The habenula prevents helpless behavior in larval zebrafish |
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Authors: | Lee Aletheia Mathuru Ajay S Teh Cathleen Kibat Caroline Korzh Vladimir Penney Trevor B Jesuthasan Suresh |
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Institution: | 2. Department of Psychology, National University of Singapore, 9 Arts Link, Singapore 117570;3. Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673;4. Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543;5. Department of Physiology, National University of Singapore, 2 Medical Drive, Singapore 117597;6. Neuroscience and Behavioral Disorders Program, Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857 |
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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. |
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