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Nature. 2017 Sep 28;549(7673):469-475. doi: 10.1038/nature24005. Epub 2017 Sep 20.

Axonal synapse sorting in medial entorhinal cortex.

Author information

Department of Connectomics, Max Planck Institute for Brain Research, D-60438 Frankfurt, Germany.
Bernstein Center for Computational Neuroscience, Humboldt University, D-10115 Berlin, Germany.
NeuroCure Cluster of Excellence, Humboldt University, D-10115 Berlin, Germany.


Research on neuronal connectivity in the cerebral cortex has focused on the existence and strength of synapses between neurons, and their location on the cell bodies and dendrites of postsynaptic neurons. The synaptic architecture of individual presynaptic axonal trees, however, remains largely unknown. Here we used dense reconstructions from three-dimensional electron microscopy in rats to study the synaptic organization of local presynaptic axons in layer 2 of the medial entorhinal cortex, the site of grid-like spatial representations. We observe path-length-dependent axonal synapse sorting, such that axons of excitatory neurons sequentially target inhibitory neurons followed by excitatory neurons. Connectivity analysis revealed a cellular feedforward inhibition circuit involving wide, myelinated inhibitory axons and dendritic synapse clustering. Simulations show that this high-precision circuit can control the propagation of synchronized activity in the medial entorhinal cortex, which is known for temporally precise discharges.

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