CREB selectively controls learning-induced structural remodeling of neurons
- Silvia Middei1,2,10,
- Alida Spalloni3,
- Patrizia Longone3,
- Christopher Pittenger4,
- Shane M. O'Mara7,
- Hélène Marie8,9 and
- Martine Ammassari-Teule1,2,10
- 1CNR-National Research Council, Rome 00143, Italy
- 2Experimental Neurology Unit, Santa Lucia Foundation, Rome 00143, Italy
- 3Molecular Neurobiology Unit, Santa Lucia Foundation, Rome 00143, Italy
- 4Department of Psychiatry and Psychology, Yale University, New Haven, Connecticut 06508, USA
- 5Yale Child Study Center, and Yale University, New Haven, Connecticut 06508, USA
- 6Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut 06508, USA
- 7Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland
- 8Laboratory of Molecular Mechanisms of Synaptic Plasticity, European Brain Research Institute, Rome 00143, Italy
Abstract
The modulation of synaptic strength associated with learning is post-synaptically regulated by changes in density and shape of dendritic spines. The transcription factor CREB (cAMP response element binding protein) is required for memory formation and in vitro dendritic spine rearrangements, but its role in learning-induced remodeling of neurons remains elusive. Using transgenic mice conditionally expressing a dominant-negative CREB (CREBS133A: mCREB) mutant, we found that inhibiting CREB function does not alter spine density, spine morphology, and levels of polymerized actin in naive CA1 neurons. CREB inhibition, however, impaired contextual fear conditioning and produced a learning-induced collapse of spines associated with a blockade of learning-dependent increase in actin polymerization. Blocking mCREB expression with doxycycline rescued memory and restored a normal pattern of learning-induced spines, demonstrating that CREB controls structural adaptations of neurons selectively involved in memory formation.
Footnotes
- Received January 27, 2012.
- Accepted May 7, 2012.
- © 2012 Cold Spring Harbor Laboratory Press