Parallel instabilities of long-term potentiation, place cells, and learning caused by decreased protein kinase A activity.
To further elucidate the links among synaptic plasticity, hippocampal place cells, and spatial memory, place cells were recorded from wild-type mice and transgenic "R(AB)" mice with reduced forebrain protein kinase A (PKA) activity after introduction into a novel environment. Place cells in both strains were similar during the first exposure and were equally stable for recording sessions separated by 1 hr. Place cell stability in wild-type mice was unchanged for sessions separated by 24 hr but was reduced in R(AB) mice over the longer interval. This stability pattern parallels both the reduced late-phase long-term potentiation in hippocampal slices from R(AB) mice and the amnesia for context fear conditioning seen in R(AB) mice 24 but not 1 hr after training. The similar time courses of synaptic, network, and behavioral instability suggest that the genetic reduction of PKA activity is responsible for the defects at each level and support the idea that hippocampal synaptic plasticity is important in spatial memory.
Rotenberg
A
A
Department of Physiology, State University of New York-Brooklyn, Brooklyn, New York 11203, USA.
Abel
T
T
Hawkins
R D
RD
Kandel
E R
ER
Muller
R U
RU
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001070:Appetitive Behavior / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000172:deficiency / Q000378:metabolism*; D004567:Electrodes, Implanted; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008568:Memory / Q000502:physiology; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology; D017966:Pyramidal Cells / Q000201:enzymology / Q000502:physiology*; D013028:Space Perception / Q000502:physiology*; D013037:Spatial Behavior / Q000502:physiology
D017868:Cyclic AMP-Dependent Protein Kinases