ZFIN ID: ZDB-LAB-991015-4
Jesuthasan Lab
PI/Director: Jesuthasan, Suresh
Contact Person: Jesuthasan, Suresh
Email: sureshj@ntu.edu.sg
URL: http://sureshj7.wixsite.com/website
Address: 04-13B Proteos Biopolis Drive Singapore 138673
Country: Singapore
Phone: 65-6586-9545
Line Designation: lkc

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Brain State and Behavior
An animal’s survival depends on its ability to react appropriately to environmental stimuli. The responses can be innate, but can also be modified by experience and internal state (e.g. hunger and time of day). The goal of the lab is to gain insight into how the vertebrate brain generates an optimal response. To do this, we use a combination of anatomy, high-resolution functional imaging, genetics, behavioral assays and modelling. Behavior is generated by neural circuits. Connectivity between circuit components is not fixed, but is dynamically regulated by neuromodulators. The major question they are interested in, thus, is how neuromodulator release is controlled based on sensory stimuli and internal states.

The Alarm Response
A starting point for experiments is the alarm response. In the 1930’s Karl von Frisch noticed that injury to a European minnow caused a fright reaction in other members of the fish school. He demonstrated that the skin contains substances, termed Schreckstoff, which act via the olfactory system to trigger a state of fear. The fish change their swimming behaviour dramatically - either darting or freezing - in response to this alarm pheromone. Subsequent experiments by other scientists established that many freshwater fish species have this response. All the classical hallmarks of fear, including physiological changes such as increase in blood cortisol levels, can be triggered by Schreckstoff. Current experiments are focused on understanding the biology underlying the alarm response, including the mechanism by which the alarm substance is generated and the neural circuits regulating the behaviour.

The habenula
The habenula is an evolutionarily conserved structure that regulates neuromodulator release. It is well placed to control functional connectivity in response to a wide range of variables, as it receives input from all sensory systems, including the olfactory and visual systems, and receives reward information from the basal ganglia. Information from the circadian clock is also channelled to the habenula. The lab uses a combination of imaging and manipulation to investigate how information is processed in the habenula to enable rapid selection of optimal behaviour.


Basnakova, A., Cheng, R.K., Chia, J.S.M., D'Agostino, G., Suryadi, ., Tan, G.J.H., Langley, S.R., Jesuthasan, S. (2021) The habenula clock influences response to a stressor. Neurobiology of stress. 15:100403
Cheung, K.Y., Jesuthasan, S.J., Baxendale, S., van Hateren, N.J., Marzo, M., Hill, C.J., Whitfield, T.T. (2021) Olfactory Rod Cells: A Rare Cell Type in the Larval Zebrafish Olfactory Epithelium With a Large Actin-Rich Apical Projection. Frontiers in Physiology. 12:626080
Jesuthasan, S., Krishnan, S., Cheng, R.K., Mathuru, A. (2020) Neural correlates of state transitions elicited by a chemosensory danger cue. Progress in neuro-psychopharmacology & biological psychiatry. 111:110110
Ramaswamy, M., Cheng, R.K., Jesuthasan, S. (2020) Identification of GABAergic neurons innervating the zebrafish lateral habenula. The European journal of neuroscience. 52(8):3918-3928
Zhang, S., Reljić, B., Liang, C., Kerouanton, B., Francisco, J.C., Peh, J.H., Mary, C., Jagannathan, N.S., Olexiouk, V., Tang, C., Fidelito, G., Nama, S., Cheng, R.K., Wee, C.L., Wang, L.C., Duek Roggli, P., Sampath, P., Lane, L., Petretto, E., Sobota, R.M., Jesuthasan, S., Tucker-Kellogg, L., Reversade, B., Menschaert, G., Sun, L., Stroud, D.A., Ho, L. (2020) Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly. Nature communications. 11:1312
Chia, J.S.M., Wall, E.S., Wee, C.L., Rowland, T.A.J., Cheng, R.K., Cheow, K., Guillemin, K., Jesuthasan, S. (2019) Bacteria evoke alarm behaviour in zebrafish. Nature communications. 10:3831
Jesuthasan, S. (2018) The vertebrate habenula. Seminars in cell & developmental biology. 78:102
Jesuthasan, S. (2018) The thalamo-habenula projection revisited. Seminars in cell & developmental biology. 78:116-119
Mohamed, G.A., Cheng, R.K., Ho, J., Krishnan, S., Mohammad, F., Claridge-Chang, A., Jesuthasan, S. (2017) Optical inhibition of larval zebrafish behaviour with anion channelrhodopsins. BMC Biology. 15:103
Cheng, R.K., Krishnan, S., Lin, Q., Kibat, C., Jesuthasan, S. (2017) Characterization of a thalamic nucleus mediating habenula responses to changes in ambient illumination. BMC Biology. 15:104
Lin, Q., Jesuthasan, S. (2017) Masking of a circadian behavior in larval zebrafish involves the thalamo-habenula pathway. Scientific Reports. 7:4104
Lupton, 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)
Kibat, C., Krishnan, S., Ramaswamy, M., Baker, B.J., Jesuthasan, S. (2016) Imaging voltage in zebrafish as a route to characterizing a vertebrate functional connectome: promises and pitfalls of genetically encoded indicators. Journal of neurogenetics. 30:80-8
Cheng, R.K., Krishnan, S., Jesuthasan, S. (2016) Activation and inhibition of tph2 serotonergic neurons operate in tandem to influence larval zebrafish preference for light over darkness. Scientific Reports. 6:20788
Krishnan, S., Mathuru, A.S., Kibat, C., Rahman, M., Lupton, C.E., Stewart, J., Claridge-Chang, A., Yen, S.C., Jesuthasan, S. (2014) The Right Dorsal Habenula Limits Attraction to an Odor in Zebrafish. Current biology : CB. 24(11):1167-75
Cheng, R.K., Jesuthasan, S.J., and Penney, T.B. (2014) Zebrafish forebrain and temporal conditioning. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 369(1637):20120462
Schirmer, A., Jesuthasan, S., and Mathuru, A.S. (2013) Tactile stimulation reduces fear in fish. Frontiers in behavioral neuroscience. 7:167
Tan, S.J., Kee, M.Z., Mathuru, A.S., Burkholder, W.F., and Jesuthasan, S.J. (2013) A microfluidic device to sort cells based on dynamic response to a stimulus. PLoS One. 8(11):e78261
Mathuru, A.S., and Jesuthasan, S. (2013) The medial habenula as a regulator of anxiety in adult zebrafish. Frontiers in neural circuits. 7:99
Mathuru, A.S., Kibat, C., Cheong, W.F., Shui, G., Wenk, M.R., Friedrich, R.W., and Jesuthasan, S. (2012) Chondroitin fragments are odorants that trigger fear behavior in fish. Current biology : CB. 22(6):538-544
Jesuthasan, S. (2012) Fear, anxiety, and control in the zebrafish. Developmental Neurobiology. 72(3):395-403
Kalueff, A.V., Stewart, A.M., Kyzar, E.J., Cachat, J., Gebhardt, M., Landsman, S., Robinson, K., Maximino, C., Herculano, A.M., Jesuthasan, S., Wisenden, B., Bally-Cuif, L., Lange, M., Vernier, P., Norton, W., Tierney, K., Tropepe, V., and Neuhauss, S. (2012) Time to recognize zebrafish ‘affective’ behavior. Behaviour. 149:1019-1036
Cheng, R.K., Jesuthasan, S., and Penney, T.B. (2011) Time for zebrafish. Frontiers in Integrative Neuroscience. 5:40
Lee, A., Mathuru, A.S., Teh, C., Kibat, C., Korzh, V., Penney, T.B., and Jesuthasan, S. (2010) The habenula prevents helpless behavior in larval zebrafish. Current biology : CB. 20(24):2211-2216
Sheng, D., Qu, D., Kwok, K.H., Ng, S.S., Lim, A.Y., Aw, S.S., Lee, C.W., Sung, W.K., Tan, E.K., Lufkin, T., Jesuthasan, S., Sinnakaruppan, M., and Liu, J. (2010) Deletion of the WD40 domain of LRRK2 in Zebrafish causes Parkinsonism-like loss of neurons and locomotive defect. PLoS Genetics. 6(4):e1000914
Hendricks, M., and Jesuthasan, S. (2009) PHR regulates growth cone pausing at intermediate targets through microtubule disassembly. The Journal of neuroscience : the official journal of the Society for Neuroscience. 29(20):6593-6598
Hendricks, M., Mathuru, A.S., Wang, H., Silander, O., Kee, M.Z., and Jesuthasan, S. (2008) Disruption of Esrom and Ryk identifies the roof plate boundary as an intermediate target for commissure formation. Molecular and cellular neurosciences. 37(2):271-283
Jesuthasan, S.J., and Mathuru, A.S. (2008) The alarm response in zebrafish: innate fear in a vertebrate genetic model. Journal of neurogenetics. 22(3):211-228
Hendricks, M., and Jesuthasan, S. (2007) Asymmetric innervation of the habenula in zebrafish. The Journal of comparative neurology. 502(4):611-619
Hendricks, M., and Jesuthasan, S. (2007) Electroporation-based methods for in vivo, whole mount and primary culture analysis of zebrafish brain development. Neural Development. 2(1):6
Etard, C., Behra, M., Ertzer, R., Fischer, N., Jesuthasan, S., Blader, P., Geisler, R., and Strähle, U. (2005) Mutation in the delta-subunit of the nAChR suppresses the muscle defects caused by lack of Dystrophin. Developmental dynamics : an official publication of the American Association of Anatomists. 234(4):1016-1025
Feng, B., Bulchand, S., Yaksi, E., Friedrich, R.W., and Jesuthasan, S.J. (2005) The recombination activation gene 1 (Rag1) is expressed in a subset of zebrafish olfactory neurons but is not essential for axon targeting or amino acid detection. BMC Neuroscience. 6:46
Le Guyader, S., Maier, J., and Jesuthasan, S. (2005) Esrom, an ortholog of PAM (protein associated with c-myc), regulates pteridine synthesis in the zebrafish. Developmental Biology. 277(2):378-386
D'Souza, J., Hendricks, M., Le Guyader, S., Subburaju, S., Grunewald, B., Scholich, K., and Jesuthasan, S. (2005) Formation of the retinotectal projection requires Esrom, an ortholog of PAM (protein associated with Myc). Development (Cambridge, England). 132(2):247-256
Hendricks, M., and Jesuthasan, S. (2004) Form and Function in the Zebrafish Nervous System. In Fish Development and Genetics - the Zebrafish and Medaka Models. Gong, Z. and Korh, V., Eds. Book series of "Molecular Aspects of Fish and Marine Biology". 2
Wagle, M., Grunewald, B., Subburaju, S., Barzaghi, C., Le Guyader, S., Chan, J., and Jesuthasan, S. (2004) EphrinB2a in the zebrafish retinotectal system. Journal of neurobiology. 59(1):57-65
Wagle, M. and Jesuthasan, S. (2003) Baculovirus-mediated gene expression in zebrafish. Marine biotechnology (New York, N.Y.). 5(1):58-63
Feng, B., Schwarz, H., and Jesuthasan, S. (2002) Furrow-specific endocytosis during cytokinesis of zebrafish blastomeres. Experimental cell research. 279(1):14-20
Jesuthasan, S. (2002) Genetics and development: zebrafish in the spotlight. Science (New York, N.Y.). 297(5586):1484-1485
Jesuthasan, S. and Subburaju, S. (2002) Gene transfer into zebrafish by sperm nuclear transplantation. Developmental Biology. 242(2):88-95
Le Guyader, S. and Jesuthasan, S. (2002) Analysis of xanthophore and pterinosome biogenesis in zebrafish using methylene blue and pteridine autofluorescence. Pigment cell research. 15(1):27-31
Jesuthasan, S. (1998) Furrow-associated microtubule arrays are required for the cohesion of zebrafish blastomeres following cytokinesis. Journal of Cell Science. 111:3695-3703
Jesuthasan, S. (1997) Neural crest cell migration in the zebrafish can be mimicked by inert objects: mechanism and implication of latex bead movement in embryos. The Journal of experimental zoology. 277(6):425-434
Strähle, U., Jesuthasan, S., Blader, P., Garcia-Villalba, P., Hatta, K., and Ingham, P.W. (1997) one-eyed pinhead is required for development of the ventral midline of the zebrafish (Danio rerio) neural tube. Genes and function. 1:131-148
Jesuthasan, S. and Strähle, U. (1997) Dynamic microtubules and specification of the zebrafish embryonic axis. Current biology : CB. 7(1):31-42
Jesuthasan, S. (1996) Contact inhibition collapse and pathfinding of neural crest cells in the zebrafish trunk. Development (Cambridge, England). 122:381-389
Strähle, U., and Jesuthasan, S. (1993) Ultraviolet irradiation impairs epiboly in zebrafish embryos: evidence for a microtubule-dependent mechanism of epiboly. Development (Cambridge, England). 119:909-919