Subterranean Fishes of the World

4275

2019

AIM 2019

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Cavefish (CF) present complex behavioral changes: increased locomotor activity, loss of aggressiveness and schooling, and reduced sleep. This corresponds to the “cavefish behavioral syndrome”. We aim at understanding the genetic and neural bases of the behavioral adaptation of A.mexicanus to the cave environment. Our group has previously described a coding point mutation in the Pachón CF gene encoding Monoamine Oxidase (MAO), the serotonin degrading enzyme (Elipot et al., Nature Comms 2014). With protein structure 3D modelling, we now found that this mutation changes the orientation of residues at the entrance of the active site. This structural change is probably responsible for the two- fold reduction of the MAO activity, and subsequently increased serotonin level in CF brain. To generate a phylogeographic map of MAO mutated alleles, we genotyped 195 CF and 437 SF from various caves and rivers. The exact same mutated MAO allele (P106L) was present in 5 different cave populations in the Sierra de El Abra, and was not fixed in most of them including in the Pachón cave. The pro106leu allele was not found in SF samples examined. However, another point mutation (M107I) was discovered, showing that polymorphism in the MAO gene does exist in the SF population. As accumulated evidences suggest that changes in neuro-modulatory systems generate significant variations in complex behaviors, we then addressed the following question: what are the consequences of the MAO mutation at the level of the serotonergic system and the behavior in Pachón CF? We thus compared the behaviors and brain monoamine levels of SF, CF with or without the mutation obtained by crosses, as well as SF MAO knock-out obtained by CRISPR-Cas9 genome editing. We found that the differences in the levels of serotonin (5HT) and dopamine (DA) between SF and CF was exclusively due to the MAO mutation in CF. The mutation also increased epinephrine and norepinephrine levels respectively, in the body and the brain. Unexpectedly, the mutation did not seem to be responsible for the loss of aggressiveness and schooling in CF, but it increased hyperactivity in a novel tank. These results will be discussed.

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