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Motor Behavior Regulation- Genetics of Learning Behavior

In response to experiences with their environment, organisms constantly update their behavior through the processes of sensorimotor integration and learning. We have previously established larval zebrafish as a genetic model in which to study sensorimotor gating, a process in which non-salient sensory information is gated (Burgess & Granato, 2007). Zebrafish also display more complex, decision like behaviors, and we have recently uncovered distinct retinal pathways regulating this process (Burgess, Schoch & Granato, 2010).

A major ongoing effort in the lab is the molecular-genetic basis of learning. The parameters and rules for acquisition and storage of learned information are quite similar across different species, suggesting conservation of the underlying molecular mechanisms. A simple form of learning is non-associative learning, which is defined as a change in attention directed towards a stimulus. A decrease in attention towards an irrelevant stimulus is defined as habituation, and in humans, habituation deficits have been identified as a major feature of several cognitive disorders, including schizophrenia. Despite its general importance, the molecular mechanisms that drive learning, including habituation, are poorly understood. Zebrafish show a remarkable capacity for behavioral plasticity, and we find that larvae exhibit non-associative learning (short-term habituation) with landmark behavioral and pharmacological characteristics. Using an automated system to record and quantify motor behavior kinematics, we have developed a high-throughput behavioral assay for non-associative learning in larval zebrafish. This set-up allows us to perform genetic as well as small molecule screens for genes and pathways underlying non-associative learning.
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Wolman, M.A., DeGroh, E., McBride, S.M., Jongens, T.A., Granato*, M., Epstein*, J.A. (*senior co-authors) 2014. Modulation of cAMP and Ras signaling pathways improve distinct behavioral deficits in a zebrafish model of Neurofibromatosis Type 1. Cell Reports 8, 2014. pdf UPENN Press Release

Wolman, M., Jain, R., Liss, L. & Granato, M. 2011. Chemical modulation of memory formation in larval zebrafish. pdf

Wolman, M., Granato, M. 2011. Behavioral genetics in larval zebrafish-learning from the young. Developmental Neurobiology.pdf

Burgess, H.A, Schoch, H., Granato, M. 2010. Distinct retinal pathways drive spatial orientation behaviors in zebrafish navigation. Current Biology, 20, 381-386. pdf

Burgess, H. A., Granato, M. 2007. Sensorimotor gating of the startle response in larval zebrafish. J. Neuroscience 27(18):4987-94. pdf