Nonlinear dendritic processing determines angular tuning of barrel cortex neurons in vivo

Abstract

Layer 4 neurons in primary sensory cortices receive direct sensory information from the external world1,2. A general feature of these neurons is their selectivity to specific features of the sensory stimulation3,4,5. Various theories try to explain the manner in which these neurons are driven by their incoming sensory information6,7,8,9,10,11. In all of these theories neurons are regarded as simple elements summing small biased inputs to create tuned output through the axosomatic amplification mechanism12. However, the possible role of active dendritic integration13,14,15 in further amplifying the sensory responses and sharpening the tuning curves of neurons16,17,18,19 is disregarded. Our findings show that dendrites of layer 4 spiny stellate neurons in the barrel cortex can generate local and global multi-branch N-methyl-d-aspartate (NMDA) spikes, which are the main regenerative events in these dendrites. In turn, these NMDA receptor (NMDAR) regenerative mechanisms can sum supralinearly the coactivated thalamocortical and corticocortical inputs. Using in vivo whole-cell recordings combined with an intracellular NMDAR blocker and membrane hyperpolarization, we show that dendritic NMDAR-dependent regenerative responses contribute substantially to the angular tuning of layer 4 neurons by preferentially amplifying the preferred angular directions over non-preferred angles. Taken together, these findings indicate that dendritic NMDAR regenerative amplification mechanisms contribute markedly to sensory responses and critically determine the tuning of cortical neurons.

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Figure 1: NMDA spikes in layer 4 spiny stellate neurons.
Figure 2: Corticocortical and thalamocortical pairing of activity evokes local and multi-branch global dendritic NMDA spikes.
Figure 3: The role of NMDAR-dependent dendritic regenerative responses in angular tuning of layer 4 neurons in vivo.
Figure 4: Effect of hyperpolarization on the angular tuning responses of layer 4 neurons in vivo and the effect of MK801 on angular tuning of suprathreshold responses.

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Acknowledgements

We thank Y. Schiller and G. Major for their helpful comments and discussions on the manuscript. We thank A. Korngreen and C. de Kock for help with Neurolucida reconstructions, U. Dubin for help in programming the stimulus and analysis programs, O. Schiff for help with Igor software and R. Azouz for help with the passive stimulus. We thank I. Reiter for her technical help, particularly with histology. We also thank R. Bruno for sharing his knowledge of in vivo patch clamp recordings. This study was supported by the Israel Science Foundation (ISF) and the Rappaport Foundation (J.S.).

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M.L. and L.G. performed the in vivo experiments and S.R. carried out the in vitro slice experiments and helped with analysis. A.P. performed the computer simulations. J.S. designed the study, assisted in the experiments, carried out the analysis and prepared the manuscript. M.L. also participated in the manuscript preparation.

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Correspondence to Jackie Schiller.

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The authors declare no competing financial interests.

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Lavzin, M., Rapoport, S., Polsky, A. et al. Nonlinear dendritic processing determines angular tuning of barrel cortex neurons in vivo. Nature 490, 397–401 (2012). https://doi.org/10.1038/nature11451

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