The computational power of single neurons is greatly enhanced by active dendritic conductances1 that have a large influence on their spike activity2,3,4. In cortical output neurons such as the large pyramidal cells of layer 5 (L5), activation of apical dendritic calcium channels leads to plateau potentials that increase the gain of the input/output function5 and switch the cell to burst-firing mode6,7,8,9. The apical dendrites are innervated by local excitatory and inhibitory inputs as well as thalamic10,11,12,13 and corticocortical projections14,15,16, which makes it a formidable task to predict how these inputs influence active dendritic properties in vivo. Here we investigate activity in populations of L5 pyramidal dendrites of the somatosensory cortex in awake and anaesthetized rats following sensory stimulation using a new fibre-optic method17 for recording dendritic calcium changes. We show that the strength of sensory stimulation is encoded in the combined dendritic calcium response of a local population of L5 pyramidal cells in a graded manner. The slope of the stimulus–response function was under the control of a particular subset of inhibitory neurons activated by synaptic inputs predominantly in L5. Recordings from single apical tuft dendrites in vitro showed that activity in L5 pyramidal neurons disynaptically coupled via interneurons directly blocks the initiation of dendritic calcium spikes in neighbouring pyramidal neurons. The results constitute a functional description of a cortical microcircuit in awake animals that relies on the active properties of L5 pyramidal dendrites and their very high sensitivity to inhibition. The microcircuit is organized so that local populations of apical dendrites can adaptively encode bottom-up sensory stimuli linearly across their full dynamic range.
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London, M. & Häusser, M. Dendritic computation. Annu. Rev. Neurosci. 28, 503–532 (2005)
Llinás, R. R. The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science 242, 1654–1664 (1988)
Johnston, D., Magee, J. C., Colbert, C. M. & Christie, B. R. Active properties of neuronal dendrites. Annu. Rev. Neurosci. 19, 165–186 (1996)
Destexhe, A., Mainen, Z. F. & Sejnowski, T. J. Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism. J. Comput. Neurosci. 1, 195–230 (1994)
Larkum, M. E., Senn, W. & Lüscher, H.-R. Top-down dendritic input increases the gain of layer 5 pyramidal neurons. Cereb. Cortex 14, 1059–1070 (2004)
Schiller, J., Schiller, Y., Stuart, G. & Sakmann, B. Calcium action potentials restricted to distal apical dendrites of rat neocortical pyramidal neurons. J. Physiol. (Lond.) 505, 605–616 (1997)
Kim, H. G. & Connors, B. W. Apical dendrites of the neocortex: correlation between sodium- and calcium-dependent spiking and pyramidal cell morphology. J. Neurosci. 13, 5301–5311 (1993)
Larkum, M. E. & Zhu, J. J. Signaling of layer 1 and whisker-evoked Ca2+ and Na+ action potentials in distal and terminal dendrites of rat neocortical pyramidal neurons in vitro and in vivo . J. Neurosci. 22, 6991–7005 (2002)
Williams, S. R. & Stuart, G. J. Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons. J. Physiol. (Lond.) 521, 467–482 (1999)
White, E. L. & Hersch, S. M. A quantitative study of thalamocortical and other synapses involving the apical dendrites of corticothalamic projection cells in mouse SmI cortex. J. Neurocytol. 11, 137–157 (1982)
Hersch, S. M. & White, E. L. Thalamocortical synapses with corticothalamic projection neurons in mouse SmI cortex: electron microscopic demonstration of a monosynaptic feedback loop. Neurosci. Lett. 24, 207–210 (1981)
Zhu, Y. & Zhu, J. J. Rapid arrival and integration of ascending sensory information in layer 1 nonpyramidal neurons and tuft dendrites of layer 5 pyramidal neurons of the neocortex. J. Neurosci. 24, 1272–1279 (2004)
Oda, S. et al. Thalamocortical projection from the ventral posteromedial nucleus sends its collaterals to layer I of the primary somatosensory cortex in rat. Neurosci. Lett. 367, 394–398 (2004)
Budd, J. M. L. Extrastriate feedback to primary visual cortex in primates: a quantitative analysis of connectivity. Proc. R. Soc. Lond. B 265, 1037–1044 (1998)
Cauller, L. J. & Connors, B. W. Synaptic physiology of horizontal afferents to layer-I in slices of rat SI neocortex. J. Neurosci. 14, 751–762 (1994)
Elhanany, E. & White, E. L. Intrinsic circuitry: synapses involving the local axon collaterals of corticocortical projection neurons in the mouse primary somatosensory cortex. J. Comp. Neurol. 291, 43–54 (1990)
Murayama, M., Pérez-Garci, E., Lüscher, H. R. & Larkum, M. E. Fiberoptic system for recording dendritic calcium signals in layer 5 neocortical pyramidal cells in freely moving rats. J. Neurophysiol. 98, 1791–1805 (2007)
Kerr, J. N., Greenberg, D. & Helmchen, F. Imaging input and output of neocortical networks in vivo . Proc. Natl Acad. Sci. USA 102, 14063–14068 (2005)
Cauller, L. Layer I of primary sensory neocortex: Where top-down converges upon bottom-up. Behav. Brain Res. 71, 163–170 (1995)
Silberberg, G. & Markram, H. Disynaptic inhibition between neocortical pyramidal cells mediated by Martinotti cells. Neuron 53, 735–746 (2007)
Kapfer, C., Glickfeld, L. L., Atallah, B. V. & Scanziani, M. Supralinear increase of recurrent inhibition during sparse activity in the somatosensory cortex. Nature Neurosci. 10, 743–753 (2007)
Larkum, M. E., Kaiser, K. M. & Sakmann, B. Calcium electrogenesis in distal apical dendrites of layer 5 pyramidal cells at a critical frequency of back-propagating action potentials. Proc. Natl Acad. Sci. USA 96, 14600–14604 (1999)
Helmchen, F., Svoboda, K., Denk, W. & Tank, D. W. In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons. Nature Neurosci. 2, 989–996 (1999)
Larkum, M. E., Zhu, J. J. & Sakmann, B. A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature 398, 338–341 (1999)
Pérez-Garci, E., Gassmann, M., Bettler, B. & Larkum, M. E. The GABAB1b isoform mediates long-lasting inhibition of dendritic Ca2+ spikes in layer 5 somatosensory pyramidal neurons. Neuron 50, 603–616 (2006)
Tan, Z., Hu, H., Huang, Z. J. & Agmon, A. Robust but delayed thalamocortical activation of dendritic-targeting inhibitory interneurons. Proc. Natl Acad. Sci. USA 105, 2187–2192 (2008)
We thank K. Martin, H.-R. Lüscher and Y. Kudo for their comments on the manuscript, O. Gschwend for support in the laboratory, D. Morris for software development, D. Limoges and J. Burkhalter for their expert technical support and K. Fischer for Neurolucida reconstructions of the biocytin-filled neurons. We also thank Sumitomo Electric Industries for their generous donation of the optical fibre. This work was supported by the Swiss National Science Foundation (grant no. PP00A-102721/1).
Author Contributions M.M. and M.E.L. designed the study. M.M. performed the periscope experiments in vivo, E.P.-G. performed the in vitro experiments, and T.N. and M.M. performed the in vivo two-photon experiments. W.S. and T.B. made the model and the supplementary model description. M.M. and M.E.L. prepared the manuscript.
This file contains Supplementary Figures 1-5 with Legends and Supplementary Data with Supplementary Figures M1-M7 with Legends, Supplementary Tables 1-2 and Supplementary References (PDF 829 kb)
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Murayama, M., Pérez-Garci, E., Nevian, T. et al. Dendritic encoding of sensory stimuli controlled by deep cortical interneurons. Nature 457, 1137–1141 (2009). https://doi.org/10.1038/nature07663
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