Nest-building behavior in laboratory mice: Multifunctional roles and neural mechanisms

Nest-building is a multifunctional and evolutionarily conserved behavior across vertebrate species, serving critical roles in rest, thermoregulation, and offspring care. In laboratory mice, nest-building occurs spontaneously under standard housing conditions and provides an ethologically relevant window into innate behavior modulated by internal state and environmental context. Although nest-building is regarded as an innate behavior, emerging evidence demonstrates its plasticity: it is shaped by experience, hormonal state, ambient temperature, and sleep pressure. Moreover, nest-building is sensitive to strain differences, aging, stress, and neurological disorders, and may serve as a robust behavioral readout for cognitive, affective, and sensorimotor function. It may also provide a valuable indicator of general health and welfare in laboratory mice. We delineate four primary contexts for nest-building-pre-sleep, thermoregulatory, parental, and preparatory during pregnancy, and describe how distinct neural substrates involving the cerebral cortex, hypothalamus, and brain stem, are differentially engaged in each context. This review synthesizes current knowledge on the ethology, physiology, and neural circuits underlying nest-building behavior in laboratory mice.