Protein Phosphatase-1 Regulation in the Induction of Long-Term Potentiation: Heterogeneous Molecular Mechanisms

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Abstract
Protein phosphatase inhibitor-1 (I-1) has been proposed as a regulatory element in the signal transduction cascade that couples postsynaptic calcium influx to long-term changes in synaptic strength. We have evaluated this model using mice lacking I-1. Recordings made in slices prepared from mutant animals and also in anesthetized mutant animals indicated that long-term potentiation (LTP) is deficient at perforant path–dentate granule cell synapses.In vitro, this deficit was restricted to synapses of the lateral perforant path. LTP at Schaffer collateral–CA1 pyramidal cell synapses remained normal. Thus, protein phosphatase-1-mediated regulation of NMDA receptor-dependent synaptic plasticity involves heterogeneous molecular mechanisms, in both different dendritic subregions and different neuronal subtypes. Examination of the performance of I-1 mutants in spatial learning tests indicated that intact LTP at lateral perforant path–granule cell synapses is either redundant or is not involved in this form of learning.