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<p>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 mm<sup>3</sup>) 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 <a href="http://Pyr.ai">Pyr.ai</a>, an online platform for hippocampal connectomics.</p>

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Hippocampal CA3 connectomics reveals a gradient of mossy fiber inputs and selective feedforward inhibition onto pyramidal cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Zhihao Zheng,
  • Changjoo Park,
  • Eric W. Hammerschmith,
  • Ran Lu,
  • Szi-Chieh Yu,
  • Marissa Sorek,
  • Ben Silverman,
  • Chris S. Jordan,
  • Amy R. Sterling,
  • William M. Silversmith,
  • Philipp Schlegel,
  • Gregory S. X. E. Jefferis,
  • Forrest Collman,
  • H. Sebastian Seung,
  • David W. Tank

摘要

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.