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The serotonergic neurons in the raphe nucleus are implicated in various cognitive functions such as learning and emotion. In vertebrates, the raphe nucleus is divided into the dorsal raphe and the median raphe. In contrast to the abundance of knowledge on the functions of the dorsal raphe, the roles of the serotonergic neurons in the median raphe are relatively unknown. The studies using zebrafish revealed that the median raphe serotonergic neurons receive input from the two distinct pathways from the habenula and the IPN. The use of zebrafish may reveal the function of the Hb-IPN-median raphe pathway. To clarify the functions of the median raphe serotonergic neurons, it is necessary to distinguish them from those in the dorsal raphe. Most median raphe serotonergic neurons originate from rhombomere 2 in mice, and we generated the transgenic zebrafish which can label the serotonergic neurons derived from rhombomere 2. In this study, we found the serotonergic neurons derived from rhombomere 2 are localized in the median raphe and project axons to the rostral dorsal pallium in zebrafish. This study suggests that this transgenic system has the potential to specifically reveal the function and information processing of the Hb-IPN-raphe-telencephalon circuit in learning., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Social subordination, which causes severe stress in animals, can affect animal's behaviors, homeostasis, and mental health. In rodents, experiences of repeated social defeats, but not a single defeat, induce a depression-like state. However, it is unclear whether such experiences similarly affect behaviors of other model animals than rodents. Here, we established a behavioral paradigm for repeated social defeats with zebrafish, an emerging model for behavioral neuroscience and pharmacological analysis. We put fish into repeated social subordination for 6 consecutive days. Using behaviors during fighting as indicators, we observed that experiencing repeated social defeats led to a reduction in fight frequency and duration. The continuously-defeated zebrafish failed to win even against the transgenic fish with an impaired winning-associated neural pathway. These results suggest that repeated social defeats led to demotivation to fight and to win against opponents. Moreover, they showed strong activity in the ventral habenula, an evolutionary homolog of the mammalian lateral habenula. However, unlike the mice model, the continuously-defeated zebrafish showed no change in anxiety level and sociability. Our established behavioral paradigm will be a new tool to investigate neural mechanisms underlying social defeats., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Many animals fight for dominance between conspecifics. Because winners could obtain more resources than losers, fighting outcomes are important for the animal's survival, especially in a situation with insufficient resources, such as hunger. However, it remains unclear whether and how hunger affects fighting outcomes. Herein, we investigate the effects of food deprivation on brain activity and fighting behaviors in zebrafish. We report that starvation induces winning in social conflicts. Before the fights, starved fish show potentiation of the lateral subregion of the dorsal habenula (dHbL)-dorsal/intermediate interpeduncular nucleus (d/iIPN) pathway, which is known to be essential for and potentiated after winning fights. Circuit potentiation is mediated by hypothalamic orexin/hypocretin neuropeptides, which prolong AMPA-type glutamate receptor (AMPAR) activity by increasing the expression of a flip type of alternative splicing variant of the AMPAR subunit. This mechanism may underlie how hungry vertebrates win fights and may be commonly shared across animal phylogeny. • A 6-day starvation makes zebrafish win in social conflict • Starvation causes potentiation of the winner pathway from the habenula to the IPN • Starvation-induced orexin signal biases splicing of the AMPAR gene in the IPN • Activity of the AMPAR splice variant is prolonged, driving synaptic potentiation in the IPN Nakajo et al. show that 6-day starvation potentiates the winner-associated dHbL-d/iIPN pathway by prolonging AMPAR activity in the dIPN region through increasing the expression level of an alternative splicing variant of AMPAR subunits, gria3b-flip. These neuromodulations in the dIPN are induced by the orexin/hypocretin signal that is activated in a starved state. [ABSTRACT FROM AUTHOR]