Viral-mediated transgenesis of MAOA and AVP increases territorial aggression in stickleback

Establishing a causal relationship between genes and social behavior is challenging. To enable direct manipulation of candidate genes and thereby examine how their expression contributes to behavior, we developed a neurosurgical method to deliver pharmacological agents or transgenic elements directly into the threespine stickleback (Gasterosteus aculeatus) brain. Threespine sticklebacks are a classic system for the study of behavior, ecology, and evolution. Male sticklebacks defending nesting territories are highly aggressive toward intruders. Previous studies in stickleback have shown that aggression is heritable, and that hundreds of genes are differentially expressed in the brain following territorial intrusion. We use viral-mediated transgenesis to test the effects on territorial aggression of overexpression of candidate genes, monoamine oxidase (MAOA) and arginine vasopressin (AVP), in the stickleback brain. Male sticklebacks received transcranial injections of mammalian homolog cDNA packaged in a replication-deficient Herpes Simplex Virus 1 carrier. Animals transfected with either AVP or MAOA constructs were more aggressive in response to a territorial intruder, unlike control animals transfected with a fluorescent protein. Viral-mediated transgenesis is a promising method to examine genetic underpinnings of behaviors. Our success demonstrates that widely available mammalian plasmids work with this method, lowering the barrier of entry to the technique. This method is flexible, fast, and amenable to statistically powerful within-subject experimental designs, making it practical for use in natural populations. It further enhances the growing molecular toolkit in threespine stickleback, a classic ethological system, and is the first step toward using chemogenetics and optogenetics. Major Findings Forced expression of MAOA or AVP resulted in more attacks, showing a causal link between genes and behavior.