Protein kinase Mzeta is essential for the induction and maintenance of dopamine-induced long-term potentiation in apical CA1 dendrites

Learn Mem. 2010 Nov 17;17(12):605-11. doi: 10.1101/lm.1991910. Print 2010 Dec.

Abstract

Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory as well as for a cellular model of memory, hippocampal long-term potentiation (LTP) in the CA1 region of the hippocampus. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (L-LTP) through activation of the cAMP/PKA-pathway. In earlier studies we had reported a synergistic interaction of D1/D5-receptor function and N-methyl-D-aspartate (NMDA)-receptors for L-LTP. Furthermore, we have found the requirement of the atypical protein kinase C isoform, protein kinase Mζ (PKMζ) for conventional electrically induced L-LTP, in which PKMζ has been identified as a LTP-specific plasticity-related protein (PRP) in apical CA1-dendrites. Here, we investigated whether the dopaminergic pathway activates PKMζ. We found that application of dopamine (DA) evokes a protein synthesis-dependent LTP that requires synergistic NMDA-receptor activation and protein synthesis in apical CA1-dendrites. We identified PKMζ as a DA-induced PRP, which exerted its action at activated synaptic inputs by processes of synaptic tagging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzazepines / pharmacology
  • Biophysics
  • CA1 Region, Hippocampal / cytology*
  • Dactinomycin / pharmacology
  • Dendrites / drug effects*
  • Dopamine / pharmacology*
  • Dopamine Antagonists / pharmacology
  • Drug Interactions
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Immunosuppressive Agents / pharmacology
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects*
  • Male
  • Neurons / cytology*
  • Neurons / drug effects
  • Patch-Clamp Techniques / methods
  • Peptides / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Protein Synthesis Inhibitors / pharmacology
  • Rats
  • Rats, Wistar
  • Sirolimus / pharmacology
  • Time Factors
  • Valine / analogs & derivatives
  • Valine / pharmacology

Substances

  • Benzazepines
  • Dopamine Antagonists
  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Immunosuppressive Agents
  • Peptides
  • Protein Synthesis Inhibitors
  • SCH 23390
  • Dactinomycin
  • 2-amino-5-phosphopentanoic acid
  • Protein Kinase C
  • protein kinase M zeta, rat
  • Valine
  • Dopamine
  • Sirolimus