Abstract
The habenula is a phylogenetically conserved epithalamic structure, which conveys negative information via inhibition of mesolimbic dopamine neurons. We have previously shown the expression of kisspeptin (Kiss1) in the habenula and its role in the modulation of fear responses in the zebrafish. In this study, to investigate whether habenular Kiss1 regulates fear responses via dopamine neurons in the zebrafish, Kiss1 peptides were intracranially administered close to the habenula, and the expression of dopamine-related genes (th1, th2 and dat) were examined in the brain using real-time PCR and dopamine levels using LC–MS/MS. th1 mRNA levels and dopamine levels were significantly increased in the telencephalon 24-h and 30-min after Kiss1 administration, respectively. In fish administered with Kiss1, expression of neural activity marker gene, npas4a and kiss1 gene were significantly decreased in the ventral habenula. Application of neural tracer into the median raphe, site of habenular Kiss1 neural terminal projections showed tracer-labelled projections in the medial forebrain bundle towards the telencephalon where dopamine neurons reside. These results suggest that Kiss1 negatively regulates its own neuronal activity in the ventral habenula via autocrine action. This, in turn affects neurons of the median raphe via interneurons, which project to the telencephalic dopaminergic neurons.
Highlights
The habenula is a phylogenetically conserved epithalamic structure, which conveys negative information via inhibition of mesolimbic dopamine neurons
The habenula is divided into the dorsal and the ventral habenula[1], which send efferent outputs to different targets[2]
Central administration of Kiss[1] peptides at dose of 10–12 mol/fish significantly (P < 0.05 or P < 0.0001) upregulated expression levels for th[1], th2 and dat mRNAs in the whole brain of fishes only 24-h after administration (Fig. 1C–E) but not 30-min, 1-h, 3-h or 6-h after administration as compared with those of control fishes, except for small decrease in th[1] mRNA levels in the group treated with 1 0–12 mol/fish of Kiss[1] at 3-h post administration (Fig. 1C). th[1] expression was increased at 24-h when the fish were treated with Kiss1 10–9 mol/fish (P < 0.05) (Fig. 1C)
Summary
The habenula is a phylogenetically conserved epithalamic structure, which conveys negative information via inhibition of mesolimbic dopamine neurons. To investigate whether habenular Kiss[1] regulates fear responses via dopamine neurons in the zebrafish, Kiss[1] peptides were intracranially administered close to the habenula, and the expression of dopamine-related genes (th[1], th and dat) were examined in the brain using real-time PCR and dopamine levels using LC–MS/MS. Application of neural tracer into the median raphe, site of habenular Kiss[1] neural terminal projections showed tracer-labelled projections in the medial forebrain bundle towards the telencephalon where dopamine neurons reside. These results suggest that Kiss[1] negatively regulates its own neuronal activity in the ventral habenula via autocrine action. To examine the potential association between habenular Kiss[1] neurons and dopaminergic neuronal population, we applied neural tracer in the MR, site of Kiss[1] terminal projections
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