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

P B Allen, O Hvalby, Kendall R. Van Keuren-Jensen, Michael L Errington, Michele Ramsay, F A Chaudhry, Timothy V P Bliss, J Storm-Mathisen, R G Morris, P.K. Andersen, Paul Greengard

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)3537-43
Number of pages7
JournalJournal of Neuroscience
Volume20
Issue number10
Publication statusPublished - 15 May 2000

Keywords

  • Animals
  • Carrier Proteins
  • Dentate Gyrus
  • Excitatory Postsynaptic Potentials
  • Female
  • Gene Expression
  • Intracellular Signaling Peptides and Proteins
  • Long-Term Potentiation
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Neuronal Plasticity
  • Perforant Pathway
  • Phosphoprotein Phosphatases
  • Phosphoproteins
  • Protein Phosphatase 1
  • Pyramidal Cells
  • RNA-Binding Proteins
  • Space Perception
  • Synapses
  • Water
  • Journal Article
  • Research Support, U.S. Gov't, P.H.S.

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