In a groundbreaking study, scientists discovered that the brain forms “cold memories” which can later trigger increased metabolism even without a drop in temperature.
By training mice to associate specific visual cues with cold environments, the researchers showed that the animals began heating themselves in anticipation of cold, driven by brain-stored memories. They pinpointed these cold memories to engram cells in the hippocampus and demonstrated that stimulating these cells could artificially activate thermogenesis. This exciting work opens up potential therapeutic strategies for conditions like obesity and cancer by harnessing learned thermal regulation and highlights the deep connections between memory, behavior, and metabolism.
Brain Forms “Cold Memories” That Influence Metabolism
New research led by Professor Tomás Ryan at Trinity College Dublin reveals that the brain forms lasting memories of cold experiences and uses them to regulate metabolism. This is the first study to demonstrate that the brain not only encodes cold-related memories but also uses them to influence how the body manages heat, a process known as thermoregulation.
The findings could have far-reaching implications for developing treatments for conditions such as obesity and cancer, where disrupted metabolism or thermoregulation plays a role. The research also opens new avenues for exploring how memory influences broader aspects of behavior and emotional processing.
Classical Conditioning and the Birth of Behavioral Memory
The idea that experiences can shape future responses is rooted in classical conditioning, first described by physiologist Ivan Pavlov in 1897. Pavlov showed that animals could learn to associate unrelated stimuli, like a bell, with meaningful outcomes, such as food, triggering a physiological response. This form of learning, now known as Pavlovian conditioning, remains foundational in neuroscience and psychology.
In the brain, long-term memories are stored as networks of connected neurons called engrams. Scientists are increasingly identifying engrams not just for abstract thoughts or events, but also for physical experiences, such as illness, inflammation, eating, and pain, suggesting that the brain keeps detailed records of the body’s interactions with its environment.
Hypothesizing Temperature Memory Engrams
The researchers behind this work hypothesised that the brain may form engrams for temperature representations, and that these would serve to help an organism survive in changing temperatures. But to identify these engrams, they first had to test whether cold memories could form in the first place.
While memories are generally measured as changes in animal behaviour, the Ryan Lab collaborated with Prof. Lydia Lynch (then at Trinity College Dublin, now at Princeton University). They focused on metabolism as a first-order readout of cold experience, because mammals are known to increase their metabolism to create heat in the body when the environment is cold, via a process of adaptive thermogenesis.
Mice Trained to Predict and React to Cold
Lead author of the article published today in the leading international journal, Nature, Dr. Andrea Muñoz Zamora, successfully trained mice to associate a cold experience of 4 °C with novel visual cues that were only present in designated cold contexts. After a few days, mice were presented with the visual cues in the same context, but at room temperature. Crucially, the team discovered that the animals would upregulate their metabolism to induce predictive thermogenesis when they were “expecting” the environment to be cold.
Having established that mice could form memories of cold experiences, the team then delved into how this was happening in the brain. Using activity-dependent gene labelling, the scientists were able to genetically hitchhike onto the engram cells coding for the cold memory in a brain region known as the hippocampus. Remarkably, when these cold engram cells were artificially stimulated (using a technique called optogenetics), the mice increased their metabolism in order to generate heat. And in a converse experiment, to double-check the central finding, when cold engram cells were inhibited, the mice were unable to express cold memories in response to the conditioned visual cues.
The Brain’s Role in Controlling Fat and Heat
Dr. Muñoz Zamora, said: “We discovered that when mice are exposed to a cold temperature they form memories that allow them to up-regulate their body’s metabolism when they anticipate cold experiences in the future.”
Prof. Lynch added: “A large part of this learned control of body temperature seems to be due to increased activity of brown adipose tissue – or brown fat – which can be controlled by innervations originating in the brain. Our brain must learn from the bodily experiences of cold, but then feeds back to control how our fat cells respond to cold.”
Dr. Aaron Douglas, who was joint lead author on the study, said: “Numerous clinical disorders, ranging from obesity to forms of cancer, may be treated by manipulating thermoregulation through brown adipose tissue. In the future, it will be important to test whether the manipulation of cold memories in humans could provide novel avenues for altering metabolism for therapeutic purposes.”
Broader Implications for Brain, Emotion, and Behavior
This research opens many new doors for further discovery research, as well as the development of treatments. Understanding how representations of cold experiences affect broader brain functions such as emotion, decision-making, and social behaviour will provide insights into the embodied nature of the mind, for example.
“The sophisticated aspects of our minds evolved from more basic, visceral, bodily representations,” said Prof. Ryan. “Understanding how these components of our brain affect our behaviour in general is crucial to understanding our emotions and our use of memory.”
“This integrative piece of work offers a quintessential example of inter-disciplinary science. Neuroscience requires collaboration and it was the synergy with Prof. Lynch that allowed the unusual combination of memory engram work with metabolism research.”
Reference: “Cold memories control whole-body thermoregulatory responses” by Andrea Muñoz Zamora, Aaron Douglas, Paul B. Conway, Esteban Urrieta, Taylor Moniz, James D. O’Leary, Lydia Marks, Christine A. Denny, Clara Ortega-de San Luis, Lydia Lynch and Tomás J. Ryan, 23 April 2025, Nature.
DOI: 10.1038/s41586-025-08902-6
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3 Comments
thank you for this
I am a medical anthropologist researcher and author, and outspoken critic of animal research. This study is an example of psychopathy and what is wrong with animal research. “We discovered that when mice are exposed to a cold temperature they form memories that allow them to up-regulate their body’s metabolism when they anticipate cold experiences in the future.” These researchers cruelly “trained mice to associate a cold experience of 4 °C with novel visual cues that were only present in designated cold contexts.” In other words, they nearly froze the poor mice while giving them a visual cue to associate with the pain they were suffering. Imagine being exposed to near freezing water and the shock and fear it would create. That happens in rodents, too. “After a few days, mice were presented with the visual cues in the same context, but at room temperature. Crucially, the team discovered that the animals would upregulate their metabolism to induce predictive thermogenesis when they were “expecting” the environment to be cold.” In other words, they were so frightened and anxious by that near death freezing that they freaked out when seeing the visual cue, and began to make heat. Of course, this is torture, and their response is not normal, and some of the heat is from anxiety and stress.
This inhumane research is unacceptable, unscientific, and psychopathic. DOGE, Sec. Kennedy, please cut the funding of this cruel, useless research!
See also my article, Of Mice and Men, The Problem with Studying Mice to Learn about Men. https://www.academia.edu/127948044/Of_Mice_and_Men_The_Problems_with_Studying_Mice_to_Learn_about_Men
I wonder if that is part of the cold-adaptation encountered amongst the now-deceased Yaghan “indians” of Patagonia and that developed amongst assorted European explorers of the Antarctic and Arctic, not to mention the countless sailors of the sailing-ship era.
I never did get fat working at minus umpteen degrees Celsius.