Abl Family Nonreceptor Tyrosine Kinases Modulate Short-Term Synaptic Plasticity

1 Department of Genetics; 2 Department of Molecular Biophysics and Biochemistry, and 3 Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520; and 4 Organic Synthesis Core Facility, Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 Moresco, Eva Marie Yang, Alfred J. Scheetz, William G. Bornmann, Anthony J. Koleske, and Reiko Maki Fitzsimonds. Abl Family Nonreceptor Tyrosine Kinases Modulate Short-Term Synaptic Plasticity. J. Neurophysiol. 89: 1678-1687, 2003. Abl family nonreceptor tyrosine kinases regulate cell morphogenesis through functional interactions with the actin cytoskeleton. The vertebrate Abl family kinases, Abl and Arg, are expressed in the adult mouse brain, where they may regulate actin cytoskeletal dynamics in mature neurons. Using immunoelectron microscopy, we have localized Abl and Arg to the pre- and postsynaptic compartments of synapses in the mouse hippocampal area CA1. Paired-pulse facilitation (PPF) was significantly reduced at the Schaffer collateral-CA1 (SC-CA1) excitatory synapses in hippocampal slices from abl / and arg / mice as compared with wild-type mice. Furthermore, treatment of wild-type slices with the specific Abl family kinase inhibitor STI571 also reduced PPF. Basal synaptic transmission, posttetanic potentiation (PTP), long-term potentiation (LTP), and long-term depression (LTD) were similar to wild-type controls in abl / and arg / slices and in STI571-treated wild-type slices. These results indicate that an important function of Abl and Arg is to modulate synaptic efficacy via a presynaptic mechanism during repetitive activation.