Habenula, lateralisation and conflict resolution

habenula 2

Image taken from http://journal.frontiersin.org/article/10.3389/fnins.2011.00138/full

Although the zebrafish has already been established as a model organism to investigate the genetic and neurological basis of aggression the circuits in the brain that control this behaviour are still not well understood. One area of the brain that has been intensively studied is the dorsal habenula, which shows a striking asymmetry in organisation, gene expression and connectivity between the left- and right halves of the brain. The habenula is also located superficially in the zebrafish brain (making it easy to access) and also controls lateralised behaviours. For example, adult zebrafish prefer use the right eye to examine novel objects whereas the left eye is used to look at familiar objects (Barth et al., 2005). Furthermore, disrupting habenula symmetry makes adult zebrafish more anxious (Facchin et al., 2015).
The habenula has already been implicated in fear conditioning as part of a circuit that send projections to the interpeduncular nucleus (IPN) and the dorsal tegmental area (equivalent to the periaqueductal grey matter in mammals) via the raphe nucleus, the most prominent source of 5-HT in the vertebrate brain (Chou et al., 2016).
In a recent study Chou and colleagues used state of the art techniques to investigate conflict resolution (winning or losing bouts of aggression) in zebrafish, with a particular focus on the habenula (Chou et al., 2016). The authors used calcium imaging to visualise neural activity and uncovered differential activation of the habenula circuitry. Fish which either won a fight or were not exposed to aggression showed calcium signals in the lateral dorsal habenula and dorsal IPN, whereas fish who lost a fight – “losers” – showed medial dorsal habenul and ventral IPN activity.
In a next set of experiments, Chou et al used genetic tricks (Gal4:UAS lines targeted to specific neurons driving expression of tetanus neurotoxin to block firing) to silence habenula activity and then watched fish fight. Silencing of the lateral dorsal habenula increased the chances that a fish would lose a fight whereas blocking medial lateral habenula activity increased the number of fights won. In all cases examined there were no changes to other behaviours including locomotion and anxiety; differential habenula activation really does seem to underlie fighting ability!
Taken in a wider context, this is an impressive study because the habenula-IPN-DTA circuit seems to act a switch for aggression. It seems likely that a balance between activation of two pathways – either at the level of the habenula itself, or between neurons in the IPN – controls the outcome of social interactions. Alterations to the habenula have been linked to several psychiatric disorders such as major depression, ADHD and schizophrenia. Further studies looking at lateralised brain activity may even shed light on the symptoms of some human diseases.


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