Prefrontal Neurons Projecting to the Dorsomedial Striatum and Insular Cortex Support Reward Learning

Area of Science:

• Neuroscience
• Behavioral Science

Background:

• The medial prefrontal cortex (mPFC) plays a role in decision-making and reward processing.
• Specific neuronal populations within the mPFC and their precise functions in reward learning are not fully understood.

Purpose of the Study:

• To identify and functionally characterize a subpopulation of mPFC neurons projecting to both the dorsomedial striatum (DMS) and anterior insular cortex (aIC).
• To investigate the role of these mPFC(DMS+aIC) neurons in reward learning and associative conditioning.

Main Methods:

• Utilized fiber photometry and single-cell calcium imaging to monitor neuronal activity.
• Employed optogenetic inhibition during conditioned (CS) and unconditioned (US) stimulus presentations in a reward conditioning paradigm.
• Assessed the impact of neuronal inhibition on the acquisition of conditioned anticipatory licking.

Main Results:

• mPFC(DMS+aIC) neurons showed robust responses to reward stimuli.
• These neurons exhibited learning-enhanced, US-evoked activity during conditioning, with increased response magnitude and proportion of responsive neurons.
• CS responses remained stable, and optogenetic inhibition during the US period, but not CS period, impaired learning.

Conclusions:

• Identified a projection-defined mPFC neuronal subpopulation (mPFC(DMS+aIC)) critical for reward learning.
• These neurons preferentially contribute to reinforcement-related neural updates during associative learning.
• Findings elucidate a specific circuit mechanism underlying reward-based behavioral modification.