Research Unveils How Cold Experiences Shape Metabolism in Mice

A team of interdisciplinary researchers, led by Prof. Tomás Ryan from Trinity College Dublin, has revealed that the brain not only forms memories of cold exposure but also harnesses these memories to regulate metabolic processes. This groundbreaking study marks the first of its kind to explore the relationship between cold experiences and memory formation, specifically focusing on how such memories influence thermoregulation.

The implications of this research are significant, particularly in developing therapies aimed at treating various conditions, including obesity and cancer, where metabolic regulation is a critical factor. Furthermore, this study paves the way for deeper inquiries into the fundamental question of how memories shape our behaviors and emotional responses.

In the late 19th century, physiologist Ivan Pavlov introduced the concept of classical conditioning, which describes how organisms associate environmental cues with specific outcomes. Pavlov’s experiments with dogs showed that animals could learn to anticipate food when prompted by a bell, laying a foundation for the fields of neuroscience and psychology.

Current neuroscientific understanding points to the existence of long-term memories being encoded in the brain as ensembles of interconnected neurons known as engrams. Recent advancements in the field have focused on identifying engrams associated with bodily experiences such as pain, hunger, inflammation, and even infections.

The research team hypothesized that the brain might also form engrams related to temperature sensations to enhance survival in varying environmental conditions. However, before confirming this, they needed to validate the creation of cold memories.

Typically, memory formation is assessed through observable changes in behavior. The Ryan Lab collaborated with Prof. Lydia Lynch, now at Princeton University, focusing on metabolic responses as a direct indicator of cold memory formation. Mammals are known to increase energy expenditure through adaptive thermogenesis in response to cold environments.

Lead author Dr. Andrea Muñoz Zamora and her colleagues successfully conditioned mice to associate a temperature of 4°C with specific visual cues presented only in cold settings. When reintroduced to these visual cues in a neutral environment at room temperature, the mice showed a notable increase in metabolic activity, indicative of predictive thermogenesis in anticipation of cold exposure.

After confirming that mice could indeed develop cold-related memories, the researchers investigated the underlying processes in the brain. They employed activity-dependent gene labeling to identify the engram cells associated with cold memory, focusing on the hippocampus. Impressively, stimulating these cold memory engram cells caused the mice to boost their metabolism to generate heat. Conversely, inhibiting these cells prevented the mice from recalling the cold memory when faced with the relevant visual cues.

Dr. Muñoz Zamora emphasized, “Our findings indicate that exposure to cold results in memory formation, enabling the organism to enhance metabolic activity in anticipation of future cold encounters.”

Prof. Lynch further elaborated on the findings, stating, “The ability to learn and control body temperature appears largely driven by enhanced activity in brown adipose tissue, influenced by brain signals. Our brains learn from cold experiences and subsequently regulate how our fat cells respond to such exposure.”

Dr. Aaron Douglas, a joint lead author of the study, noted the potential of this research to impact clinical treatments for various disorders, suggesting that manipulating cold memory pathways might offer innovative strategies for altering metabolism therapeutically.

This study opens numerous avenues for future research and the potential development of effective treatments. Gaining a deeper understanding of how memories of cold exposure influence broader brain functions, including emotions, decision-making, and social interactions, will shed light on the embodied nature of our cognitive processes.

Prof. Ryan remarked on the interdisciplinary nature of this research: “The sophisticated workings of our minds stem from more primitive bodily representations. Understanding how these elements influence our behavior is crucial for grasping the full spectrum of our emotional experiences and mnemonic functions.”

He also highlighted the collaborative essence of this research, stating, “This integrative effort is a testament to the power of interdisciplinary science. Collaboration in neuroscience is vital, and it was the partnership with Prof. Lynch that brought together the unique aspects of memory engram analysis and metabolic research.”