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bioRxiv · 10.64898/2026.10.28.762527

A medial entorhinal connectome reveals compartmentalized microcircuit architecture

Shi, T.·Chen, Y.·Jin, H.·Jiang, H.·Chen, X.·Xiong, Z.·Wu, F.·Zhang, R.
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Abstract

The medial entorhinal cortex (MEC) transforms multimodal inputs into spatial representations, but the synaptic architecture underlying its computations remains unclear. Here we generated a synapse-resolution connectomic dataset spanning all six layers of mouse MEC and the adjacent parasubiculum with serial electron microscopy, providing a continuous volume for mapping cellular organization and connectivity across layers and regions. We found that clustered pyramidal neurons in MEC layer II extended oblique apical dendrites with a dorsolateral bias and long-range myelinated axons within the layer. Exhaustive reconstruction of one cluster revealed a central exclusion core (ExC) that spatially partitioned basal dendritic architecture and synaptic connectivity. A spatially constrained growth model reproduced the position-dependent dendritic patterns. Within the ExC, pyramidal neurons formed a compact recurrent excitatory network and converged onto shared inhibitory partners. Basket cells (BC) and recurrent Martinotti cells provided perisomatic and apical-dendritic feedback, respectively. Dense, compact reciprocal connectivity between L2P neurons and BCs within the ExC, together with BC axonal bands extending beyond the ExC, suggests a potential circuit mechanism for generating temporally structured inhibitory output from the pyramidal-cell cluster along directionally extended axons. Together, these findings link cellular-scale geometry and synaptic wiring to emergent circuit dynamics that extend from dense computation within individual clusters to region-wide modulation, providing a connectomic foundation for understanding the circuit basis of spatial navigation.

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Shi, T., Chen, Y., Jin, H., Jiang, H., Chen, X., Xiong, Z., Wu, F., Zhang, R.. 2026-11-03. A medial entorhinal connectome reveals compartmentalized microcircuit architecture. https://doi.org/10.64898/2026.10.28.762527

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