Phosphatidylinositol 3 kinase regulates synapse specificity of hippocampal long-term depression

Michael I Daw; Zuner A Bortolotto; Emilia Saulle; Shahid Zaman; Graham L Collingridge; John T R Isaac

doi:10.1038/nn903

Phosphatidylinositol 3 kinase regulates synapse specificity of hippocampal long-term depression

Nat Neurosci. 2002 Sep;5(9):835-6. doi: 10.1038/nn903.

Authors

Michael I Daw¹, Zuner A Bortolotto, Emilia Saulle, Shahid Zaman, Graham L Collingridge, John T R Isaac

Affiliation

¹ MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, University Walk, Bristol BS8 1TD, UK.

PMID: 12161757
DOI: 10.1038/nn903

Abstract

To investigate the role of phosphatidylinositol 3 kinase (PI3 kinase) in hippocampal synaptic plasticity, we used whole-cell patch clamp recordings from rat CA1 neurons to determine the effects of PI3 kinase inhibitors on long-term depression (LTD). PI3 kinase blockade caused a loss of synapse specificity of LTD that was dependent on the co-activation of NMDA-type glutamate receptors (NMDARs) and metabotropic glutamate receptors (mGluRs), and involved release of Ca(2+) from intracellular stores. These findings suggest that the synapse specificity of hippocampal LTD may not be an intrinsic property of this form of homosynaptic plasticity, but rather that it can be regulated by PI3 kinase.

Publication types

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

MeSH terms

Animals
Calcium Signaling / drug effects
Calcium Signaling / physiology
Electric Stimulation
Enzyme Inhibitors / pharmacology
Excitatory Postsynaptic Potentials / drug effects
Excitatory Postsynaptic Potentials / physiology
Hippocampus / cytology
Hippocampus / drug effects
Hippocampus / enzymology*
Neural Inhibition / drug effects
Neural Inhibition / physiology*
Neural Pathways / cytology
Neural Pathways / drug effects
Neural Pathways / enzymology*
Neuronal Plasticity / drug effects
Neuronal Plasticity / physiology*
Phosphatidylinositol 3-Kinases / metabolism*
Phosphoinositide-3 Kinase Inhibitors
Protein Kinase C / antagonists & inhibitors
Protein Kinase C / metabolism
Pyramidal Cells / cytology
Pyramidal Cells / drug effects
Pyramidal Cells / enzymology*
Rats
Receptors, Metabotropic Glutamate / antagonists & inhibitors
Receptors, Metabotropic Glutamate / metabolism
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate / metabolism
Synapses / drug effects
Synapses / enzymology*
Synapses / ultrastructure
Synaptic Transmission / drug effects
Synaptic Transmission / physiology

Substances

Enzyme Inhibitors
Phosphoinositide-3 Kinase Inhibitors
Receptors, Metabotropic Glutamate
Receptors, N-Methyl-D-Aspartate
Protein Kinase C