Protein phosphatase-1 regulation in the induction of long-term potentiation: Heterogeneous molecular mechanisms

Protein phosphatase inhibitor-1 (I-1) has been proposed as a regulatory ele ment in the signal transduction cascade that couples postsynaptic calcium i nflux to long-term changes in synaptic strength. We have evaluated this mod el using mice lacking I-1. Recordings made in slices prepared from mutant a nimals and also in anesthetized mutant animals indicated that long-term pot entiation (LTP) is deficient at perforant path-dentate granule cell synapse s. In vitro, this deficit was restricted to synapses of the lateral perfora nt path. LTP at Schaffer collateral-CA1 pyramidal cell synapses remained no rmal. Thus, protein phosphatase-1-mediated regulation of NMDA receptor-depe ndent synaptic plasticity involves heterogeneous molecular mechanisms, in b oth different dendritic subregions and different neuronal subtypes. Examina tion of the performance of I-1 mutants in spatial learning tests indicated that intact LTP at lateral perforant path-granule cell synapses is either r edundant or is not involved in this form of learning.