Core Viewpoint - The research highlights the development of an efficient method to differentiate human pluripotent stem cells (hPSCs) into A10 subtype midbrain dopaminergic neurons (A10 mDA), which can integrate into mouse brain circuits and improve depression-like behaviors [3][6][9]. Group 1: Research Background - A10 mDA neurons play a crucial role in reward-related and goal-directed behaviors and are considered target cells for treating various mental disorders, including depression [3][5]. - Previous studies have successfully induced differentiation of midbrain dopaminergic neurons (mDA) from hPSCs, but efficient differentiation of A10 mDA has been challenging [5][6]. Group 2: Research Methodology - The study reports a method for efficiently differentiating A10 mDA from hPSCs using Notch inhibitors, glial cell-derived neurotrophic factor (GDNF), and ascorbic acid (AA) [6][7]. - The differentiated A10 mDA neurons exhibited characteristics specific to the A10 subtype, including gene expression profiles and electrophysiological properties [6][7]. Group 3: Research Findings - Transplantation of A10 mDA into the nucleus accumbens (NAc) resulted in specific projections to endogenous target brain regions, inducing significant anti-anxiety phenotypes in normal mice and effectively alleviating depression-like phenotypes in depression model mice [6][7]. - The study emphasizes the potential of hPSC-derived neuron subtypes in treating neuropsychiatric disorders by functionally repairing damaged circuits [9].