Decreased NR2B subunit synaptic levels cause impaired long-term potentiation but not long-term depression

Fabrizio Gardoni; Daniela Mauceri; Matteo Malinverno; Federica Polli; Cinzia Costa; Alessandro Tozzi; Sabrina Siliquini; Barbara Picconi; Flaminio Cattabeni; Paolo Calabresi; Monica Di Luca

doi:10.1523/JNEUROSCI.3921-08.2009

Decreased NR2B subunit synaptic levels cause impaired long-term potentiation but not long-term depression

J Neurosci. 2009 Jan 21;29(3):669-77. doi: 10.1523/JNEUROSCI.3921-08.2009.

Authors

Fabrizio Gardoni¹, Daniela Mauceri, Matteo Malinverno, Federica Polli, Cinzia Costa, Alessandro Tozzi, Sabrina Siliquini, Barbara Picconi, Flaminio Cattabeni, Paolo Calabresi, Monica Di Luca

Affiliation

¹ Department of Pharmacological Sciences and Centre of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy. [email protected]

Abstract

The discovery of the molecular mechanisms regulating the abundance of synaptic NMDA receptors is essential for understanding how synaptic plasticity, as well as excitotoxic events, are regulated. However, a complete understanding of the precise molecular mechanisms regulating the composition of the NMDA receptor complex at hippocampal synapse is still missing. Here, we show that 2 h of CaMKII inhibition leads to a specific reduction of synaptic NR2B-containing NMDA receptors without affecting localization of the NR2A subunit; this molecular event is accompanied by a dramatic reduction in the induction of long-term potentiation (LTP), while long-term depression induction is unaffected. The same molecular and functional results were obtained by disrupting NR2B/PSD-95 complex with NR2B C-tail cell permeable peptide (TAT-2B). These data indicate that NR2B redistribution between synaptic and extrasynaptic membranes represents an important molecular disturbance of the glutamatergic synapse and affects the correct induction of LTP.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
CREB-Binding Protein / metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
Cells, Cultured
Disks Large Homolog 4 Protein
Electric Stimulation
Embryo, Mammalian
Enzyme Inhibitors / pharmacology
Enzyme-Linked Immunosorbent Assay / methods
Hippocampus / cytology
Immunoprecipitation
Intracellular Signaling Peptides and Proteins / metabolism
Long-Term Potentiation / drug effects
Long-Term Potentiation / physiology*
Long-Term Synaptic Depression / drug effects
Long-Term Synaptic Depression / physiology*
Membrane Proteins / metabolism
Neurons / cytology*
Neurons / drug effects
Neurons / physiology*
Organ Culture Techniques
Patch-Clamp Techniques
Peptides / pharmacology
Protein Transport / drug effects
Rats
Receptors, N-Methyl-D-Aspartate / metabolism*
Subcellular Fractions / metabolism
Synapses / drug effects
Synapses / metabolism*
Time Factors

Substances

CaMKII inhibitor AIP
Disks Large Homolog 4 Protein
Dlg4 protein, rat
Enzyme Inhibitors
Intracellular Signaling Peptides and Proteins
Membrane Proteins
NR2B NMDA receptor
Peptides
Receptors, N-Methyl-D-Aspartate
CREB-Binding Protein
Calcium-Calmodulin-Dependent Protein Kinase Type 2