The PTEN phosphatase is essential for long-term depression of hippocampal synapses.
Activity-induced long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission are two types of enduring changes in neuronal connections that are believed to underlie learning and memory functions. Here we show that CA1 synapses in hippocampal slices from PTEN-deficient mice exhibit LTP, but are resistant to LTD. PTEN reduces phosphatidylinositol-3-kinase (PI3-K) activity, and pharmacological inhibition of PI3-K restores LTD in PTEN-deficient mice, suggesting that inhibition of PI3-K by PTEN is necessary for LTD induction. These findings demonstrate a pivotal role for PTEN in LTD, and suggest that alterations in PTEN could have an impact on learning and memory processes.
Wang
Yue
Y
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Cheng
Aiwu
A
Mattson
Mark P
MP
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007858:Learning; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt