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Hippocampal CA3 connectomics reveals a gradient of mossy fiber inputs and selective feedforward inhibition onto pyramidal cells
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DOI：10.1038/s41593-026-02388-9.png)
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Abstract
En 中文
The mossy fiber (MF) connections to pyramidal cells in hippocampal CA3 are thought to participate in pattern separation, pattern completion and memory encoding, yet no large-scale neuronal wiring diagram exists for these connections. We assembled a 3D electron microscopy volume (~1 × 1 × 0.1 mm3) from mouse hippocampal CA3. By proofreading and automated segmentation, we reconstructed and classified all soma-containing neurons—including 1,815 pyramidal cells and 229 inhibitory cells—and over 55,000 MF axons. Pyramidal cells receive more numerous MF inputs along a proximodistal gradient. Some distal cells show surprisingly high convergence via relatively small terminals with fewer vesicles. Pyramidal cells share significantly more MF inputs than networks randomized by degree-preserving swap and are better approximated by networks randomized by proximity-preserving swap. We identify a feedforward inhibitory circuit motif from MFs via perisomatic interneurons that selectively target a pyramidal subtype. We demonstrated large-scale mapping across levels in the hippocampus—from circuits to cell types to vesicles. The dataset is shared through
Pyr.ai
, an online platform for hippocampal connectomics. The authors present a dense connectomic reconstruction of a 0.1 mm3 hippocampal CA3 volume and reveal spatial gradients, high convergence and cell-type-selective feedforward inhibition of inputs to pyramidal cells.
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