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 RIM1α, 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 RIM1α (S413A and V415P) and conclude that PKA-phosphorylation-dependent signaling by RIM1α serine 413 is not required for mfLTP, consistent with conclusions reached from the study of RIM1α 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.