Phosphatidylinositol 3 kinase regulates synapse specificity of hippocampal long-term depression.
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.
Daw
Michael I
MI
MRC Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Bortolotto
Zuner A
ZA
Saulle
Emilia
E
Zaman
Shahid
S
Collingridge
Graham L
GL
Isaac
John T R
JT
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate