Nicole Ireland ’20 and Grace Oxford ’20
When growing up, there are many new experiences that shape your likes and dislikes long into the future. One of the big factors is food. When you have a bad experience with a certain food or type of food, it changes the expression of your genes. Whether fish gave you food poisoning or you got sick with the flu after eating lasagna, that experience can stay with you for a long time and affect how you feel about tastes and smells. This is just one example of the way that our day to day lives can actually make changes to our genes.
Life’s experiences affect people in more ways they often realize due to their epigenome. The epigenome refers to all of the chemical changes that happen to our genes, determining which genes are able to be used. DNA is packaged tightly within cells to conserve space, but not all DNA is packaged in the same way. Similarly to packing a suitcase, you want to make sure that all the items you need right away are easily accessible, while the stuff you don’t need right now (or maybe ever) is secure and at the bottom. You might need those rain boots at some point, but if you’re headed to the Bahamas, best to keep them at the bottom, and filled with your socks. Similarly, DNA is packaged so that the DNA we need to use is open and available DNA whereas DNA not needed in the moment is tightly packed away. There is a wide range of modifications that can occur to change what DNA is available and when. It has been found that how our DNA is packed has connections to our learning and memory systems.
When talking about learning and memory, we split this process up into three general terms. First, acquisition refers to actually learning the information that gets stored as memory6. This happens during the first 30 seconds or so and helps us remember quick bits of information, like when you first hear a new phone number. Next, for about a day after acquisition, our brains work to consolidate that new information. You might repeat that phone number over and over in your head until you can write it down. This is the process of moving new information to an area of the brain where it can be stored. Finally, retrieval happens any time in the future when we want to use that information and we have to pull it out of storage. Retrieval is what happens every time you recite your childhood phone number from memory. Our brain can store some memories indefinitely which is referred to as our long-term memory.
When we combine two different things from our environment to create a memory involving both of them, we call this associative memory. Conditioned taste aversions are a specific type of associative memory where our brains pair the taste or smell of a certain food with the feeling of nausea and disgust4. After getting food poisoning from fish, more than likely you’re stuck with a nauseous feeling when smelling or tasting that same fish, long after the food poisoning has left your system.
The insula is a portion of our brain that is responsible for linking emotions and experiences which is why it is so important when we create taste-aversions. Conditioned taste aversions rely on the combination of information about the taste and smell of food with the negative effect it has on the body. If the insula is damaged, it can actually erase conditioned taste aversions2.Additionally, current research shows that when we stop the brain from being able to make new proteins in the insula, we also stop its ability to create taste aversions (Rodriguez-Blanco 2019). Even more interesting is that protein formation happens even after the memories have already been formed which demonstrates the importance of our brains continuing to make proteins for keeping our established memories.
(Sweatt et al 2013)
Creating these memories is essential for animals from an evolutionary perspective because it is important for survival to have strong memories of anything that can make us sick or potentially kill us. Food aversion mechanisms are almost identical in so many different species which tells us that they likely have been kept around during evolution. Animals form associative memories about food so quickly that it really only takes one experience of nausea for the memory to stick4. Many researchers think that organisms are set up to easily learn to associate nausea with food as a way to recognize poisons. Generally the things that we cannot digest are those that cause nausea, so this is our body’s way of making sure we never try to eat something that could hurt us again.
There are actually two separate biological mechanisms that can lead to learning food avoidance7. Sometimes we learn to not like a food because it makes us sick, while other times it’s because we learn to associate it with something bad. In our brain, these two events are treated completely differently even though they have the same end result – not liking that food anymore. In order to test this in laboratory settings, researchers often pair bitter or salty tasting things to induce nausea with the consumption of a certain food or drink. Associative learning, by pairing two things together, is relatively simple but results in long-term memories that can remain for the subject’s lifetime.
To study epigenetics in conditioned taste aversions, researchers wanted to find out more specifically what processes are happening in the insula and what happens if they mess with them? A common way that the environment decides what genes are ‘on’ versus which are ‘off’ is through processes called histone acetylation and deacetylation. Histone acetylation is commonly used to turn genes ‘on’ whereas histone deacetylation typically can be found in environments where the gene is being turned ‘off’. Researchers in one study chose to stop histone deacetylation from turning genes ‘off’ in the insula to see what would happen to an animal’s memory (Rodriguez-Blanco 2019). Their findings showed that stopping histone deacetylation kept genes ‘on’ in the insula and the animals had stronger memory formations (Rodriguez-Blanco 2019). They stopped this process both immediately after the animal learned and 7 hours post-learning and found that in both cases the memories were stronger. What this tells us is that epigenetic mechanisms are hard at work for a while after learning something; they don’t stop right after acquisition (Rodriguez-Blanco 2019).
There are chain-reactions that allow your brain to combine the information that makes associations to create taste aversions3. To test the effects of this, scientists studied the effects of this pathway on the epigenetics in snails. While an interesting choice of subject, the chain reactions happen in the snail brains very similarly as they do in ours due to the evolutionary reasons mentioned before. Through a conditioned taste aversion, the researchers were able to make snails dislike carrots, a food source previously considered a delicacy – the snails acted defensively toward carrots rather than eating them. Associating food with something nauseating starts a biological chain reaction which affects the epigenome by making certain DNA used for learning available to the brain3. When the chain reaction gets blocked somehow, it stops the memory formation process so the experience of pairing nausea with delicious carrots does not turn into a long-term memory. Interestingly, this pathway has only been shown to be important for learning negative food associations. You cannot use these techniques to learn to love a certain food. This implies that learning through negative experiences is fundamentally different from forming memories by other means, such as learning to associate a food with something good.
Another interesting way that epigenetics play a role in our creation of conditioned taste aversions is through the presence of a protein called brain derived neurotrophic-factor. This protein comes up pretty often and has been shown in modern research to help nerves grow and stay healthy 1. The thought process in studying brain derived neurotrophic-factor for conditioned taste aversions is that adding more of it to the insula could theoretically make stronger memories. To test this in the lab, researchers are able to force mice to have taste aversions by adding a little bit of LiCl to their food, which causes them to get sick to their stomachs. Using this method, researchers split the mice into two groups; a group with a weak conditioned taste aversion and a group with a really strong taste aversion1. Then, by adding brain derived neurotrophic-factor to the insula in the group with the weak taste aversion, they were able to make up for the difference between the two groups1.This is really interesting because one could theoretically create food aversion memories in one’s brain by adding the brain derived neurotrophic factor at the right time and place.
So, if you have a learned food aversion, are you stuck with it for the rest of your life? In recent years, epigenetic research has shown that memory acquisition and consolidation are not fixed, unchanging processes but can be influenced by the environment of our genes. Due to its epigenetic bases, food aversions can be formed and rewritten quickly and easily in comparison to some other behaviors. Scientists have found substances that can stop long-term memories of food aversions forming, but cannot reverse food aversions already learned. So while a chemical associated with feeding behavior, FMRF, has been shown to stop memories from forming by packing the DNA needed more tightly3, I do not recommend using it to get rid of a food aversion you have.
While there are clear evolutionary benefits to forming conditioned taste aversions for animals in the wild who need to avoid poisonous foods for their safety, they often come as a nuisance for humans. Certain foods that left us with food poisoning or things we ate right before catching the stomach flu often stick with us for years to come; even just the smell resulting in disgust. Considering food-related problems that many people struggle with, like eating disorders or addictions, it is really interesting to consider the implications of this type of research. It’s possible that with further research, scientists could use their knowledge of conditioned taste aversions to develop therapeutic treatments for these types of disorders. Epigenetic mechanisms that influence the formation and maintenance of aversion memories are interesting to study in order to understand why some associations are made while others aren’t and why they last as long as they do. With knowledge about these mechanisms, scientists are potentially able to create, over exaggerate, and inhibit these associations artificially even after the memory has been acquired.
- Martinez-Moreno, A., Rodriguez-Duran, L. F., & Escobar, M. L. (2016). Brain-derived neurotrophic factor into adult neocortex strengthens a taste aversion memory. Science Direct, 297, 1-4.
- Gogolla, N. (2017, June 19). The insular cortex. Current Biology, 27, 580-586.
- Grinkevich, L N. (02/2014). Epigenetics and the Formation of Long-Term Memory. Neuroscience and Behavioral Physiology, 44(2), 200–213. Boston: Springer US.
- Sweatt, J. D. (2010). Mechanisms of memory (2nd ed.). Elsevier.
- Sweatt, J. D., Meaney, M. J., Nestler, E. J., & Akbarian, S. (Eds.). (2013). Epigenetic regulation in the nervous system. Elsevier.
- Tronson, N. (Presenter). (2018, September 6). Synapses, circuits, neuroanatomy, phases of memory. Lecture presented at The University of Michigan, Ann Arbor, MI.
- Wright, G. A., Mustard, J. A., Simcock, N. K., Ross-Taylor, A. A., McNicholas, L. D., Popescu, A., & Marion-Poll, F. (2010). Parallel reinforcement pathways for conditioned food aversions in the honeybee. Current biology : CB, 20(24), 2234–2240. https://doi.org/10.1016/j.cub.2010.11.040