (1986).

    Article  ADS  CAS  Google Scholar 

  5. Ahmed, B., Anderson, J. C., Martin, K. A. & Nelson, J. C. Map of the synapses onto layer 4 basket cells of the primary visual cortex of the cat. J. Comp. Neurol. 380, 230–242 (1997).

    Article  CAS  PubMed  Google Scholar 

  6. Anderson, J. C., Douglas, R. J., Martin, K. A. & Nelson, J. C. Map of the synapses formed with the dendrites of spiny stellate neurons of cat visual cortex. J. Comp. Neurol. 341, 25–38 (1994).

    Article  CAS  PubMed  Google Scholar 

  7. Stevens, J. K., McGuire, B. A. & Sterling, P. Toward a functional architecture of the retina: serial reconstruction of adjacent ganglion cells. Science 207, 317–319 (1980).

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Briggman, K. L. & Denk, W. Towards neural circuit reconstruction with volume electron microscopy techniques. Curr. Opin. Neurobiol. 16, 562–570 (2006).

    Article  CAS  PubMed  Google Scholar 

  9. Micheva, K. D. & Smith, S. J. Array tomography: a new tool for imaging the molecular architecture and ultrastructure of neural circuits. Neuron 55, 25–36 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Harris, K. M. et al. Uniform serial sectioning for transmission electron microscopy. J. Neurosci. 26, 12101–12103 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Knott, G., Marchman, H., Wall, D. & Lich, B. Serial section scanning electron microscopy of adult brain tissue using focused ion beam milling. J. Neurosci. 28, 2959–2964 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Luo, L., Callaway, E. M. & Svoboda, K. Genetic dissection of neural circuits. Neuron 57, 634–660 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Giepmans, B. N., Adams, S. R., Ellisman, M. H. & Tsien, R. Y. The fluorescent toolbox for assessing protein location and function. Science 312, 217–224 (2006).

    Article  ADS  CAS  PubMed  Google Scholar 

  14. Feng, G. et al. Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51 (2000).

    Article  CAS  PubMed  Google Scholar 

  15. Heiman, M. et al. A translational profiling approach for the molecular characterization of CNS cell types. Cell 135, 738–748 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kerr, J. N. & Denk, W. Imaging in vivo: watching the brain in action. Nature Rev. Neurosci. 9, 195–205 (2008).

    Article  CAS  Google Scholar 

  17. Svoboda, K. & Yasuda, R. Principles of two-photon excitation microscopy and its applications to neuroscience. Neuron 50, 823–839 (2006).

    Article  CAS  PubMed  Google Scholar 

  18. Hell, S. W. Microscopy and its focal switch. Nature Methods 6, 24–32 (2009).

    Article  CAS  PubMed  Google Scholar 

  19. Capecchi, M. R. Altering the genome by homologous recombination. Science 244, 1288–1292 (1989).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Young, P. et al. Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice. Nature Neurosci. 11, 721–728 (2008).

    Article  ADS  CAS  PubMed  Google Scholar 

  21. Zong, H., Espinosa, J. S., Su, H. H., Muzumdar, M. D. & Luo, L. Mosaic analysis with double markers in mice. Cell 121, 479–492 (2005).

    Article  CAS  PubMed  Google Scholar 

  22. Branda, C. S. & Dymecki, S. M. Talking about a revolution: the impact of site-specific recombinases on genetic analyses in mice. Dev. Cell 6, 7–28 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Tsien, J. Z. et al. Subregion- and cell type-restricted gene knockout in mouse brain. Cell 87, 1317–1326 (1996). This was the first primary research paper describing the use of the Cre/ loxP recombination system for conditional mutagenesis in the mouse nervous system.

    Article  CAS  PubMed  Google Scholar 

  24. Lein, E. S. et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 445, 168–176 (2007). This paper describes the development and function of the publicly accessible digital atlas of in situ gene expression patterns created by the Allen Institute for Brain Science for all annotated genes in the rodent brain.

    Article  ADS  CAS  PubMed  Google Scholar 

  25. Boldogkoi, Z. et al. Genetically timed, activity-sensor and rainbow transsynaptic viral tools. Nature Methods 6, 127–130 (2009).

    Article  CAS  PubMed  Google Scholar 

  26. Wickersham, I. R., Finke, S., Conzelmann, K. K. & Callaway, E. M. Retrograde neuronal tracing with a deletion-mutant rabies virus. Nature Methods 4, 47–49 (2007).

    Article  CAS  PubMed  Google Scholar 

  27. Wickersham, I. R. et al. Monosynaptic restriction of transsynaptic tracing from single, genetically targeted neurons. Neuron 53, 639–647 (2007). This paper describes a creative approach to genetically targeting neuronal subsets for rabies virus infection and circuit tracing while also restricting viral propagation to single presynaptic targets by viral capsid complementation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Arenkiel, B. R., Klein, M. E., Davison, I. G., Katz, L. C. & Ehlers, M. D. Genetic control of neuronal activity in mice conditionally expressing TRPV1. Nature Methods 5, 299–302 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Boyden, E. S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neurosci. 8, 1263–1268 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Zhang, F. et al. Multimodal fast optical interrogation of neural circuitry. Nature 446, 633–639 (2007).

    Article  ADS  CAS  PubMed  Google Scholar 

  31. Lerchner, W. et al. Reversible silencing of neuronal excitability in behaving mice by a genetically targeted, ivermectin-gated Cl− channel. Neuron 54, 35–49 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Tan, E. M. et al. Selective and quickly reversible inactivation of mammalian neurons in vivo using the Drosophila allatostatin receptor. Neuron 51, 157–170 (2006).

    Article  CAS  PubMed  Google Scholar 

  33. Callaway, E. M. Transneuronal circuit tracing with neurotropic viruses. Curr. Opin. Neurobiol. 18, 617–623 (2008).

    Article  CAS  PubMed  Google Scholar 

  34. Zhao, G. Q. et al. The receptors for mammalian sweet and umami taste. Cell 115, 255–266 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Drenan, R. M. et al. In vivo activation of midbrain dopamine neurons via sensitized, high-affinity α6* nicotinic acetylcholine receptors. Neuron 60, 123–136 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Conklin, B. R. et al. Engineering GPCR signaling pathways with RASSLs. Nature Methods 5, 673–678 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wulff, P. et al. From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Nature Neurosci. 10, 923–929 (2007).

    Article  CAS  PubMed  Google Scholar 

  38. Ehlers, M. D., Heine, M., Groc, L., Lee, M. C. & Choquet, D. Diffusional trapping of GluR1 AMPA receptors by input-specific synaptic activity. Neuron 54, 447–460 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Karpova, A. Y., Tervo, D. G., Gray, N. W. & Svoboda, K. Rapid and reversible chemical inactivation of synaptic transmission in genetically targeted neurons. Neuron 48, 727–735 (2005).

    Article  CAS  PubMed  Google Scholar 

  40. Nakashiba, T., Young, J. Z., McHugh, T. J., Buhl, D. L. & Tonegawa, S. Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning. Science 319, 1260–1264 (2008).

    Article  ADS  CAS  PubMed  Google Scholar 

  41. Sjostrom, P. J., Rancz, E. A., Roth, A. & Hausser, M. Dendritic excitability and synaptic plasticity. Physiol. Rev. 88, 769–840 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. Groc, L. et al. Surface trafficking of neurotransmitter receptor: comparison between single-molecule/quantum dot strategies. J. Neurosci. 27, 12433–12437 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Newpher, T. M. & Ehlers, M. D. Glutamate receptor dynamics in dendritic microdomains. Neuron 58, 472–497 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Fernandez-Alfonso, T., Kwan, R. & Ryan, T. A. Synaptic vesicles interchange their membrane proteins with a large surface reservoir during recycling. Neuron 51, 179–186 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Miesenbock, G., De Angelis, D. A. & Rothman, J. E. Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature 394, 192–195 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  46. Zhu, Y., Xu, J. & Heinemann, S. F. Two pathways of synaptic vesicle retrieval revealed by single-vesicle imaging. Neuron 61, 397–411 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Ashby, M. C., Maier, S. R., Nishimune, A. & Henley, J. M. Lateral diffusion drives constitutive exchange of AMPA receptors at dendritic spines and is regulated by spine morphology. J. Neurosci. 26, 7046–7055 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Blanpied, T. A., Kerr, J. M. & Ehlers, M. D. Structural plasticity with preserved topology in the postsynaptic protein network. Proc. Natl Acad. Sci. USA 105, 12587–12592 (2008).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  49. Bozza, T., McGann, J. P., Mombaerts, P. & Wachowiak, M. In vivo imaging of neuronal activity by targeted expression of a genetically encoded probe in the mouse. Neuron 42, 9–21 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Park, M. et al. Plasticity-induced growth of dendritic spines by exocytic trafficking from recycling endosomes. Neuron 52, 817–830 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yudowski, G. A. et al. Real-time imaging of discrete exocytic events mediating surface delivery of AMPA receptors. J. Neurosci. 27, 11112–11121 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Feinberg, E. H. et al. GFP reconstitution across synaptic partners (GRASP) defines cell contacts and synapses in living nervous systems. Neuron 57, 353–363 (2008).

    Article  CAS  PubMed  Google Scholar 

  53. Harvey, C. D., Yasuda, R., Zhong, H. & Svoboda, K. The spread of Ras activity triggered by activation of a single dendritic spine. Science 321, 136–140 (2008).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lee, S. J., Escobedo-Lozoya, Y., Szatmari, E. M. & Yasuda, R. Activation of CaMKII in single dendritic spines during long-term potentiation. Nature 458, 299–304 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  55. Triller, A. & Choquet, D. New concepts in synaptic biology derived from single-molecule imaging. Neuron 59, 359–374 (2008).

    Article  CAS  PubMed  Google Scholar 

  56. Zhang, Q., Cao, Y. Q. & Tsien, R. W. Quantum dots provide an optical signal specific to full collapse fusion of synaptic vesicles. Proc. Natl Acad. Sci. USA 104, 17843–17848 (2007).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhang, Q., Li, Y. & Tsien, R. W. The dynamic control of kiss-and-run and vesicular reuse probed with single nanoparticles. Science 323, 1448–1453 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  58. Howarth, M. et al. Monovalent, reduced-size quantum dots for imaging receptors on living cells. Nature Methods 5, 397–399 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Gray, N. W., Weimer, R. M., Bureau, I. & Svoboda, K. Rapid redistribution of synaptic PSD-95 in the neocortex in vivo. PLoS Biol. 4, e370 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Mizrahi, A. Dendritic development and plasticity of adult-born neurons in the mouse olfactory bulb. Nature Neurosci. 10, 444–452 (2007).

    Article  CAS  PubMed  Google Scholar 

  61. Nagerl, U. V., Kostinger, G., Anderson, J. C., Martin, K. A. & Bonhoeffer, T. Protracted synaptogenesis after activity-dependent spinogenesis in hippocampal neurons. J. Neurosci. 27, 8149–8156 (2007).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  62. Huang, B., Bates, M. & Zhuang, X. Super-resolution fluorescence microscopy. Annu. Rev. Biochem. 78, 993–1016 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lippincott-Schwartz, J. & Manley, S. Putting super-resolution fluorescence microscopy to work. Nature Methods 6, 21–23 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Nagerl, U. V., Willig, K. I., Hein, B., Hell, S. W. & Bonhoeffer, T. Live-cell imaging of dendritic spines by STED microscopy. Proc. Natl Acad. Sci. USA 105, 18982–18987 (2008). This paper describes the first study implementing stimulated-emission depletion techniques to image morphological plasticity of dendritic spines non-invasively at subdiffraction resolution.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  65. Gustafsson, M. G., Agard, D. A. & Sedat, J. W. I5M: 3D widefield light microscopy with better than 100 nm axial resolution. J. Microsc. 195, 10–16 (1999).

    Article  CAS  PubMed  Google Scholar 

  66. Hell, S. W. & Stelzer, E. H. K. Fundamental improvement of resolution with a 4Pi-confocal fluorescence microscope using two-photon excitation. Opt. Commun. 93, 277–282 (1992). This paper reports the first significant increase in axial resolution of fluorescent confocal imaging by coherent use of opposing lenses.

    Article  ADS  Google Scholar 

  67. Bailey, B., Farkas, D. L., Taylor, D. L. & Lanni, F. Enhancement of axial resolution in fluorescence microscopy by standing-wave excitation. Nature 366, 44–48 (1993).

    Article  ADS  CAS  PubMed  Google Scholar 

  68. Kner, P., Chhun, B. B., Griffis, E. R., Winoto, L. & Gustafsson, M. G. Super-resolution video microscopy of live cells by structured illumination. Nature Methods 6, 339–342 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Klar, T. A., Jakobs, S., Dyba, M., Egner, A. & Hell, S. W. Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission. Proc. Natl Acad. Sci. USA 97, 8206–8210 (2000). This paper reports the first study describing the bettering of diffraction-limited resolution by stimulated-emission depletion, a technique that relies on quenching excited organic molecules at the edge of focal spot being stimulated.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  70. Betzig, E. et al. Imaging intracellular fluorescent proteins at nanometer resolution. Science 313, 1642–1645 (2006). This paper describes the first use of super-resolution imaging in photoactivated localization microscopy of fixed cells, a technique that allows super-resolution by stochastic fluorophore switching and counter-bleaching to detect the positions of individual fluorescent molecules.

    Article  ADS  CAS  PubMed  Google Scholar 

  71. Hess, S. T., Girirajan, T. P. & Mason, M. D. Ultra-high resolution imaging by fluorescence photoactivation localization microscopy. Biophys. J. 91, 4258–4272 (2006).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  72. Rust, M. J., Bates, M. & Zhuang, X. Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nature Methods 3, 793–795 (2006). This paper describes stochastic optical resolution microscopy, a super-resolution imaging technique that allows the localization of individual fluorescent molecules at nanometre resolution by switching the fluorescent tags on and off using light of different colours and variable energies.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Sakmann, B. & Neher, E. Patch clamp techniques for studying ionic channels in excitable membranes. Annu. Rev. Physiol. 46, 455–472 (1984).

    Article  CAS  PubMed  Google Scholar 

  74. Lichtman, J. W. & Sanes, J. R. Ome sweet ome: what can the genome tell us about the connectome? Curr. Opin. Neurobiol. 18, 346–353 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Seung, H. S. Reading the book of memory: sparse sampling versus dense mapping of connectomes. Neuron 62, 17–29 (2009).

    Article  CAS  PubMed  Google Scholar 

  76. Livet, J. et al. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 450, 56–62 (2007). This paper describes a creative genetic approach to stochastically label neuronal subsets in the living mouse brain with different colours using Cre-mediated recombination to drive fluorescent-reporter expression.

    Article  ADS  CAS  PubMed  Google Scholar 

  77. Arenkiel, B. R. et al. In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2. Neuron 54, 205–218 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Gradinaru, V., Mogri, M., Thompson, K. R., Henderson, J. M. & Deisseroth, K. Optical deconstruction of Parkinsonian neural circuitry. Science 324, 354–359 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  79. Petreanu, L., Huber, D., Sobczyk, A. & Svoboda, K. Channelrhodopsin-2-assisted circuit mapping of long-range callosal projections. Nature Neurosci. 10, 663–668 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. Petreanu, L., Mao, T., Sternson, S. M. & Svoboda, K. The subcellular organization of neocortical excitatory connections. Nature 457, 1142–1145 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lichtman, J. W., Livet, J. & Sanes, J. R. A technicolour approach to the connectome. Nature Rev. Neurosci. 9, 417–422 (2008).

    Article  CAS  Google Scholar 

  82. Bourne, J. N. & Harris, K. M. Balancing structure and function at hippocampal dendritic spines. Annu. Rev. Neurosci. 31, 47–67 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Denk, W. & Horstmann, H. Serial block-face scanning electron microscopy to reconstruct three-dimensional tissue nanostructure. PLoS Biol. 2, e329 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Soto, G. E. et al. Serial section electron tomography: a method for three-dimensional reconstruction of large structures. Neuroimage 1, 230–243 (1994).

    Article  CAS  PubMed  Google Scholar 

  85. Harlow, M. L., Ress, D., Stoschek, A., Marshall, R. M. & McMahan, U. J. The architecture of active zone material at the frog's neuromuscular junction. Nature 409, 479–484 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  86. Macke, J. H. et al. Contour-propagation algorithms for semi-automated reconstruction of neural processes. J. Neurosci. Methods 167, 349–357 (2008).

    Article  PubMed  Google Scholar 

  87. Hell, S. W. & Kroug, M. Ground-state-depletion fluorescence microscopy: a concept for breaking the diffraction resolution limit. Appl. Phys. B 60, 495–497 (1995).

    Article  ADS  Google Scholar 

  88. Gustafsson, M. G. Nonlinear structured-illumination microscopy: wide-field fluorescence imaging with theoretically unlimited resolution. Proc. Natl Acad. Sci. USA 102, 13081–13086 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  89. Thompson, R. E., Larson, D. R. & Webb, W. W. Precise nanometer localization analysis for individual fluorescent probes. Biophys. J. 82, 2775–2783 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Folling, J. et al. Fluorescence nanoscopy by ground-state depletion and single-molecule return. Nature Methods 5, 943–945 (2008).

    Article  PubMed  CAS  Google Scholar 

  91. Sharonov, A. & Hochstrasser, R. M. Wide-field subdiffraction imaging by accumulated binding of diffusing probes. Proc. Natl Acad. Sci. USA 103, 18911–18916 (2006).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  92. Huang, B., Wang, W., Bates, M. & Zhuang, X. Three-dimensional super-resolution imaging by stochastic optical reconstruction microscopy. Science 319, 810–813 (2008).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  93. Huang, B., Jones, S. A., Brandenburg, B. & Zhuang, X. Whole-cell 3D STORM reveals interactions between cellular structures with nanometer-scale resolution. Nature Methods 5, 1047–1052 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Shtengel, G. et al. Interferometric fluorescent super-resolution microscopy resolves 3D cellular ultrastructure. Proc. Natl Acad. Sci. USA 106, 3125–3130 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank I. Davison, D. Fitzpatrick, M. Fernandez Suarez, K. Harris, J. Hernandez, M. Kennedy, A. Mabb, R. Mooney, T. Newpher, T. Roberts, C. Robinson, J. Schwartz, R. Weinberg, X. Zhuang and J. Yi for helpful input and comments on the manuscript. We apologize to those whose work we could not cite owing to space limitations. B.R.A. is supported by a K99 award from the US National Institutes of Health (NIH). Work in the lab of M.D.E. is supported by grants from the National Institute of Neurological Disorders and Stroke, the National Institute of Mental Health and the National Institute on Aging of the NIH. M.D.E. is an Investigator of the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

  1. Department of Neurobiology,

    Benjamin R. Arenkiel & Michael D. Ehlers

  2. Howard Hughes Medical Institute, Duke University Medical Center, Box 3209, Durham, 27710, North Carolina, USA

    Michael D. Ehlers

Authors
  1. Benjamin R. Arenkiel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael D. Ehlers
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Reprints and permissions information is available at http://www.nature.com/reprints.

Correspondence should be addressed to M.D.E. (ehlers@neuro.duke.edu).

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Arenkiel, B., Ehlers, M. Molecular genetics and imaging technologies for circuit-based neuroanatomy. Nature 461, 900–907 (2009). https://doi.org/10.1038/nature08536

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature08536

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing