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 wildtype (left) larvae which habituates to acoustic stimuli, and a habituation mutant (right) which fails to habituate and hence continues to respond.
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Randlett, O., Haesemeyer, M., Shoenhard, H., Schier, A.F., Engert, F., Granato, M. (2019) Distributed plasticity drives visual habituation learning in larval zebrafish. Current Biology, 8;28(9):1337. pdf
Marsden K.C., Jain, R. A. Jain, Wolman M.A., Nelson J.C., Shoenhard, H., Echeverry F.A., Christina Szi, C., Bell, H., Skinner, J., Cobbs E.N., Sawada, K., Zamora, A, Pereda, A.E., Granato, M. (2018) A forward genetic screen identifies the G-protein coupled receptor CaSR as a regulator of sensorimotor decision making. Current Biology, 7;28(9):1357-1369. pdfMarsden K.C., Jain, R. Wolman M.A., Echeverry F.A., Nelson J.C., Hayer, K., Miltenberg, B.,Pereda, A.E., Granato, M. (2018) A Cyfip2 dependent excitatory interneuron pathway established the innate startle threshold. Cell Reports, 17;23(3):878-887. pdf
Jain, R. A. Jain, Wolman M.A., Marsden K.C. Nelson J.C., Shoenhard, H., Echeverry F.A., Christina Szi, C., Bell, H., Skinner, J., Cobbs E.N., Sawada, K., Zamora, A, Pereda, A.E., Granato, M. (2018) A forward genetic screen identifies the G-protein coupled receptor CaSR as a regulator of sensorimotor decision making. Current Biology, 7;28(9):1357-1369. pdf
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