Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• Synaptogenesis is crucial for neural circuit development.
• Its role in goal-directed voluntary behaviors remains unclear.

Purpose of the Study:

• Investigate the role of synaptogenesis in goal-directed behaviors.
• Determine the molecular mechanisms and circuit-level impact.

Main Methods:

• Operant conditioning (lever-press for food reward) in mice.
• Genetic manipulation using germline and conditional knockout mice for α2δ-1.
• Optogenetic manipulation of anterior cingulate cortex (ACC) to dorsomedial striatum (DMS) neurons.

Main Results:

• Operant conditioning induces excitatory synaptogenesis in ACC→DMS neurons.
• The α2δ-1 receptor is critical for this training-induced synaptogenesis.
• Deletion of α2δ-1 impaired synaptogenesis but did not affect learning, instead increasing effort exertion.

Conclusions:

• Synaptogenesis in the ACC→DMS circuit is vital for regulating effort, not learning itself.
• The α2δ-1 receptor plays a key role in effort-based decision-making via synaptogenesis.