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Tuesday, March 24, 2015

A new player in the neural learning circuit!

Zebrafish have also become an ideal model for studying vertebrate neuroscience and behavior. "Normal fish startle with changes in noise and light level by bending and swimming away from the annoying stimuli. They do eventually habituate and get used to the alterations in their environment. However, fish mutants fail to habituate -- they never get used to their surroundings and always flinch at the loud noises."
Scientists developed Zebrafish mutants and exposed them to the startle response test. Most fish larvae habituated and stopped reacting to the noise stimulus. Some of the mutants, did, however, fail to habituate and continued to respond to the noise.
One of the mutants was vertebrate-specific gene pregnancy-associated plasma protein-aa (pappaa). This gene encodes an enzyme that cleaves other proteins and works outside the cell. It is known to increase the availability of the hormone IGF at the cell surface, thereby enhancing receptor signaling for the IGF pathway.
A role of the PAPPAA enzyme in or on neurons had not been described; however, IGF is known to be an important molecule in pathways that determine long-term memory.
The team verified the involvement of the IGF pathway by rescuing mutant behavior to normal by adding an activator of downstream molecules that interact with the IGF receptor. Mutants that were treated this way, when put back in the startle test, reacted normally and habituated to the loud noise. Also, when the team used an inhibitor of the IGF receptor in normal zebrafish larvae, these fish showed the same behavior in the startle test as the pappaa mutants. This all indicates that the pappaa gene promotes learning by acutely and locally increasing IGF availability to the cell.