Prefrontal Neurons Projecting to the Dorsomedial Striatum and Insular Cortex Support Reward Learning
Baihui Ren1,2 · Mengmeng Shao1,2 · Qingdan Kong1,2 · Xiaobo Ma1,2 · Dongping Huang1,2 · Miao He3 · Yilin Tai3 · Jiangteng Lu1,2
1 Department of Clinical Laboratory, Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Songjiang Hospital, Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China
2 Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
3 State Key Laboratory of Brain Function and Disorders and MOE Frontiers Center for Brain Science, and the Institutes of Brain Science, Fudan University, Shanghai 200032, China
Abstract
The medial prefrontal cortex (mPFC) contains projection-defined neuronal populations that route information to multiple downstream targets. However, their role in reward learning remains unclear. Here, we identified and functionally characterized a subpopulation of mPFC neurons collateralizing to the dorsomedial striatum (DMS) and the contralateral anterior insular cortex (aIC). Fiber photometry and single-cell calcium imaging revealed that mPFCDMS+aIC neurons responded robustly to reward stimuli and exhibited learning-enhanced, unconditioned stimulus (US)-evoked activity during reward conditioning, whereas conditioned stimulus (CS) responses remained stable. This enhancement reflected an increased response magnitude and a greater proportion of US-responsive neurons. Importantly, optogenetic inhibition of these neurons during the US period, but not during the CS period, impaired the acquisition of conditioned anticipatory licking. Taken together, our findings identify a finely projection-defined mPFC neuronal subpopulation that preferentially contributes to reinforcement-related updating during reward learning.
Keywords
Dual-projection neurons; Medial prefrontal cortex; Reward learning; US-evoked activity
