| First Author | Qi M | Year | 1996 |
| Journal | Proc Natl Acad Sci U S A | Volume | 93 |
| Issue | 4 | Pages | 1571-6 |
| PubMed ID | 8643673 | Mgi Jnum | J:31731 |
| Mgi Id | MGI:79218 | Doi | 10.1073/pnas.93.4.1571 |
| Citation | Qi M, et al. (1996) Impaired hippocampal plasticity in mice lacking the Cbeta1 catalytic subunit of cAMP-dependent protein kinase. Proc Natl Acad Sci U S A 93(4):1571-6 |
| abstractText | Neural pathways within the hippocampus undergo use- dependent changes in synaptic efficacy, and these changes are mediated by a number of signaling mechanisms, including cAMP-dependent protein kinase (PKA), The PKA holoenzyme is composed of regulatory and catalytic (C) subunits, both of which exist as multiple isoforms. There are two C subunit genes in mice, C alpha and C beta, and the C beta gene gives rise to several splice variants that are specifically expressed in discrete regions of the brain. We have used homologous recombination in embryonic stem cells to introduce an inactivating mutation into the mouse C beta gene, specifically targeting the C beta(1)- subunit isoform, Homozygous mutants showed normal viability and no obvious pathological defects, despite a complete lack of C beta(1), The mice were analyzed in electrophysiological paradigms to test the role of this isoform in long-term modulation of synaptic transmission in the Schaffer collateral-CA1 pathway of the hippocampus. A high-frequency stimulus produced potentiation in both wild-type and C beta(1)(-/-) mice, but the mutants were unable to maintain the potentiated response, resulting in a late phase of long-term potentiation that was only 30% of controls. Paired pulse facilitation was unaffected in the mutant mice, Low-frequency stimulation produced long- term depression and depotentiation in wild-type mice but failed to produce lasting synaptic depression in the C beta(1)(-/-) mutants, These data provide direct genetic evidence that PKA, and more specifically the C beta(1) isoform, is required for long-term depression and depotentiation, as well as the late phase of long-term potentiation in the Schaffer collateral-CA1 pathway. |
