ZFIN ID: ZDB-LAB-991015-4
STATEMENT OF RESEARCH INTERESTS
GENOMIC FEATURES ORIGINATING FROM THIS LAB
all 18 genomic features
Brain State and Behavior
ZEBRAFISH PUBLICATIONS OF LAB MEMBERS
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 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.
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
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)
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
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
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
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., 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
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
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
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
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