The Medial Orbitofrontal Cortex Regulates Sensitivity to Outcome Value.

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Molecular Neuroscience

Background:

• Goal-directed decision-making relies on flexible responding to reward value.
• The medial orbitofrontal cortex (mOFC) plays a key role in regulating this process.
• Brain-derived neurotrophic factor (BDNF) is implicated in neuroplasticity and learning.

Purpose of the Study:

• To investigate the role of the mOFC and BDNF in effort-based decision-making.
• To determine if BDNF in the mOFC is necessary and sufficient for regulating responses to reward value.
• To explore the molecular mechanisms underlying BDNF's effect on goal-directed action selection.

Main Methods:

• Mice were trained on a nose-poke task for food reinforcers.
• Chemogenetic activation of mOFC neurons using DREADDs was employed.
• BDNF levels were manipulated via knockdown and replacement strategies.
• Behavioral sensitivity to reinforcer devaluation and effort allocation (progressive ratio task) were assessed.
• Molecular analyses included Western blotting for ERK1/2 phosphorylation and c-fos expression.

Main Results:

• Activation of mOFC neurons increased sensitivity to reward devaluation.
• BDNF knockdown in the mOFC impaired sensitivity to reward devaluation and altered effort allocation.
• BDNF replacement in the mOFC rescued these behavioral deficits and normalized ERK1/2 phosphorylation.
• Aberrant c-fos expression in the dorsal striatum of Bdnf(+/-) mice was normalized by mOFC BDNF replacement.
• Pharmacological inhibition of MAPK/ERK pathway and cue-based interventions affected effort allocation.

Conclusions:

• BDNF expression in the mOFC is both necessary and sufficient for regulating effort allocation based on anticipated reward value.
• The BDNF-ERK1/2 signaling pathway in the mOFC is a critical regulator of online goal-directed action selection.
• The mOFC utilizes BDNF to maintain stable representations of reinforcer value, guiding decision-making.