The Habenula Prevents Helpless Behavior in Larval Zebrafish

Abstract

Animals quickly learn to avoid predictable danger. However, if pre-exposed to a strong stressor, they do not display avoidance even if this causes continued contact with painful stimuli [1, 2]. In rodents, lesioning the habenula, an epithalamic structure that regulates the monoaminergic system, has been reported to reduce avoidance deficits caused by inescapable shock [3]. This is consistent with findings that inability to overcome a stressor is accompanied by an increase in serotonin levels [4]. However, other studies conclude that habenula lesions cause avoidance deficits [5, 6]. These contradictory results may be caused by lesions affecting unintended regions [6]. To clarify the role of the habenula, we used larval zebrafish, whose transparency and amenability to genetic manipulation enables more precise disruption of cells. We show that larval zebrafish learn to avoid a light that has been paired with a mild shock but fail to do so when pre-exposed to inescapable shock. Photobleaching of habenula afferents expressing the photosensitizer KillerRed causes a similar failure in avoidance. Expression of tetanus toxin in dorsal habenula neurons is sufficient to prevent avoidance. We suggest that this region may signal the ability to control a stressor, and that its disruption could contribute to anxiety disorders.

Habenular kisspeptin modulates fear in the zebrafish

“…The dHb L -silenced zebrafish show increased freezing in the course of a fear-conditioned assay (26,28), suggesting that this subnucleus is crucial for the modifications of behavior responses in an experience-dependent manner. A very recent study demonstrated that the dHb-interpeduncular nucleus silenced zebrafish exhibits intense innate fear expression, indicating a state of elevated baseline anxiety (29).…”

Olfactory projectome in the zebrafish forebrain revealed by genetic single-neuron labelling

“…Axons of OB output neurons terminate at the medialmost part of the neuropil domain in the rHb, presumably transmitting the odour information to the ventral part of interpeduncular nucleus. Two recent studies in zebrafish have shown that the Hb plays roles in controlling fear responses in experience-dependent manners 45,46 . However, it is tempting to speculate that the OB-rHb pathway may be a part of hard-wired circuits that mediate stereotyped responses such as innate behaviours, because the rHb receives strongly biased projections from particular glomerular clusters.…”

Zebrafish forebrain and temporal conditioning

“…For example, when adult goldfish were trained in a swimming task by pairing a 5 or 15 s light CS with an aversive US (an electrical shock), the fish displayed a response function (water displacement induced by fish activity) with a peak centred around the scheduled time of shock delivery following 200 training trials distributed across 20 sessions [61]. In a different CS-US aversive conditioning task, both adult [62] and larval [63] zebrafish acquired the CS-US contingency (less than 15 s) after about 10 conditioning trials. In this type of conditioning task, accurate timing is required to ensure that responses do not occur too early or too late, but are optimized.…”