Jesuthasan, Suresh

Research Interests:

Fear and anxiety in the zebrafish

The Neural Circuitry and Behavior lab is interested in understanding emotion. We currently focus on fear and anxiety, and are investigating questions such as how the brain computes the appropriate response for a given threat. We examine feedback mechanisms that regulate the level of fear, and are also interested in how the duration of a state of anxiety is determined.

All experiments are conducted using the zebrafish. In addition to allowing genetic analysis, neural activity can be imaged at high resolution in the intact animal. Transgenic lines also enable the manipulation of specific cells.

The lab uses two behavioral paradigms. The first, a robust example of innate fear, is the alarm response, while the second is classical conditioning.

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 behavior 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.

We have used classical biochemical separation and mass spectrometry to identify the alarm substance. Calcium imaging of the brain has enabled identification of regions that are activated following detection of the alarm substance. In addition, we have isolated a number of mutant lines which show an abnormal alarm response.

Conditioning

An influential idea in psychology is that the degree of control an animal has over its environment can affect behavior in a very profound way. Animals that are exposed to stressors they cannot overcome subsequently fail to attempt to avoid aversive stimuli (such as a shock). This has been interpreted as a model of depression.

We are interested in how control (or lack of it) affects behavior. Specifically, we are examining what neural circuits mediate the computation of control. Initial experiments point to the involvement of the habenula, and we are currently using a combination of imaging and manipulation to further define the neural system involved.

Selected Publications:

S. Jesuthasan (2010) Fear, anxiety and control in the zebrafish, Dev. Neuro., in press. Review

A. Lee. A. Mathuru, C. Teh, C. Kibat, V. Korzh, T. Penney and S. Jesuthasan (2010) The habenula prevents helpless behavior in larval zebrafish. Current Biology, 20: 2211-2216.

M. Hendricks and S. Jesuthasan (2009)
PHR regulates growth cone pausing at intermediate targets through microtubule disassembly
J. Neurosci., 29: 6593-6598.

S. Jesuthasan and A. Mathuru (2008)
The alarm response in zebrafish: innate fear in a vertebrate genetic model,
J. Neurogenetics, 22, 1-18. Review

M. Hendricks, A. Mathuru, H. Wang, O. Silander, M. Kee and S. Jesuthasan (2008)
Disruption of Esrom and Ryk identifies the roofplate boundary as an intermediate target for commissure formation
Mol. Cell. Neurosci., 37: 271-283

M. Hendricks and S. Jesuthasan (2007)
Asymmetric innervation of the habenula in zebrafish
J. Comp. Neurol., 502: 611-619.

M. Hendricks and S. Jesuthasan (2007)
Electroporation-based methods for in vivo, whole mount and primary culture analysis of zebrafish brain development
Neural Dev., 2:6.

S. Le Guyader, J. Maier and S. Jesuthasan (2005)
Esrom, an ortholog of PAM (Protein Associated with cMyc), regulates pteridine synthesis in the zebrafish
Dev. Biol. 277, 378-386.

J. D?Souza, M. Hendricks, S. Le Guyader, S. Subburaju, B. Grunewald, K. Scholich and S. Jesuthasan (2005)
Formation of the retinotectal projection requires Esrom, an ortholog of PAM (protein associated with Myc),
Development; doi: 10.1242/dev.01578 .

M. Wagle, B, Grunewald, S. Subburaju, C. Barzaghi, S. Le Guyader, J. Chan and S. Jesuthasan, (2004)
EphrinB2a in the zebrafish retinotectal system
J. Neurobiol. 59, 57-65.