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Published on: January 4, 2010
Regulation of synaptic strength by protein phosphatase 1
W Morishita1, J H Connor, H Xia
1Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA 94304, USA.
Neuron
|January 5, 2002
Summary
Postsynaptic protein phosphatase 1 (PP1) does not affect basal synaptic strength. However, PP1 is crucial for sustaining long-term depression (LTD) after NMDA receptor activation.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- Synaptic strength is dynamically regulated by various molecular mechanisms.
- Protein phosphatase 1 (PP1) is implicated in synaptic plasticity, but its precise role remains unclear.
- Understanding PP1's function is key to deciphering the molecular basis of learning and memory.
Purpose of the Study:
- To investigate the role of postsynaptic protein phosphatase 1 (PP1) in regulating synaptic strength and long-term depression (LTD) in CA1 pyramidal cells.
- To determine if PP1 directly influences basal synaptic transmission or is involved in activity-dependent plasticity.
Main Methods:
- CA1 pyramidal cells were loaded with peptides disrupting PP1 binding or with active PP1.
- Electrophysiological recordings assessed basal synaptic currents (AMPA and NMDA receptors) and synaptically evoked LTD.
- Immunocytochemistry examined PP1 localization following NMDA receptor activation in cultured neurons.
Main Results:
- Disrupting PP1 binding or activating PP1 did not alter basal synaptic currents mediated by AMPA or NMDA receptors.
- Synaptically evoked LTD was blocked by peptides disrupting PP1 binding.
- PP1 activity enhanced LTD and increased synaptic strength after LTD induction.
- NMDA receptor activation increased the synaptic localization of PP1.
Conclusions:
- Postsynaptic PP1 does not significantly regulate basal synaptic strength.
- PP1 activity is essential for the maintenance of LTD.
- NMDA receptor activation facilitates PP1 recruitment to synapses, enabling its role in LTD.
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