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<p>Synaptic plasticity alters neuronal connections in response to experience, which is thought to underlie learning and memory. However, the loci of learning-related synaptic plasticity, and the degree to which plasticity is localized or distributed, remain largely unknown. Here we describe a new method, DELTA, for mapping brain-wide changes in synaptic protein turnover with single-synapse resolution, based on Janelia Fluor dyes and HaloTag knock-in mice. During associative learning, the turnover of the ionotropic glutamate receptor subunit GluA2, an indicator of synaptic plasticity, was enhanced in several brain regions, most markedly hippocampal area CA1. More broadly distributed increases in the turnover of synaptic proteins were observed in response to environmental enrichment. In CA1, GluA2 stability was regulated in an input-specific manner, with more turnover in layers containing input from CA3 compared to entorhinal cortex. DELTA will facilitate exploration of the molecular and circuit basis of learning and memory and other forms of plasticity at scales ranging from single synapses to the entire brain.</p>

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DELTA: a method for brain-wide measurement of synaptic protein turnover reveals localized plasticity during learning

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月31日

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  • Boaz Mohar,
  • Gabriela Michel,
  • Yi-Zhi Wang,
  • Veronica Hernandez,
  • Jonathan B. Grimm,
  • Jin-Yong Park,
  • Ronak Patel,
  • Morgan Clarke,
  • Timothy A. Brown,
  • Cornelius Bergmann,
  • Kamil K. Gebis,
  • Anika P. Wilen,
  • Bian Liu,
  • Richard Johnson,
  • Austin Graves,
  • Tatjana Tchumatchenko,
  • Jeffrey N. Savas,
  • Eugenio F. Fornasiero,
  • Richard L. Huganir,
  • Paul W. Tillberg,
  • Luke D. Lavis,
  • Karel Svoboda,
  • Nelson Spruston

摘要

Synaptic plasticity alters neuronal connections in response to experience, which is thought to underlie learning and memory. However, the loci of learning-related synaptic plasticity, and the degree to which plasticity is localized or distributed, remain largely unknown. Here we describe a new method, DELTA, for mapping brain-wide changes in synaptic protein turnover with single-synapse resolution, based on Janelia Fluor dyes and HaloTag knock-in mice. During associative learning, the turnover of the ionotropic glutamate receptor subunit GluA2, an indicator of synaptic plasticity, was enhanced in several brain regions, most markedly hippocampal area CA1. More broadly distributed increases in the turnover of synaptic proteins were observed in response to environmental enrichment. In CA1, GluA2 stability was regulated in an input-specific manner, with more turnover in layers containing input from CA3 compared to entorhinal cortex. DELTA will facilitate exploration of the molecular and circuit basis of learning and memory and other forms of plasticity at scales ranging from single synapses to the entire brain.