Modulation of Neural Circuits by the Neuropeptide, Arginine Vasotocin, in the Central Nervous System of Zebrafish.

Abstract

The mammalian neuropeptide arginine vasopressin (AVP) has been linked to a wide variety of complex social behaviors in mammalian species. The neuropeptide changes behaviors presumably by modulating neural circuits via V1a receptor signaling. However, due to the extreme complexity of the large mammalian brain and array of complex behaviors it generates, the mechanism by which AVP modulates neural circuits is still poorly understood. To better understand the mechanism, we decided to study the non-mammalian homologue of AVP, arginine vasotocin (AVT) in the brain of zebrafish, a popular vertebrate model species with a simpler brain and simpler behaviors. The major goal for the research was to gain mechanistic insights into how the neuropeptide modulates behaviors. We first cloned the cDNA of two V1a-like receptors, avtr1a1 and avtr1a2, and conducted in situ hybridization to examine the location of avtr expression in the brain. To our surprise, both receptors are expressed in the CNS during embryogenesis prior to the appearance of any complex social behaviors. Given the anatomical location of the avtr expression, we hypothesized that avt/avtr signaling modulates embryonic sensorimotor behaviors. In fact, the pharmacological increase of avt enhanced, and anti-sense morpholino knockdown of avt, avtr1a1, and avtr1a2 genes disrupted embryonic sensorimotor behaviors. We also found that chemosensory stimuli that induce locomotor responses activate avtr+ neurons in the posterior hindbrain, further supporting the hypothesis that avtr+ neurons modulates sensorimotor responses. Moreover, we examined the expression patterns of avtrs in the adult zebrafish brain via whole brain in situ hybridization to better understand how avt/avtr signaling modulates adult social behaviors. In fact, both avtrs are expressed in brain regions known to modulate social behaviors including aggression and fear responses. We also investigated inter-male aggressive interaction that is repeatedly linked to avt signaling across species, and how the aggressive acts get modulated in large social groups. As a whole, the current study gives mechanistic insights into how the neuropeptide modulates both early and mature vertebrate behaviors.