Impaired bidirectional synaptic plasticity and procedural memory formation in striatum-specific cAMP response element-binding protein-deficient mice.
The striatum has a well documented role in procedural learning and memory. However, the synaptic and molecular mechanisms of acquisition and storage of this form of memory remain poorly understood. We examined procedural memory and plasticity in transgenic mice reversibly expressing a dominant-negative cAMP response element-binding protein (CREB) mutant in the dorsal striatum. In these transgenic mice, corticostriatal long-term potentiation and depression are abolished, indicating that CREB function is essential for bidirectional long-term synaptic plasticity in this structure. Importantly, CREB-deficient animals show reversible alterations in several forms of striatum-dependent memory, including footshock avoidance learning and "response" learning in the cross maze. These findings implicate transcriptional regulation by CREB family transcription factors in striatum-dependent information processing and provide the first clear correlation between procedural learning and memory and synaptic plasticity at the corticostriatal synapse.
Pittenger
Christopher
C
Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Fasano
Stefania
S
Mazzocchi-Jones
David
D
Dunnett
Stephen B
SB
Kandel
Eric R
ER
Brambilla
Riccardo
R
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000166:cytology* / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000172:deficiency*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000235:genetics*; D018408:Patch-Clamp Techniques / Q000379:methods; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein