PgmNr Z549: Asymmetric activation of the dorsal habenulae correlates with larval recovery from electric shock.

Authors:
E. R. Duboué 1 ; E. Hong 2 ; A. Muto 3,4 ; K. Kawakami 3,4 ; M. E. Halpern 1


Institutes
1) Carnegie Institution for Science, Baltimore, MD; 2) Laboratoire Neurosciences Paris Seine, INSERM UMRS 1130, UMR 8246 Université Pierre et Marie Curie 75252 Paris, France; 3) Division of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Shizuoka, Japan; 4) Department of Genetics, The Graduate University for Advanced Studies (SOKENDAI) Mishima, Shizuoka, Japan.


Abstract:

Owing to their differences in size, gene expression and connectivity, the dorsal habenulae (dHb) of larval zebrafish can be used to assess the significance of left-right (L-R) asymmetry of the brain on behavior. In particular, we discovered a differential response between the left and right dHb to a fearful stimulus, mild electric shock.  Following shock, wild-type larvae freeze for a short period of time (10-15 sec) before swimming again. Whole body cortisol levels, as measured in groups of larvae, also increase in response to electrical stimulation. Optogenetic activation of the dHb decreases the length of freezing, indicating that this brain region expedites the recovery from an aversive stimulus. Using in vivo calcium imaging in head affixed larvae, we identified an asymmetric population of neurons, whose activation is temporally correlated with recovery from shock.  Consistent with more neurons in the left dHb modulating the response, unilateral severing of a major axonal pathway from the left but not the right dHb results in increased freezing behavior. Larvae with L-R reversed asymmetry or with right isomerized dHb also show a significant increase in freezing duration, as well as higher cortisol levels compared to controls. Moreover, neural activation in response to shock is not detected in the dHb by calcium imaging of these larvae. By contrast, larvae with left isomerized dHb exhibit a similar period of freezing as their wild-type siblings but an equivalent number of neurons are activated in both dHb. The data suggest that a neuronal population, which predominates in the left dHb, mediates fear responses in larval zebrafish.