Ca2+/calmodulin kinase kinase at is dispensable for brain development but is required for distinct memories in male, though not in female, mice
(2006) Molecular and Cellular Biology — Vol. 26, n° 23, p. 9094-9104 (2006)
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- 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 alpha (CaMKK alpha), which phosphorylates and activates both CaM kinase I (CaMKI) and CaMKIV, the output kinases of the cascade. We show that CaMKK alpha is dispensable for brain development and long-term potentiation in adult hippocampal CA1 synapses. We find that CaMKK alpha is required for hippocampus-dependent contextual fear memory, but not spatial memory, formation. Surprisingly, CaMKK alpha 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 alpha, while in female mice, contextual fear conditioning induces down-regulation of hippocampal BDNF mRNA expression that does not require CaMKK alpha. Additionally, we demonstrate sex-independent up-regulation in hippocampal nerve growth factor-inducible gene B mRNA expression that does not require CaMKK alpha. Thus, we show that CaMKK alpha has a specific complex role in memory formation in males.
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Mizuno, K., Ris, L., Sanchez-Capelo, A., Godaux, E., & Giese, K. P. (2006). Ca2+/calmodulin kinase kinase at is dispensable for brain development but is required for distinct memories in male, though not in female, mice. Molecular and Cellular Biology, 26(23), 9094-9104. https://doi.org/10.1128/MCB.01221-06 (Original work published 2006)