Abstract
Transforming synaptic input into action potential output is a fundamental function of neurons. The pattern of action potential output from principal cells of the mammalian hippocampus encodes spatial and nonspatial information, but the cellular and circuit mechanisms by which neurons transform their synaptic input into a given output are unknown. Using a combination of optical activation and cell type–specific pharmacogenetic silencing in vitro, we found that dendritic inhibition is the primary regulator of input-output transformations in mouse hippocampal CA1 pyramidal cells, and acts by gating the dendritic electrogenesis driving burst spiking. Dendrite-targeting interneurons are themselves modulated by interneurons targeting pyramidal cell somata, providing a synaptic substrate for tuning pyramidal cell output through interactions in the local inhibitory network. These results provide evidence for a division of labor in cortical circuits, where distinct computational functions are implemented by subtypes of local inhibitory neurons.
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Acknowledgements
We thank R. Nyilas, R. Field, A. Qureshi, J.K. Baruni and A. Villacis for help with histology. We thank J.C. Magee, L.F. Abbott, G. Buzsáki, S.A. Siegelbaum and T.M. Jessell for discussions and comments on a previous version of the manuscript. This work was supported by Natural Sciences and Engineering Research Council of Canada Postgraduate Scholarships (M.L.-B. and P.K.), the Searle Scholar Program, the Gatsby Foundation and Kavli Institute at Columbia University (A.L.) and the Howard Hughes Medical Institute (S.M.S.). F.B. thanks the Agence Nationale pour la Recherche (France) for financial support (ANR PCV 07 10035).
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M.L.-B. and A.L. designed the study. M.L.-B., G.F.T. and A.L. performed all electrophysiological and anatomical experiments and analyzed the data. P.K. performed compartmental modeling. P.H.L. and S.M.S. provided constructs and compounds for the PSAM-PSEM method. F.B., X.-H.S. and J.F.N. synthesized and provided PENB-L-glutamate. B.V.Z. prepared plasmids, designed rAAV viruses and generated knock-in mouse lines. M.L.-B. and A.L. wrote the paper with the help of the other authors.
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Lovett-Barron, M., Turi, G., Kaifosh, P. et al. Regulation of neuronal input transformations by tunable dendritic inhibition. Nat Neurosci 15, 423–430 (2012). https://doi.org/10.1038/nn.3024
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DOI: https://doi.org/10.1038/nn.3024
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