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<p>Histamine was the first canonical monoamine identified in the mammalian brain, yet arguably remains the least understood in its mechanistic contributions to human behaviour. Using a first-in-class causal probe (H<sub>3</sub>R inverse agonist pitolisant), we show how elevating histamine shapes offline and online temporal–hippocampal dynamics — sustaining episodic learning-related activity and polarising retrieval computations. Beyond this, histamine adaptively shifts neurocomputational strategy under high working memory load, while stabilising value updates during aversive reinforcement learning. These findings uncover a mechanistically grounded influence of this underexplored system on human neurocomputation, supporting its therapeutic potential in psychiatry.</p>

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Histamine shapes the neurocomputational dynamics of human learning

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月2日

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  • Michael J. Colwell,
  • Fin J. E. van Uum,
  • Philip J. Cowen,
  • Marieke A. G. Martens,
  • Michael Browning,
  • Helen C. Barron,
  • Catherine J. Harmer,
  • Susannah E. Murphy

摘要

Histamine was the first canonical monoamine identified in the mammalian brain, yet arguably remains the least understood in its mechanistic contributions to human behaviour. Using a first-in-class causal probe (H3R inverse agonist pitolisant), we show how elevating histamine shapes offline and online temporal–hippocampal dynamics — sustaining episodic learning-related activity and polarising retrieval computations. Beyond this, histamine adaptively shifts neurocomputational strategy under high working memory load, while stabilising value updates during aversive reinforcement learning. These findings uncover a mechanistically grounded influence of this underexplored system on human neurocomputation, supporting its therapeutic potential in psychiatry.