A medial entorhinal connectome reveals compartmentalized microcircuit architecture
- 1Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Cente
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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BibTeX
@misc{shi2026medial,
title = {{A medial entorhinal connectome reveals compartmentalized microcircuit architecture}},
author = {T. Shi and Y. Chen and H. Jin and H. Jiang and X. Chen and Z. Xiong and F. Wu and R. Zhang},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.28.762527},
url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762527v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A medial entorhinal connectome reveals compartmentalized microcircuit architecture
AU - T. Shi
AU - Y. Chen
AU - H. Jin
AU - H. Jiang
AU - X. Chen
AU - Z. Xiong
AU - F. Wu
AU - R. Zhang
PY - 2026
DA - 2026/10/28
PB - bioRxiv
DO - 10.64898/2026.10.28.762527
UR - https://www.biorxiv.org/content/10.64898/2026.10.28.762527v1
AB - 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.
ER -