TY - JOUR
T1 - Long-term memory deficits in pavlovian fear conditioning in Ca 2+/calmodulin kinase kinase α-deficient mice
AU - Blaeser, Frank
AU - Sanders, Matthew J.
AU - Truong, Nga
AU - Ko, Shanelle
AU - Long, Jun Wu
AU - Wozniak, David F.
AU - Fanselow, Michael S.
AU - Zhuo, Min
AU - Chatila, Talal A.
PY - 2006/12
Y1 - 2006/12
N2 - Signaling by the Ca2+/calmodulin kinase (CaMK) cascade has been implicated in neuronal gene transcription, synaptic plasticity, and long-term memory consolidation. The CaM kinase kinase α (CaMKKα) isoform is an upstream component of the CaMK cascade whose function in different behavioral and learning and memory paradigms was analyzed by targeted gene disruption in mice. CaMKKα mutants exhibited normal long-term spatial memory formation and cued fear conditioning but showed deficits in context fear during both conditioning and long-term follow-up testing. They also exhibited impaired activation of the downstream kinase CaMKIV/Gr and its substrate, the transcription factor cyclic AMP-responsive element binding protein (CREB) upon fear conditioning. Unlike CaMKIV/Gr-deficient mice, the CaMKKα mutants exhibited normal long-term potentiation and normal levels of anxiety-like behavior. These results demonstrate a selective role for CaMKKα in contextual fear memory and suggest that different combinations of upstream and downstream components of the CaMK cascade may serve distinct physiological functions.
AB - Signaling by the Ca2+/calmodulin kinase (CaMK) cascade has been implicated in neuronal gene transcription, synaptic plasticity, and long-term memory consolidation. The CaM kinase kinase α (CaMKKα) isoform is an upstream component of the CaMK cascade whose function in different behavioral and learning and memory paradigms was analyzed by targeted gene disruption in mice. CaMKKα mutants exhibited normal long-term spatial memory formation and cued fear conditioning but showed deficits in context fear during both conditioning and long-term follow-up testing. They also exhibited impaired activation of the downstream kinase CaMKIV/Gr and its substrate, the transcription factor cyclic AMP-responsive element binding protein (CREB) upon fear conditioning. Unlike CaMKIV/Gr-deficient mice, the CaMKKα mutants exhibited normal long-term potentiation and normal levels of anxiety-like behavior. These results demonstrate a selective role for CaMKKα in contextual fear memory and suggest that different combinations of upstream and downstream components of the CaMK cascade may serve distinct physiological functions.
UR - http://www.scopus.com/inward/record.url?scp=33845222689&partnerID=8YFLogxK
U2 - 10.1128/MCB.01452-06
DO - 10.1128/MCB.01452-06
M3 - Article
C2 - 17015467
AN - SCOPUS:33845222689
SN - 0270-7306
VL - 26
SP - 9105
EP - 9115
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 23
ER -