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<p>Mediodorsal thalamus (MD) projections to the prefrontal cortex are crucial for adaptive cognitive functions. Using a Go/No-Go olfactory discrimination task in male mice, we investigate how MD input to the orbitofrontal cortex (OFC) regulates associative learning and modulates cue-value and outcome representations in OFC neurons. We show that inactivating MD projections to the OFC impairs learning but does not affect performance in the well-trained phase. During learning, cue value selectivity increased and outcome selectivity was dynamically reshaped in both MD and OFC, and inactivating MD projections disrupted these learning-associated changes in OFC neurons. Furthermore, MD projections targeted OFC parvalbumin (PV) interneurons, whose inactivation attenuated the learning-related enhancement of cue value selectivity and altered outcome selectivity dynamics in OFC broad-spiking cells. Thus, MD inputs engage PV interneuron-mediated feedforward inhibition to dynamically shape cue-value and outcome selectivity in the OFC, supporting associative learning.</p>

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Control of associative learning by the mediodorsal thalamus-orbitofrontal cortex circuit

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月28日

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  • Ziwei Le,
  • Can Huang,
  • Wen Zhang,
  • Dechen Liu,
  • Jingyu Ren,
  • Haishan Yao

摘要

Mediodorsal thalamus (MD) projections to the prefrontal cortex are crucial for adaptive cognitive functions. Using a Go/No-Go olfactory discrimination task in male mice, we investigate how MD input to the orbitofrontal cortex (OFC) regulates associative learning and modulates cue-value and outcome representations in OFC neurons. We show that inactivating MD projections to the OFC impairs learning but does not affect performance in the well-trained phase. During learning, cue value selectivity increased and outcome selectivity was dynamically reshaped in both MD and OFC, and inactivating MD projections disrupted these learning-associated changes in OFC neurons. Furthermore, MD projections targeted OFC parvalbumin (PV) interneurons, whose inactivation attenuated the learning-related enhancement of cue value selectivity and altered outcome selectivity dynamics in OFC broad-spiking cells. Thus, MD inputs engage PV interneuron-mediated feedforward inhibition to dynamically shape cue-value and outcome selectivity in the OFC, supporting associative learning.