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Related Experiment Video

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TARGETING INSULO-FRONTAL PATHWAY TO REDUCE STRESS-EVOKED COGNITIVE RIGIDITY.

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The anterior insular cortex (aIC) circuit to the medial prefrontal cortex (mPFC) regulates cognitive flexibility. This pathway

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Area of Science:

  • Neuroscience
  • Cognitive Science
  • Behavioral Neuroscience

Background:

  • The anterior insular cortex (aIC) is crucial for the salience network and cognitive flexibility.
  • Cognitive rigidity is a hallmark of stress-related disorders, yet its neural underpinnings are not fully understood.
  • The causal role of the aIC in cognitive rigidity remains unclear.

Purpose of the Study:

  • To investigate the causal role of anterior insular cortex (aIC) projections to the medial prefrontal cortex (mPFC) in cognitive flexibility.
  • To elucidate how stress impacts aIC function and cognitive flexibility.
  • To identify the aIC→mPFC circuit as a potential therapeutic target for cognitive rigidity.

Main Methods:

  • Attentional set-shifting tasks (AST) in mice.
  • Optogenetic manipulation of aIC→mPFC projections.
  • In vivo neural activity recording during cognitive tasks.
  • Stress induction paradigms.

Main Results:

  • aIC neurons projecting to the mPFC show heightened activity after incorrect trials, signaling salience.
  • Optogenetic disruption of aIC→mPFC projections impairs adaptive decision-making and AST performance.
  • Stress disrupts aIC activity's outcome-dependence and impairs set-shifting.
  • Reinforcing aIC→mPFC activity after errors rescues cognitive flexibility in stressed mice.

Conclusions:

  • The aIC→mPFC circuit is critical for linking trial outcomes to adaptive decision-making.
  • This pathway plays a key role in maintaining cognitive flexibility.
  • The aIC→mPFC circuit represents a promising therapeutic target for stress-induced cognitive rigidity.