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Recurrent inhibitory circuitry as a mechanism for grid formation

Abstract

Grid cells in layer II of the medial entorhinal cortex form a principal component of the mammalian neural representation of space. The firing pattern of a single grid cell has been hypothesized to be generated through attractor dynamics in a network with a specific local connectivity including both excitatory and inhibitory connections. However, experimental evidence supporting the presence of such connectivity among grid cells in layer II is limited. Here we report recordings from more than 600 neuron pairs in rat entorhinal slices, demonstrating that stellate cells, the principal cell type in the layer II grid network, are mainly interconnected via inhibitory interneurons. Using a model attractor network, we demonstrate that stable grid firing can emerge from a simple recurrent inhibitory network. Our findings thus suggest that the observed inhibitory microcircuitry between stellate cells is sufficient to generate grid-cell firing patterns in layer II of the medial entorhinal cortex.

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Figure 1: Recurrent inhibitory connectivity in MEC layer II.
Figure 2: Stellate interconnectivity changes during early postnatal development.
Figure 3: Inhibitory connectivity between stellate cells in MEC layer II mediated by fast-spiking neurons.
Figure 4: Optical stimulation of layer II results in inhibition in stellate cells.
Figure 5: A simple inhibitory network is sufficient to generate grid cell patterns.

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Acknowledgements

We thank K. Deisseroth (Stanford University) for providing the ChR2(H134R) plasmid, I.E.J. Assebø for histological reconstructions, P. Girão for programming and A. Treves for comments on the manuscript. This work was supported by the Kavli Foundation, an EU 7th framework grant ('Spacebrain' grant agreement 200873), and Centre of Excellence (145993), equipment (181676) and research (191929) grants from the Norwegian Research Council, and an Advanced Investigator Grant from the European Research Council ('CIRCUIT', grant 232608).

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J.J.C. and M.P.W. designed the experiments. All experiments were carried out by J.J.C. with the help of R.C., who performed the stereotaxic viral injections and post-hoc immunohistochemistry, and K.Z., who helped with the cluster recordings. J.J.C., R.C. and K.Z. performed experimental analyses. A.W., B.D. and Y.R. did the network simulations. S.-J.Z. and J.Y. designed and provided the rAAV. J.J.C., A.W., Y.R., E.I.M. and M.P.W. wrote the manuscript, and all authors contributed to discussion and interpretation of results.

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Correspondence to Yasser Roudi or Menno P Witter.

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Couey, J., Witoelar, A., Zhang, SJ. et al. Recurrent inhibitory circuitry as a mechanism for grid formation. Nat Neurosci 16, 318–324 (2013). https://doi.org/10.1038/nn.3310

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