Memories can control metabolism, research demonstrates

New multidisciplinary research led by Prof Tomás Ryan from Trinity College Dublin shows that the brain forms memories of cold experiences and uses them to control our metabolism. This study is the first to show that cold memories form in the brain – and map out how they subsequently drive thermoregulation.

The discovery may have important applications in therapies designed to treat a range of disorders – from obesity to cancer – in which thermoregulation and metabolism (or a lack of control in this area) plays a role, as well as opening the door to more fundamental research, which could help us better understand how memories impact our behaviour and emotions.

In 1897, the physiologist Ivan Pavlov first described classical conditioning, where animals and humans form associations between different aspects of the environment. He showed that dogs could be trained to salivate in hopeful anticipation of food, when an associated bell was rung. Classical or Pavlovian conditioning has since become a core staple of neuroscience and psychology.

Long-term memories are stored in the brain as ensembles of inter-connected cells, termed engrams. Increasingly, modern neuroscience is beginning to identify engrams that encode for bodily representations, such as experiences of infection; inflammation; food consumption; and pain. 

The researchers 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 identity these engrams they first had to test whether cold memories could form in the first place. 

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.

Lead author of the article published in Nature, Dr Andrea Muñoz Zamora, successfully trained mice to associate a cold experience of 4oC 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.