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The Journal of Neuroscience, March 8, 2006, 26(10):2808-2813; doi:10.1523/JNEUROSCI.5406-05.2006

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Brief Communications
Impaired Bidirectional Synaptic Plasticity and Procedural Memory Formation in Striatum-Specific cAMP Response Element-Binding Protein-Deficient Mice

Christopher Pittenger,^1 * Stefania Fasano,^3,4 * David Mazzocchi-Jones,⁵ Stephen B. Dunnett,⁵ Eric R. Kandel,^1,2 and Riccardo Brambilla³

¹Center for Neurobiology and Behavior and ²Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, New York 10032, ³San Raffaele Scientific Institute, 20132 Milano, Italy, ⁴Istituto di Psicologia, Facoltà di Medicina, Università degli Studi di Milano, 20134 Milano, Italy, and ⁵School of Biosciences, Cardiff University, Cardiff CF10 3US, United Kingdom

Correspondence should be addressed to Riccardo Brambilla, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy. Email: brambilla.riccardo{at}hsr.it

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.

Key words: striatum; memory formation; learning and memory; transgenic; synaptic plasticity; genetics

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Received Dec. 19, 2005; revised Jan. 27, 2006; accepted Jan. 27, 2006.

Correspondence should be addressed to Riccardo Brambilla, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milano, Italy. Email: brambilla.riccardo{at}hsr.it

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