This study combines single-cell RNA-sequencing (scRNA-seq) and multiplexed error-robust FISH (MERFISH) to create a comprehensive cell atlas of the mouse hypothalamic preoptic region. The authors profiled approximately 1 million cells, identifying around 70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations. They also defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for understanding the underlying neural circuits. The approach opens new avenues for constructing cell atlases in diverse tissues and organisms.This study combines single-cell RNA-sequencing (scRNA-seq) and multiplexed error-robust FISH (MERFISH) to create a comprehensive cell atlas of the mouse hypothalamic preoptic region. The authors profiled approximately 1 million cells, identifying around 70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations. They also defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for understanding the underlying neural circuits. The approach opens new avenues for constructing cell atlases in diverse tissues and organisms.