Parabrachial neurons orchestrate cold-induced homeostatic responses

Thermoregulation is a fundamental physiological process essential for survival^1,2, yet how the brain represents peripheral cold sensory information and coordinates diverse adaptive responses remains incompletely understood³. Here we identify cold-activated neurons in the parabrachial nucleus (hereafter, PB^Cold neurons) as primary recipients of cold sensory input in the brain, using activity-dependent genetic labelling in mice^4,5. PB^Cold neurons exhibit rapid and sustained activation across a wide range of cold stimuli, indicating persistent encoding of environmental cooling. Transient or permanent silencing of these neurons disrupts cold-induced adaptations spanning multiple domains, including autonomic (brown adipose tissue thermogenesis and tail vasoconstriction), somatic (skeletal muscle shivering), behavioural (cold avoidance), metabolic (cold-induced hyperphagia) and affective (dopamine release to rewarding cool stimuli) responses, and compromises survival under severe cold. Conversely, activating PB^Cold neurons promotes warmth-seeking behaviour and increases food intake and energy expenditure. Molecular profiling identifies Grp and Trhr as highly specific yet partially efficient markers for PB^Cold neuron subsets. Together, these findings establish PB^Cold neurons as a critical hub coordinating cold-responsive adaptations, advancing our understanding of the central mechanisms governing thermal homeostasis.