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A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge.

Melissa R Warden1, Aslihan Selimbeyoglu, Julie J Mirzabekov

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Specific medial prefrontal cortex (mPFC) cells projecting to the dorsal raphe nucleus (DRN) causally control active behavioral responses. Activating these mPFC-DRN pathways rapidly influences action selection in challenging situations.

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Area of Science:

  • Neuroscience
  • Behavioral Neuroscience
  • Computational Neuroscience

Background:

  • The prefrontal cortex (PFC) plays a crucial role in behavioral control, with dysfunction linked to impulsivity or amotivation.
  • Understanding the specific neural circuitry within the PFC that drives effortful action is essential for addressing behavioral disorders.

Purpose of the Study:

  • To investigate the medial prefrontal cortex (mPFC) circuitry underlying the selection of active behavioral responses to challenges.
  • To identify specific neuronal populations within the mPFC that causally influence action selection and motivation.

Main Methods:

  • Developed a quantitative method for continuous assessment of active behavioral responses in freely moving rats.
  • Utilized single-unit electrophysiology and optogenetics for real-time monitoring and manipulation of neural activity.
  • Employed projection-targeting optogenetics to selectively activate mPFC neurons with specific downstream connections.

Main Results:

  • Many mPFC neurons showed moment-to-moment modulation of firing patterns related to the decision to act.
  • Direct activation of general mPFC principal neurons did not affect active behavior.
  • Selective activation of mPFC cells projecting to the dorsal raphe nucleus (DRN) profoundly and reversibly altered active behavioral state selection.

Conclusions:

  • Specific mPFC subpopulations, defined by their projections to the DRN, are critical for driving active behavioral responses.
  • These findings shed light on the neural mechanisms of action selection and motivation.
  • The results offer insights into the neural circuitry underlying normal and pathological motivation, potentially relevant to conditions like depression.