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Motor Behavior Regulation- Genetics of Learning Behavior

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. The movie above shows a wiltype (left) larvae which habituates to accoustic stimuli, and a habituation mutant (righht) which fails to habituate and hence continues to respond.

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Wolman, M.A., Jain, R.A., Marsden, K.C., Bell, H., Skinner, J., Hayer, K.E., Hogenesch, J.B., Granato, M. 2015: A genome-wide screen identifies PAPP-AA mediated IGFR signaling as a novel regulator of habituation learning. Neuron 85 1200-11.pdf. Preview by Ardie and Rankin pdf. UPENN Press Release!

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