title: Acute in vivo genetic rescue demonstrates that phosphorylation of RIM1alpha serine 413 is not required for mossy fiber long-term potentiation.
abstract: While presynaptic, protein kinase A (PKA)-dependent, long-term plasticity has been described in numerous brain regions, the target(s) of PKA and the molecular mechanisms leading to sustained changes in neurotransmitter release remain elusive. Here, we acutely reconstitute mossy fiber long-term potentiation (mfLTP) de novo in the mature brains of mutant mice that normally lack this form of plasticity. These results demonstrate that RIM1alpha, a presynaptic scaffold protein and a potential PKA target, can support mfLTP independent of a role in brain development. Using this approach, we study two mutations of RIM1alpha (S413A and V415P) and conclude that PKA-phosphorylation-dependent signaling by RIM1alpha serine 413 is not required for mfLTP, consistent with conclusions reached from the study of RIM1alpha S413A knockin mice. Together, these results provide insights into the mechanism of mossy fiber LTP and demonstrate a useful acute approach to genetically manipulate mossy fiber synapses in the mature brain.
authors.affiliation: Center for Translational Neuroscience, Department of Neurology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Nicole
authors.initials: N
authors.lastname: Calakos
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000409:Alanine / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D051381:Rats; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D048948:14-3-3 Proteins; C491489:Rims1 protein, rat; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D012694:Serine; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D000409:Alanine