The habenula is crucial for experience-dependent modification of fear responses in zebrafish

Agetsuma, Masakazu; Aizawa, Hidenori; Aoki, Tazu; Nakayama, Ryoko; Takahoko, Mikako; Goto, Midori; Sassa, Takayuki; Amo, Ryunosuke; Shiraki, Toshiyuki; Kikuchi, Kôichi; Hosoya, Toshihiko; Higashijima, Shin‐ichi; Okamoto, Hitoshi

doi:10.1038/nn.2654

Cited by 346 publications

(399 citation statements)

References 15 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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Chemotopic odour representations in the olfactory bulb are transferred to multiple forebrain areas and translated into appropriate output responses. However, a comprehensive projection map of bulbar output neurons at single-axon resolution is lacking in vertebrates. Here we unravel a projectome of the zebrafish olfactory bulb through genetic single-neuron tracing and image registration. We show that five major target regions receive distinct modes of projections from olfactory bulb glomeruli. The central portion of posterior telencephalon receives non-selective, interspersed inputs from all glomeruli, whereas the ventral telencephalon is diffusely innervated by axons from particular glomerular clusters. The right habenula and posterior tuberculum (diencephalic nuclei) receive convergent inputs from restricted and all glomerular clusters, respectively. The bulbar recurrent projections are coarsely topographic. Thus, the primary chemotopic organization is transformed into distinct sensory representations in higher olfactory centres. These findings provide a framework to understand general principles as well as species-specific features in decoding of odour information.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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“…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).…”

Section: Discussionmentioning

confidence: 99%

Habenular kisspeptin modulates fear in the zebrafish

Ogawa

Nathan

Parhar

2014

Proc. Natl. Acad. Sci. U.S.A.

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Kisspeptin, a neuropeptide encoded by the KISS1/Kiss1, and its cognate G protein-coupled receptor, GPR54 (kisspeptin receptor, Kiss-R), are critical for the control of reproduction in vertebrates. We have previously identified two kisspeptin genes (kiss1 and kiss2) in the zebrafish, of which kiss1 neurons are located in the habenula, which project to the median raphe. kiss2 neurons are located in the hypothalamic nucleus and send axonal projections to gonadotropin-releasing hormone neurons and regulate reproductive functions. However, the physiological significance of the Kiss1 expressed in the habenula remains unknown. Here we demonstrate the role of habenular Kiss1 in alarm substance (AS)-induced fear response in the zebrafish. We found that AS-evoked fear experience significantly reduces kiss1 and serotonin-related genes (plasmacytoma expressed transcript 1 and solute carrier family 6, member 4) in the zebrafish. Furthermore, Kiss1 administration suppressed the AS-evoked fear response. To further evaluate the role of Kiss1 in fear response, zebrafish Kiss1 peptide was conjugated to saporin (SAP) to selectively inactivate Kiss-R1-expressing neurons. The Kiss1-SAP injection significantly reduced Kiss1 immunoreactivity and c-fos mRNA in the habenula and the raphe compared with control. Furthermore, 3 d after Kiss1-SAP injection, the fish had a significantly reduced AS-evoked fear response. These findings provide an insight into the role of the habenular kisspeptin system in inhibiting fear.5-HT | interpeduncular | neuroendocrine | anxiolytic K isspeptin, a hypothalamic neuropeptide derived from the KISS1/Kiss1, with the ability to activate the kisspeptin receptor (Kiss-R), has proven to play a key role in vertebrate reproduction (1). Kisspeptin neurons are present in the hypothalamic region, but their neural targets are not restricted to the hypothalamic region (2, 3). Furthermore, recent studies in mammals have revealed the expression of Kiss1 in several brain regions, including the medial amygdala (4). However, the knowledge of the potential role of kisspeptin-Kiss-R in nonhypothalamic regions remains limited. Using the teleost fish, we have previously identified two homologous genes (kiss1 and kiss2) encoding kisspeptin (5), of which kiss1 is a conserved ortholog of mammalian KISS1/Kiss1, whereas kiss2 has been found in hypothalamic nuclei of only nonmammalian vertebrates, which include amphibians and teleosts (6). In the zebrafish, kiss1 and kissr1 mRNAs are predominantly expressed in the ventral habenula (vHb) (5, 7). In nonmammalian vertebrates, the dorsal habenula (dHb) and the vHb are homologous to the medial (mHb) and lateral (lHb) habenula in mammals (8, 9). The lHb in primates regulates punishment avoidance behavior (10) and in rodents, it controls anxiety and fear (11), which suggests that nonmammalian vHb, homologous to the mammalian lHb, could modulate fear response. Furthermore, the vHb projects Kiss1 neuronal fibers to the median raphe (MR) (7, 12), a site adjacent to serotonergic (5-hydroxytrypt...

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“…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.…”

Section: (A) Conditioned Swimming Behavioursmentioning

confidence: 99%

Zebrafish forebrain and temporal conditioning

Cheng

Jesuthasan

Penney

2014

Phil. Trans. R. Soc. B

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The rise of zebrafish as a neuroscience research model organism, in conjunction with recent progress in single-cell resolution whole-brain imaging of larval zebrafish, opens a new window of opportunity for research on interval timing. In this article, we review zebrafish neuroanatomy and neuromodulatory systems, with particular focus on identifying homologies between the zebrafish forebrain and the mammalian forebrain. The neuroanatomical and neurochemical basis of interval timing is summarized with emphasis on the potential of using zebrafish to reveal the neural circuits for interval timing. The behavioural repertoire of larval zebrafish is reviewed and we demonstrate that larval zebrafish are capable of expecting a stimulus at a precise time point with minimal training. In conclusion, we propose that interval timing research using zebrafish and whole-brain calcium imaging at single-cell resolution will contribute to our understanding of how timing and time perception originate in the vertebrate brain from the level of single cells to circuits.

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The habenula is crucial for experience-dependent modification of fear responses in zebrafish

Cited by 346 publications

References 15 publications

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

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

Habenular kisspeptin modulates fear in the zebrafish

Zebrafish forebrain and temporal conditioning

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