homeostasis/metabolism
• in transgenics, basal PKA activity in hippocampal extracts (239 pmol/min/mg) is 50% of wild-type (499 pmol/min/mg); when kinase is activated with 5 um cAMP, activity is attenuated by 25% with respect to wild-type mice.
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behavior/neurological
• transgenic mice show decreased ethanol preference and consumption compared to wild-type
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• mutants have normal short term memory in tests but long term memory is severely defective compared to wild-type
(J:38837)
• training mice with a single conditioned stimulus (CS)/ unconditioned stimulus (US) pairing and testing mice 1, 3, 6, and 24 hours after training shows similar responses in transgenic and control mice at 1 hour, but dramatic reduction in contextual fear responses relative to wild-type at 3, 6, and 24 hours post-training; this indicates short term memory is normal in mutants, but long term memory is impaired
(J:110284)
• similar results are obtained when control mice are treated with the PKA inhibitor Rp-cAMPs prior to training
(J:110284)
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• in a probe trial of the Morris water maze test, mutants search less selectively and spend less time in the target quadrant than control mice, but mutants do not have reduced visual acuity or motor coordination
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• mice are more sensitive to ethanol-induced sedation than wild-type
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nervous system
• when four 100 Hz trains are applied to hippocampal slices from mutant mice, it elicits a continually decaying potentiation (fEPSP slopes - 202%, 144% and 107% at 20, 60 and 180 minutes); in wild-type this stimulation induces robust, long-lasting L-LTP (fEPSP slopes - 123%, 199% and 176% at 20, 60 and 180 minutes); early-LTP induced by one or two stimuli is unchanged in mutants
• there is a defect in Schaffer collateral L-LTP
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