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dc.contributor.authorLupton, Charlotteen
dc.contributor.authorSengupta, Mohinien
dc.contributor.authorCheng, Ruey-Kuangen
dc.contributor.authorChia, Joanneen
dc.contributor.authorThirumalai, Vatsalaen
dc.contributor.authorJesuthasan, Sureshen
dc.identifier.citationLupton, C., Sengupta, M., Cheng, R.-K., Chia, J., Thirumalai, V., & Jesuthasan, S. (2017). Loss of the habenula intrinsic neuromodulator Kisspeptin1 affects learning in larval zebrafish. eNeuro, 4(3), e0326-16.2017-. doi:10.1523/ENEURO.0326-16.2017en
dc.description.abstractLearning how to actively avoid a predictable threat involves two steps: recognizing the cue that predicts upcoming punishment and learning a behavioral response that will lead to avoidance. In zebrafish, ventral habenula (vHb) neurons have been proposed to participate in both steps by encoding the expected aversiveness of a stimulus. vHb neurons increase their firing rate as expectation of punishment grows but reduce their activity as avoidance learning occurs. This leads to changes in the activity of raphe neurons, which are downstream of the vHb, during learning. How vHb activity is regulated is not known. Here, we ask whether the neuromodulator Kisspeptin1, which is expressed in the ventral habenula together with its receptor, could be involved. Kiss1 mutants were generated with CRISPR/Cas9 using guide RNAs targeted to the signal sequence. Mutants, which have a stop codon upstream of the active Kisspeptin1 peptide, have a deficiency in learning to avoid a shock that is predicted by light. Electrophysiology indicates that Kisspeptin1 has a concentration-dependent effect on vHb neurons: depolarizing at low concentrations and hyperpolarizing at high concentrations. Two-photon calcium imaging shows that mutants have reduced raphe response to shock. These data are consistent with the hypothesis that Kisspeptin1 modulates habenula neurons as the fish learns to cope with a threat. Learning a behavioral strategy to overcome a stressor may thus be accompanied by physiological change in the habenula, mediated by intrinsic neuromodulation.en
dc.description.sponsorshipASTAR (Agency for Sci., Tech. and Research, S’pore)en
dc.description.sponsorshipMOE (Min. of Education, S’pore)en
dc.format.extent9 p.en
dc.rights© 2017 Lupton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.en
dc.subjectCalcium Imagingen
dc.titleLoss of the habenula intrinsic neuromodulator Kisspeptin1 affects learning in larval zebrafishen
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en
dc.description.versionPublished versionen
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