<p>Developing bioelectronics capable of stably tracking brain-wide, single-cell, millisecond-resolved neural activity in the developing brain is critical for advancing neuroscience and understanding neurodevelopmental disorders. During development, the three-dimensional structure of the vertebrate brain arises from a two-dimensional neural plate<sup><CitationRef CitationID="CR1">1</CitationRef>,<CitationRef CitationID="CR2">2</CitationRef></sup>. These large morphological changes have previously posed a challenge for implantable bioelectronics to reliably track neural activity throughout brain development<sup><CitationRef AdditionalCitationIDS="CR4 CR5 CR6 CR7 CR8" CitationID="CR3">3</CitationRef>–<CitationRef CitationID="CR9">9</CitationRef></sup>. Here we introduce a tissue-level-soft, submicrometre-thick mesh microelectrode array that integrates into the embryonic neural plate by leveraging the tissue’s natural two-dimensional-to-three-dimensional reconfiguration. As organogenesis progresses, the mesh deforms, stretches and distributes throughout the brain, seamlessly integrating with neural tissue. Immunostaining, gene expression analysis and behavioural testing confirm no adverse effects on brain development or function. This embedded electrode array enables long-term, stable mapping of how single-neuron activity and population dynamics emerge and evolve during brain development. In axolotl models, it not only records neural electrical activity during regeneration but also modulates the process through electrical stimulation.</p>

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Brain implantation of soft bioelectronics via embryonic development

  • Hao Sheng,
  • Ren Liu,
  • Qiang Li,
  • Zuwan Lin,
  • Yichun He,
  • Thomas S. Blum,
  • Hao Zhao,
  • Xin Tang,
  • Wenbo Wang,
  • Lishuai Jin,
  • Zheliang Wang,
  • Emma Hsiao,
  • Paul Le Floch,
  • Hao Shen,
  • Ariel J. Lee,
  • Rachael Alice Jonas-Closs,
  • James Briggs,
  • Siyi Liu,
  • Daniel Solomon,
  • Xiao Wang,
  • Jessica L. Whited,
  • Nanshu Lu,
  • Jia Liu

摘要

Developing bioelectronics capable of stably tracking brain-wide, single-cell, millisecond-resolved neural activity in the developing brain is critical for advancing neuroscience and understanding neurodevelopmental disorders. During development, the three-dimensional structure of the vertebrate brain arises from a two-dimensional neural plate1,2. These large morphological changes have previously posed a challenge for implantable bioelectronics to reliably track neural activity throughout brain development39. Here we introduce a tissue-level-soft, submicrometre-thick mesh microelectrode array that integrates into the embryonic neural plate by leveraging the tissue’s natural two-dimensional-to-three-dimensional reconfiguration. As organogenesis progresses, the mesh deforms, stretches and distributes throughout the brain, seamlessly integrating with neural tissue. Immunostaining, gene expression analysis and behavioural testing confirm no adverse effects on brain development or function. This embedded electrode array enables long-term, stable mapping of how single-neuron activity and population dynamics emerge and evolve during brain development. In axolotl models, it not only records neural electrical activity during regeneration but also modulates the process through electrical stimulation.