This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.01221-06v1 26/23/9094    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mizuno, K. Articles by Giese, K. P. Search for Related Content PubMed PubMed Citation Articles by Mizuno, K. Articles by Giese, K. P.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2006, p. 9094-9104, Vol. 26, No. 23
0270-7306/06/$08.00+0     doi:10.1128/MCB.01221-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Ca²⁺/Calmodulin Kinase Kinase Is Dispensable for Brain Development but Is Required for Distinct Memories in Male, though Not in Female, Mice

Keiko Mizuno,¹ Laurence Ris,² Amelia Sánchez-Capelo,¹ Emile Godaux,² and K. Peter Giese^1,*

Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, United Kingdom,¹ Department of Neurosciences, University of Mons—Hainaut, 7000 Mons, Belgium²

Received 6 July 2006/ Returned for modification 12 September 2006/ Accepted 18 September 2006

In neurons, the Ca²⁺/calmodulin (CaM) kinase cascade transduces Ca²⁺ signaling into gene transcription. The CaM kinase cascade is known to be important for brain development as well as memory formation in adult brain, although the functions of some cascade members remain unknown. Here we have generated null and hypomorphic mutants to study the physiological role of CaM kinase kinase (CaMKK), which phosphorylates and activates both CaM kinase I (CaMKI) and CaMKIV, the output kinases of the cascade. We show that CaMKK is dispensable for brain development and long-term potentiation in adult hippocampal CA1 synapses. We find that CaMKK is required for hippocampus-dependent contextual fear memory, but not spatial memory, formation. Surprisingly, CaMKK is important for contextual fear memory formation in males but not in females. We show that in male mice, contextual fear conditioning induces up-regulation of hippocampal mRNA expression of brain-derived neurotrophic factor (BDNF) in a way that requires CaMKK, while in female mice, contextual fear conditioning induces down-regulation of hippocampal BDNF mRNA expression that does not require CaMKK. Additionally, we demonstrate sex-independent up-regulation in hippocampal nerve growth factor-inducible gene B mRNA expression that does not require CaMKK. Thus, we show that CaMKK has a specific complex role in memory formation in males.

Published ahead of print on 2 October 2006.

Present address: Institute of Psychiatry, King's College London, London SE5 8AF, United Kingdom.

This article has been cited by other articles:

• Antunes-Martins, A., Mizuno, K., Irvine, E. E., Lepicard, E. M., Giese, K. P. (2007). Sex-dependent up-regulation of two splicing factors, Psf and Srp20, during hippocampal memory formation. Learn. Mem. 14: 693-702 [Abstract] [Full Text]