Abstract
The cAMP/protein kinase A (PKA) signaling cascade is crucial for synaptic plasticity in a wide variety of species. PKA regulates Ca2+ permeation through NMDA receptors (NMDARs) and induction of NMDAR-dependent synaptic plasticity at the Schaffer collateral to CA1 pyramidal cell synapse. Whereas the role of PKA in induction of NMDAR-dependent LTP at CA1 synapses is established, the identity of PKA isoforms involved in this phenomenon is less clear. Here we report that protein synthesis-independent NMDAR-dependent LTP at the Schaffer collateral-CA1 synapse in the hippocampus is deficient, but NMDAR-dependent LTD is normal, in young (postnatal day 10 (P10)-P14) mice lacking PKA RIIβ, the PKA regulatory protein that links PKA to NMDARs at synaptic sites. In contrast, in young adult (P21-P28) mice lacking PKA RIIβ, LTP is normal and LTD is abolished. These findings indicate that distinct PKA isoforms may subserve distinct forms of synaptic plasticity and are consistent with a developmental switch in the signaling cascades required for LTP induction.
Original language | English (US) |
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Pages (from-to) | 56-65 |
Number of pages | 10 |
Journal | Neuropharmacology |
Volume | 56 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2009 |
Keywords
- CA1 synapses
- Hippocampus
- Long-term depression
- Long-term potentiation
- NMDA receptors
- PKA
- PKA RIIβ knockout mice
- PKA type II regulatory subunit
- Synaptic plasticity
ASJC Scopus subject areas
- Pharmacology
- Cellular and Molecular Neuroscience