Cold is more than an uncomfortable sensation. For mammals, falling environmental temperatures trigger a coordinated emergency programme involving the brain, muscles, blood vessels, metabolism, behaviour and even the systems that shape reward. A study published in Nature Metabolism identifies a population of neurons in the parabrachial nucleus, a region of the brainstem, as a central command hub for these responses. The researchers call them PB^Cold neurons because they become active when an animal encounters cooling. Their findings suggest that the brain does not merely detect cold and respond with isolated reflexes. Instead, it routes cold sensory information through a specialized neural population capable of organizing a broad, whole-body strategy for maintaining temperature and survival.
Thermoregulation is essential because mammals must keep their internal body temperature within a narrow range despite changing conditions outside the body. When an animal becomes cold, heat loss must be limited and heat production must increase. The body can constrict blood vessels in the skin, activate brown adipose tissue, induce skeletal muscle shivering and drive the animal towards a warmer environment. Cold can also alter feeding and energy use, while pleasant or mildly cool temperatures may engage reward circuits and influence dopamine release. How the brain combines these different reactions has remained unclear. The new work places the parabrachial nucleus at the centre of this puzzle, showing that a defined group of neurons responds to cold and links sensory information with physiological, behavioural, metabolic and affective adaptations.
To identify these cells, the researchers used activity-dependent genetic labelling in mice. This approach marks neurons that become active during a particular experience, allowing scientists to examine and manipulate the same population later. When mice were exposed to cold conditions, neurons in the parabrachial nucleus were labelled according to their activity. The resulting PB^Cold population showed rapid activation when temperatures fell, but the response did not quickly disappear. Instead, the neurons remained active across a broad range of cold stimuli, indicating that they may encode persistent environmental cooling rather than simply registering the instant at which temperature begins to drop. This sustained activity is important because thermoregulatory responses must continue for as long as the threat of heat loss remains.
The parabrachial nucleus is strategically positioned within the brain’s sensory and homeostatic networks. It receives information associated with the body’s internal state and external sensory conditions and can communicate with multiple downstream regions that control autonomic and behavioural functions. The study’s results indicate that PB^Cold neurons are primary recipients of cold sensory information in the brain. Their activity provides a possible neural explanation for how one environmental signal can produce many simultaneous outcomes. A drop in temperature can prompt brown fat to generate heat, blood vessels in the tail to constrict, muscles to shiver and the animal to seek shelter. Rather than treating these responses as independent circuits operating in parallel, the findings suggest that PB^Cold neurons help coordinate them as parts of a unified cold-defence programme.
The researchers tested this idea by silencing PB^Cold neurons, both temporarily and permanently. The consequences reached across several biological systems. When these neurons were inhibited, mice showed impaired activation of brown adipose tissue thermogenesis, a form of heat production that burns stored energy without requiring muscle contraction. Tail vasoconstriction was also disrupted, weakening a key mechanism that reduces heat loss from the body’s surface. Somatic responses were affected as well: the animals displayed impaired skeletal muscle shivering, another major source of heat when the environment becomes cold. Together, these results show that PB^Cold neurons are not simply associated with cold sensation. They are necessary for the effective deployment of multiple heat-preserving and heat-generating mechanisms.
The disruption extended beyond automatic physiology. Mice with silenced PB^Cold neurons also showed altered cold-avoidance behaviour, suggesting that the neural population helps translate temperature information into decisions about where to move. This behavioural response is crucial because avoiding cold can be more efficient than producing heat after exposure has already occurred. The neurons also influenced cold-induced hyperphagia, the increase in food intake that can accompany exposure to low temperatures. Eating more provides fuel for energy-intensive thermogenesis, linking appetite to thermal demand. In addition, silencing the cells affected dopamine release in response to rewarding cool stimuli. This finding connects the cold-sensing circuit to affective and motivational systems, indicating that the parabrachial pathway may help determine whether a temperature is experienced as threatening, tolerable or rewarding.
The importance of the circuit became especially clear under severe cold. Animals in which PB^Cold neurons were permanently silenced were less able to mount appropriate defensive responses and experienced compromised survival in extreme low-temperature conditions. This result elevates the cells from one component of a sensory pathway to a critical part of the machinery that protects the organism from environmental danger. The researchers also performed the opposite experiment. Activating PB^Cold neurons promoted warmth-seeking behaviour, increased food intake and raised energy expenditure. In other words, stimulating the population was sufficient to reproduce several hallmarks of a cold-response state, even without simply relying on the animal’s normal sensory experience. The bidirectional effects strengthen the conclusion that these neurons actively organize cold adaptation.
The study further examined the molecular identity of the PB^Cold population. Gene-expression profiling identified Grp and Trhr as highly specific markers for subsets of these neurons. The markers were not completely efficient, meaning that they label only portions of the full PB^Cold population, but their specificity could make them useful tools for studying the circuit in greater detail. Grp encodes gastrin-releasing peptide, a signalling molecule involved in neural communication, while Trhr encodes the thyrotropin-releasing hormone receptor, a receptor that can influence neuronal activity and endocrine-related pathways. The presence of these molecular signatures provides a route towards separating functionally distinct subgroups and determining whether particular neurons specialize in thermogenesis, vasoconstriction, shivering, feeding, avoidance or reward.
The findings also raise broader questions about how the brain represents temperature. A sensory signal is not necessarily a simple numerical readout of the environment. The sustained activity of PB^Cold neurons suggests that the nervous system may maintain a continuing representation of cooling, enabling downstream circuits to adjust their responses as long as thermal conditions demand it. At the same time, the broad effects of manipulating these neurons show that the representation is connected to competing priorities, including survival, energy availability and behavioural choice. Understanding this architecture could eventually help explain why disorders affecting temperature regulation often involve multiple symptoms at once. It may also illuminate how the brain balances the energetic cost of generating heat with the need to preserve body temperature.
By identifying PB^Cold neurons as a central hub for cold-induced homeostatic responses, the study adds a major piece to the neural map of thermal regulation. The work shows that a relatively defined population in the parabrachial nucleus can receive cold-related sensory information and coordinate responses ranging from brown-fat activation and shivering to appetite, environmental avoidance and dopamine signalling. The discovery does not reduce thermoregulation to a single circuit; rather, it reveals how diverse downstream systems can be organized around a shared sensory command. In an increasingly detailed picture of the brain’s control over the body, PB^Cold neurons emerge as a vital interface between the outside world and the internal fight to stay warm.
Subject of Research: Cold-activated parabrachial nucleus neurons and their role in coordinating thermoregulatory, behavioural, metabolic and affective responses.
Article Title: Parabrachial neurons orchestrate cold-induced homeostatic responses
Article References: Jung, S., Kondaurova, A., Lee, M. et al. Parabrachial neurons orchestrate cold-induced homeostatic responses. Nature Metabolism (2026). https://doi.org/10.1038/s42255-026-01565-1
Image Credits: AI Generated
DOI: https://doi.org/10.1038/s42255-026-01565-1
Keywords: thermoregulation, cold sensation, parabrachial nucleus, PBCold neurons, brown adipose tissue, shivering, vasoconstriction, cold avoidance, hyperphagia, dopamine, neural circuits, homeostasis
Tags: body’s homeostatic responses to coldbrainstem neuronscold thermoregulationintegration of cold sensory informationmammalian cold response mechanismsneural control of temperature and survivalneural coordination of temperature regulationneural pathways for cold detectionparabrachial nucleusPB^Cold neuronsthermoregulatory brain circuitswhole-body cold response strategy
