Discovery of the 'Cold Neuron' in the Brain...Regulation of Cold Response and Energy Expenditure [Reading Science]

Professor Sungyeon Kim's Team at Seoul National University Identifies Parabrachial Nucleus Neurons That Receive Cold Sensation from the Skin
Activation Increases Heat Production and Energy Expenditure
New Insights for Obesity and Thermoregulatio

When exposed to cold environments, the body responds by constricting skin blood vessels and shivering to generate heat. People instinctively seek warm places, and prolonged exposure to cold results in increased appetite. The identity of the “cold neuron” in the brain, which orchestrates these various cold responses simultaneously, has now been uncovered.

The research team led by Professor Sungyeon Kim from the Department of Chemistry at Seoul National University’s College of Natural Sciences announced on August 13 that they have identified the function of a core group of neurons called the “parabrachial nucleus cold neuron (PB Cold neuron).” These neurons are the first to receive cold information detected by the skin and regulate the body’s whole cold response.

It was previously known that neurons in the parabrachial nucleus (PB), located in the hindbrain, respond to cold and, to some extent, contribute to body temperature regulation. Instead of identifying candidates based on specific genes or neural circuits, the research team defined “parabrachial nucleus cold neurons” by tracking neurons actually activated when mice were exposed to cold.

A schematic diagram showing the process in which cold information detected by the skin is transmitted to the brain's 'Parabrachial nucleus Cold neuron (PB Cold neuron)', inducing whole-body cold responses such as brown adipose tissue thermogenesis, blood vessel constriction, muscle shivering, seeking warmth, and increased appetite and energy expenditure. Provided by the research team.

These neurons became rapidly and persistently activated as the surrounding temperature dropped. When the researchers inhibited or eliminated these neurons, brown fat thermogenesis, skin vasoconstriction, muscle shivering, as well as cold-induced behaviors like seeking warmth and increased appetite, all weakened. Under severe cold, the survival ability of the mice was significantly reduced.

Conversely, artificial activation of these neurons caused mice to behave as though they were exposed to cold, even when the ambient temperature did not decrease. The mice sought out warmer places and increased their heat production via brown fat. In other words, simply providing a “cold” signal to the brain triggered multiple cold-defense responses simultaneously.

The research team also confirmed that the cold signaling pathway in the brain is involved not only in prompting avoidance of cold but also in the brain’s assessment of pleasantness or unpleasantness regarding temperature. When mice in a hot environment were supplied with cool air, dopamine was released in the brain’s reward circuit. However, when the parabrachial nucleus cold neurons were inhibited, this dopamine response was greatly diminished.

When these neurons were artificially activated in a hot environment, heat-dissipating behaviors such as the mice stretching out their bodies decreased. Although the actual ambient temperature remained the same, the cold signal to the brain caused mice to perceive the heat as less uncomfortable, resulting in behavioral changes.

Increased Food Intake Without Weight Gain... Discovery of an Energy Expenditure Circuit

One particularly noteworthy finding is the observed metabolic changes. When the research team continuously activated the parabrachial nucleus cold neurons in mice for four weeks, food intake increased; however, their body weight did not. Oxygen consumption and overall energy expenditure rose, brown fat (which produces heat) increased, and the size of white fat cells decreased.

This suggests a novel approach to metabolic regulation by using the brain’s neural circuits to increase energy expenditure, as opposed to existing obesity treatments that mainly suppress appetite. However, since activation of the cold neurons also leads to increased appetite, it is not yet at a stage where it could be directly used for obesity treatment. The research team explained that further studies are needed to determine whether only the energy consumption pathway can be selectively controlled in the future.

This research also provides clues for understanding thermoregulatory disorders and heat-related illnesses. It demonstrated at the level of a specific group of neurons that the brain’s interpretation of temperature information from the skin can lead to different whole-body reactions involving blood vessels, muscles, metabolism, and behaviors. However, the researchers noted that this study is basic research conducted with mice and did not directly test therapeutic effects on heat-related illnesses.

The research team validated the function of the parabrachial nucleus cold neurons using activity-dependent neuronal labeling, optogenetics, chemogenetics, real-time neural activity measurement, electromyography, and metabolic rate evaluations.

The results of this study, jointly authored by Ph.D. candidate Sieun Jung and master's student Anna Kondaurova from Professor Kim’s team, were published online on August 13 in the international journal “Nature Metabolism.”

This content was produced with the assistance of AI translation services.