CrebB: Long-term Memories Are Made Of This

Our brains can store different types of memories. You may have forgotten what you had for lunch yesterday, but still be able to remember a song from your childhood. Short-term memories and long-term memories form via different mechanisms.

To establish long-term memories, the brain must produce new proteins, many of which are common to all members of the animal kingdom. By studying these proteins in organisms such as fruit flies, we can learn more about their role in our own memories.

Yves F Widmer, of the University of Fribourg, led a group that used this approach to explore how a protein called CrebB helps fruit flies to remember for several days that a specific odor is associated with a sugary reward. These odor-reward memories form in a brain region called the mushroom body, which has three lobes.

Input neurons supply information about the odor and the reward to the region, while output neurons pass on information to other parts of the fly brain. CrebB regulates the production of new proteins required to form these long-term odor-reward memories: but where exactly does CrebB act during this process?

Deactivating CrebB

Using a gene editing technique called CRISPR, Widmer et al. generated mutant flies. In these insects CrebB could be easily deactivated ‘at will’ in either the entire brain, the whole mushroom body, each of the three lobes or in specific output neurons.

The flies were then trained on the odor-reward task, and their memory tested 24 hours later. The results revealed that for the memories to form, CrebB is only required in two of the three lobes of the mushroom body, and in certain output neurons.

CrebB is dispensable for STM and MTM, but required for LTM.

CrebB is dispensable for STM and MTM, but required for LTM.
Credit: Widmer et al. CC-BY

Future studies can now focus on the cells shown to need CrebB to create long-term memories, and identify the other proteins involved in this process.

In humans, defects in CrebB are associated with intellectual disability, addiction and depression. The mutant fly created by Widmer et al. could be a useful model in which to investigate how the protein may play a role in these conditions.

Yves F Widmer, Cornelia Fritsch, Magali M Jungo, Silvia Almeida, Boris Egger, Simon G Sprecher
Multiple neurons encode CrebB dependent appetitive long-term memory in the mushroom body circuit
eLife 2018;7:e39196 DOI: 10.7554/eLife.39196

© 2018 eLife Sciences Publications Ltd. Republished via Creative Commons Attribution license. Top Image: Microscopy of the fruit fly brain. The CrebB protein (green) is found inside virtually all brain cells. In blue are the structures that connect different neurons together. Credit: Widmer et al. CC-BY 4.0