Recent human motor learning studies revealed that punishment seemingly accelerated motor learning but reward enhanced consolidation of motor memory. It is not evident how intrinsic properties of ...reward and punishment modulate the potentially dissociable effects of reward and punishment on motor learning and motor memory. It is also not clear what causes the dissociation of the effects of reward and punishment. By manipulating probability of distribution, a critical property of reward and punishment, the present study demonstrated that probability had distinct modulation on the effects of reward and punishment in adapting to a sudden visual rotation and consolidation of the adaptation memory. Specifically, two probabilities of monetary reward and punishment distribution, 50 and 100%, were applied during young adult participants adapting to a sudden visual rotation. Punishment and reward showed distinct effects on motor adaptation and motor memory. The group that received punishments in 100% of the adaptation trials adapted significantly faster than the other three groups, but the group that received rewards in 100% of the adaptation trials showed marked savings in re-adapting to the same rotation. In addition, the group that received punishments in 50% of the adaptation trials that were randomly selected also had savings in re-adapting to the same rotation. Sensitivity to sensory prediction error or difference in explicit process induced by reward and punishment may likely contribute to the distinct effects of reward and punishment.
Visuomotor adaptation involves multiple processes such as explicit learning, implicit learning from sensory prediction errors, and model-free mechanisms like use-dependent plasticity. Recent findings ...show that reward and punishment differently affect visuomotor adaptation. This study examined whether punishment and reward had distinct effects on explicit learning. When participants practised adapting to a large, abrupt visual rotation during reaching for a virtual visual target, visual feedback of the cursor was not provided. Only performance-based scalar reward or punishment feedback (money gained or lost) was used, thereby emphasising explicit processes during adaptation. The results revealed that punishment, compared with reward, induced faster adaptation and greater variability of reaching in the initial phase of adaptation. We interpret these findings as reflecting enhanced explicit learning, likely due to loss aversion.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
•Tg(gnih:mCherry) zebrafish shows GnIH cells restricted in the NPPv regions.•GnIH processes project to the hypothalamus, telencephalon, and olfactory bulb.•GnIH processes are in contact with the ...TN-GnRH3 cell somata in the olfactory bulb.•Hypothalamic GnIH processes make a close apposition with the GnRH3 fibers.•GnIH-3 peptide injection stimulates gnrh3 expression in the zebrafish brain.
Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotropin secretion in birds and mammals. However, the role of GnIH (Lpxrfa) in teleosts is unknown. In this study, a transgenic zebrafish (Danio rerio) line Tg(gnih:mCherry) was developed to determine the organization of GnIH neurons in the brain. Another transgenic line, Tg(gnih:mCherry; gnrh3:eGFP), was established to determine the positional relationships between GnIH and GnRH3 neurons. In these transgenic lines, the mCherry protein was specifically expressed in GnIH neurons, and eGFP was expressed exclusively in GnRH3 neurons. We found that GnIH cell somata were restricted to the posterior periventricular nucleus (NPPv). Most GnIH neuronal processes projected to the hypothalamus, but a few extended to the posterior tuberculum, telencephalon, and olfactory bulb. GnIH neuronal processes were in close apposition with GnRH3 cell somata and processes in the preoptic-hypothalamic area but were seldom in direct contact. However, in the olfactory bulb, GnIH neuronal processes were in proximity to the terminal nerve GnRH3 cell somata. Neither GnIH cell soma nor neuronal processes were detected in the pituitary, although GnIH receptor mRNAs (npffr1l1, npffr1l2, and npffr1l3) were detected. Intraperitoneal administration of GnIH-3 peptides promoted the transcription of brain gnrh3 as well as pituitary fshβ but not lhβ. Thus, GnIH cell somata were specifically distributed in the NPPv, and their fibers extended to the hypothalamus and advanced to the telencephalon and olfactory bulb. We conclude that GnIH may directly stimulate terminal nerve GnRH3 neurons in the zebrafish brain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The rice field eel (Monopterus albus) is a protogynous hermaphroditic fish reared commercially as an aquaculture species in East Asia. Artificial breeding of rice field eels requires an abundance of ...adult females and males; however, the eels need to undergo a long period of female and intersexual stages before they develop into males, which results in a shortage of functional males in production practice. This study developed an artificial method for producing functional males through the oral administration of an aromatase inhibitor (AI, letrozole: 300 mg/kg feed) in juvenile fish. Histological analysis of gonadal sections of treated fish revealed the transition of primary ovaries to mature testes. During the initial period of the AI treatment, 2-month-old rice field eels were exclusively female. AI administration resulted in a significant reduction in 17β-estradiol levels and increase in testosterone and 11-ketotestosterone levels in vivo. Cell proliferation occurred in the outer layer of the gonadal epithelium, and oocytes degenerated in the ovaries. After 120 days of AI treatment, the ovaries were completely converted to testes. The sexually reversed fish maintained the male sex and produced functional sperm after cessation of drug treatment. Notably, artificially sex-reversed males' fecundity did not differ significantly from wild-type males. Quantitative PCR analysis revealed that the expression of cyp19a1a decreased, whereas the mRNA levels of estrogen receptors esr1, esr2a, and esr2b increased significantly during AI treatment. Moreover, the expression of foxl2 was downregulated, whereas dmrt1, amh, and sox9 were upregulated in the gonads of fish administered AI. This study revealed that endogenous estrogen synthesis plays a key role in the sex change of rice field eels, with ovaries undergoing a reversal to testes in response to estrogen insufficiency. Such artificially induced sex conversion will be of considerable value in breeding rice field eels.
•Estradiol plays a key role in sex change of protogynous rice field eel.•Aromatase inhibitor treatment induces female to male sex reversal in juvenile rice field eel.•The aromatase inhibitor induced males had the equivalent fecundity with the wild males.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Kisspeptin2 is a neuropeptide widely found in the brain and multiple peripheral tissues in the zebrafish. The pituitary is the center of synthesis and secretes various endocrine hormones. However, ...Kiss2 innervation in the zebrafish pituitary is unknown. In this study, the organization of Kiss2 cells and structures in the zebrafish pituitary by promoter-driving mCherry-labeling Kiss2 neurons were investigated. Kiss2 neurons in the hypothalamus do not project into the pituitary. Kiss2 cells are found in the female pituitary. Unidentified Kiss2 cells and extensions are located in the proximal pars distalis (PPD), similar to the distribution of Gnrh3 fibers. Kiss2 structures reside alongside Gnrh3 fibers. No Kiss2 structures are found in the male pituitary. The transcriptional expression of the kisspeptin receptor kiss1rb is detected in both female and male pituitaries. In situ hybridization shows that kiss1rb-positive cells are located in the PPD and pars intermedia (PI). In vitro Kiss2-10 treatment stimulates Akt and Erk phosphorylation and significantly induces lhβ, fshβ, and prl1 mRNA expression in the female pituitary. The results in this study suggest that Kiss2 and Kiss1rb may form an independent paracrine or autocrine system in the female zebrafish pituitary. Kiss2 and Kiss1rb signaling regulates the expression of pituitary hormones.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Folliculogenesis is controlled by intimate communications between oocytes and surrounding follicle cells. Epidermal growth factor (EGF/Egf) is an important paracrine/autocrine factor in vertebrate ...ovary, and it is well known for its stimulation of oocyte maturation. However, the role of EGF signaling through its receptor (EGFR/Egfr) in ovarian folliculogenesis is poorly understood, especially at early stages of follicle development. In this study, we created zebrafish mutants for Egf (
) and Egfr (
and
) by CRISPR/Cas9 technique. Surprisingly, these mutants all survived well with little abnormality in growth and development. Spermatogenesis and folliculogenesis were both normal in
males and females. Their fecundity was comparable to that of the wildtype fish at 4 months post-fertilization (mpf); however, the fertilization rate of mutant eggs (
) decreased significantly at 7 mpf. Interestingly, disruption of
(
) led to failed follicle activation with folliculogenesis being blocked at primary-secondary growth transition (PG-SG transition), leading to female infertility, whereas the mutant males remained fertile. The mutant ovary (
) showed abnormal expression of a substantial number of genes involved in oxidative metabolism, gene transcription, cytomembrane transport, steroid hormone biosynthesis, and immune response. The stunted PG oocytes in
ovary eventually underwent degeneration after 6 months followed by sex reversal to males with functional testes. No abnormal phenotypes were found in the mutant of truncated form of EGFR (
). In summary, our data revealed critical roles for EGFR signaling in early folliculogenesis, especially at the PG-SG transition or follicle activation.
Abstract
Gonadotropin-releasing hormone (Gnrh) plays important roles in reproduction by stimulating luteinizing hormone release, and subsequently ovulation and sperm release, ultimately controlling ...reproduction in many species. Here we report on a new role for this decapeptide. Surprisingly, Gnrh3-null zebrafish generated by CRISPR/Cas9 exhibited a male-biased sex ratio. After the dome stage, the number of primordial germ cells (PGCs) in gnrh3-/- fish was lower than that in wild-type, an effect that was partially rescued by gnrh3 overexpression. A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis revealed no detectable apoptosis of PGCs in gnrh3-/- embryos. Proliferating PGCs could be detected in wild-type embryos, while there was no detectable signal in gnrh3-/- embryos. Compared with wild type, the phosphorylation of AKT was not significantly different in gnrh3-/- embryos, but the phosphorylation of ERK1/2 decreased significantly. Treatment with a Gnrh analog (Alarelin) induced ERK1/2 phosphorylation and increased PGC numbers in both wild-type and gnrh3-/- embryos, and this was blocked by the MEK inhibitor PD0325901. The relative expression of sox9a, amh, and cyp11b were significantly upregulated, while cyp19a1a was significantly downregulated at 18 days post-fertilization in gnrh3-/- zebrafish. Taken together, these results indicate that Gnrh3 plays an important role in early sex differentiation by regulating the proliferation of PGCs through a MAPK-dependent path.
Primordial germ cells (PGCs) play an important role in sexual fate determination and gonadal development in gonochoristic fish, such as zebrafish and medaka. However, little is known about the ...function of PGCs in hermaphroditic fish. Rice field eel (
Monopterus albus
), a protogynous hermaphroditic fish, is an economically valuable aquaculture species. We eliminated PGCs in rice field eels during embryogenesis via morpholino-mediated knockdown
dead end
(
dnd
). The PGCs-depleted gonads developed into testis-like structures with Sertoli cells and Leydig cells. The gene expression pattern of 15-month-old PGCs-depleted gonads showed that male-biased genes,
dmrt1
,
sox9a
,
gsdf
, and
amh
, were significantly higher than that of the WT, whereas female-biased genes,
foxl2
and
cyp19a1a
, were significantly decreased. These results indicate that PGCs are essential for ovarian differentiation in rice field eel, and PGCs-depleted gonads develop into sterile males without undergoing the female and intersex stages. Our study is the first to identify the role of PGCs in sex differentiation in rice field eel, a protogynous hermaphrodite teleost. And it is of great significance in rice field eel for discovering the underlying mechanism of sex differentiation and establishing sex control technology.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The greater amberjack (Seriola dumerili), a pelagic marine species with a global distribution, has considerable worldwide potential as an aquaculture species. However, difficulties have been ...encountered in inducing spontaneous spawning in cultured fish stocks. In this study, we analysed the key regulatory factors, secretoneurin (SN) and gonadotropin-releasing hormone (GnRH), in greater amberjack. Active peptides of SN and GnRH, SdSNa, and SdGnRH, respectively, were obtained by comparative analysis of homologous proteins from different species. Amino acid substitutions of the SdGnRH decapeptide at position 6 with a dextrorotatory (D) amino acid and at position 10 with an ethylamide group yielded a super-active agonist (SdGnRHa). The injection of SdSNa and SdGnRHa elevated luteinizing hormone, thyroid-stimulating hormone, and oxytocin levels in the sera of sexually mature fish, whereas it reduced the level of follicle-stimulating hormone. Furthermore, in response to the SdSNa and SdGnRHa injections, we detected an increase in the expression of genes associated with oocyte development and spermatogenesis. We established that the greater amberjack cultured along the southern coast of China reached sexual maturity at three years of age, and its reproductive season extended from February to April. Spawning of the cultured greater amberjack was successfully induced with a single injection of SdGnRHa/SdSN/DOM/HCG. Our findings indicate that similar to GnRHa, SNa is a potential stimulator of reproduction that can be used to artificially induce spawning in marine fish.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Epilepsy surgery is the most effective therapeutic approach for children with drug resistant epilepsy (DRE). Recent advances in neurosurgery, such as the Laser Interstitial Thermal Therapy (LITT), ...improved the safety and non-invasiveness of this method. Electric and magnetic source imaging (ESI/MSI) plays critical role in the delineation of the epileptogenic focus during the presurgical evaluation of children with DRE. Yet, they are currently underutilized even in tertiary epilepsy centers. Here, we present a case of an adolescent who suffered from DRE for 16 years and underwent surgery at Cook Children's Medical Center (CCMC). The patient was previously evaluated in a level 4 epilepsy center and treated with multiple antiseizure medications for several years. Presurgical evaluation at CCMC included long-term video electroencephalography (EEG), magnetoencephalography (MEG) with simultaneous conventional EEG (19 channels) and high-density EEG (256 channels) in two consecutive sessions, MRI, and fluorodeoxyglucose - positron emission tomography (FDG-PET). Video long-term EEG captured nine focal-onset clinical seizures with a maximal evolution over the right frontal/frontal midline areas. MRI was initially interpreted as non-lesional. FDG-PET revealed a small region of hypometabolism at the anterior right superior temporal gyrus. ESI and MSI performed with dipole clustering showed a tight cluster of dipoles in the right anterior insula. The patient underwent intracranial EEG which indicated the right anterior insular as seizure onset zone. Eventually LITT rendered the patient seizure free (Engel 1; 12 months after surgery). Retrospective analysis of ESI and MSI clustered dipoles found a mean distance of dipoles from the ablated volume ranging from 10 to 25 mm. Our findings highlight the importance of recent technological advances in the presurgical evaluation and surgical treatment of children with DRE, and the underutilization of epilepsy surgery in children with DRE.