Goal-directed actions and habits in head-fixed mice.

Area of Science:

• Neuroscience
• Behavioral Science
• Systems Neuroscience

Background:

• Behavioral control relies on a balance between flexible goal-directed actions and automated habits.
• An imbalance favoring habits over flexibility is linked to neuropsychiatric disorders.
• Neural circuits governing this balance are poorly understood, hindering research.

Purpose of the Study:

• Introduce and validate a novel head-fixed instrumental learning paradigm in mice.
• Enable differentiation between goal-directed and habitual behavioral control.
• Provide a platform for high-resolution, longitudinal in vivo neural interrogation.

Main Methods:

• Developed a head-fixed instrumental learning paradigm in mice.
• Used chemogenetics to inhibit the dorsolateral striatum (DLS) in limited-trained and overtrained mice.
• Assessed behavioral sensitivity to outcome devaluation and contingency reversal.

Main Results:

• Mice rapidly learned lever pressing, with overtrained mice showing insensitivity to outcome devaluation.
• Chemogenetic inhibition of the DLS in overtrained mice restored sensitivity to devaluation and contingency reversal.
• DLS inhibition blocked habit expression and preserved goal-directed control.

Conclusions:

• Established a validated paradigm for studying goal-directed actions and habits in head-fixed mice.
• Validated the dorsolateral striatum (DLS) as a key neuronal substrate for behavioral control.
• This methodological advancement facilitates longitudinal, cellular-level investigation of neural dynamics underlying behavioral flexibility.