{
  "abstract": "Labile zinc ions (Zn²⁺) are stored in glutamatergic vesicles at specific excitatory synapses in the central nervous system and released into synaptic clefts in an activity-dependent manner. However, the precise roles of synaptic Zn²⁺ remain unclear due to a lack of tools capable of analyzing Zn²⁺ with synapse-level spatial resolution in vivo. Here, we developed neuroreceptor-based semisynthetic biosensors that function as integrating dosimeters, recording synaptic Zn²⁺ by covalent chemistry in the living mouse brain. Using a chemical knock-in strategy, we introduced activity-based Zn²⁺ probes with distinct affinities into endogenous α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid or γ-aminobutyric acid type A receptors. These in-brain-constructed Zn²⁺ sensors enabled region-specific mapping of Zn²⁺ in synaptic clefts in the living mouse brain. Imaging-based analyses revealed differences in apparent Zn²⁺ levels at excitatory and inhibitory synapses across hippocampal regions during kainate-induced seizures, providing insights into the physiological and pathological functions of synaptic Zn²⁺.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.",
    "Division of Synthetic Chemistry for Molecular Systems, SANKEN (The Institute of Scientific and Industrial Research), The University of Osaka, Ibaraki 567-0047, Japan.",
    "Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.",
    "Biomolecular Organization Chemistry Research Section, Institute of Advanced Energy, Kyoto University, Uji 611-0011, Japan."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Hao Zhu",
      "orcid": "0000-0003-3640-2290"
    },
    {
      "affs": [
        0
      ],
      "name": "Seiji Sakamotob",
      "orcid": "0000-0002-0605-0987"
    },
    {
      "affs": [
        0
      ],
      "name": "Keisuke Nakamura"
    },
    {
      "affs": [
        0
      ],
      "name": "Chengli Qiu"
    },
    {
      "affs": [
        0
      ],
      "name": "Kohei Nakajima"
    },
    {
      "affs": [
        2
      ],
      "name": "Hiroshi Nonaka"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Itaru Hamachi",
      "orcid": "0000-0002-3327-3916"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ape2r3w14b2f0.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2606947123",
  "fulltext_url": "https://europepmc.org/articles/PMC13684168",
  "id": "ape2r3w14b2f0",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://europepmc.org/article/MED/42863051",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2804|Neuroscience and Neuropharmacology Research"
    ]
  ],
  "openalex": "W7221566551",
  "pdf_url": "https://europepmc.org/articles/PMC13684168?pdf=render",
  "pmcid": "PMC13684168",
  "pmid": "42863051",
  "published": "2026-10-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ape2r3w14b2f0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42863051",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42863051"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Neuroscience and Neuropharmacology Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "Imaging and recording of synaptic zinc in the brain by covalent chemistry-based semisynthetic biosensors.",
  "title_text": "Imaging and recording of synaptic zinc in the brain by covalent chemistry-based semisynthetic biosensors.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/ape2r3w14b2f0",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}