Induction - reversal modeling of psychiatric disorders by functional manipulation of habenular pathways in zebrafish

The etiomechanism of psychiatric disorders is still poorly understood. Optogenetically induced changes in neural networks and consequent change of behavior in transgenic animals has provided a novel opportunity to develop animal models of various psychiatric disorders. We hereby propose zebrafish as a model organism based on the premise of its comprehensive similitude with the mammalian brain. The habenula is an evolutionarily conserved bilateral structure located at the interface of diencephalon, basal nuclei and brainstem working as a gateway between cortical-subcortical and brainstem structures. Many studies have suggested master role of habenula in control of adaptive behavior through regulation of brainstem aminergic nuclei. It is thought to function as a switchboard for regulating emotional behavior in conditions facing survival challenges. The dysregulation of the emotional behavior has been at the base of psychiatric disorders and a functional manipulation of specific habenular nuclei using optogenetics combined with incremental levels of stress challenge may prove to be a basic model for the genesis of psychiatric disorders. Conversely, reversing the manipulation, scaling down stress levels, and providing enriched environment may ease psychiatric symptoms. The present article has proposed a hypothesis on the development of a basic zebrafish model for the psychiatric disorders based on this concept. Such a model may be of great help in understanding the common mechanism involved in genesis and progression of various psychiatric disorders. The article has also elaborated on the operational mechanisms and validity of the methodology and has suggested an experimental design for the proposed study model.