Differential regulation of CaMKII inhibitor beta protein expression after exposure to a novel context and during contextual fear memory formation.
Understanding of the molecular basis of long-term fear memory (fear LTM) formation provides targets in the treatment of emotional disorders. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is one of the key synaptic molecules involved in fear LTM formation. There are two endogenous inhibitor proteins of CaMKII, CaMKII N alpha and N beta, which can regulate CaMKII activity in vitro. However, the physiological role of these endogenous inhibitors is not known. Here, we have investigated whether CaMKII N beta protein expression is regulated after contextual fear conditioning or exposure to a novel context. Using a novel CaMKII N beta-specific antibody, CaMKII N beta expression was analysed in the naïve mouse brain as well as in the amygdala and hippocampus after conditioning and context exposure. We show that in naïve mouse forebrain CaMKII N beta protein is expressed at its highest levels in olfactory bulb, prefrontal and piriform cortices, amygdala and thalamus. The protein is expressed both in dendrites and cell bodies. CaMKII N beta expression is rapidly and transiently up-regulated in the hippocampus after context exposure. In the amygdala, its expression is regulated only by contextual fear conditioning and not by exposure to a novel context. In conclusion, we show that CaMKII N beta expression is differentially regulated by novelty and contextual fear conditioning, providing further insight into molecular basis of fear LTM.
Radwańska
K
K
Centre for the Cellular Basis of Behaviour, Institute of Psychiatry, King's College London, London, UK.
Tudor-Jones
A A
AA
Mizuno
K
K
Pereira
G S
GS
Lucchesi
W
W
Alfano
I
I
Łach
A
A
Kaczmarek
L
L
Knapp
S
S
Giese
K Peter
KP
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D003214:Conditioning, Classical / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005239:Fear / Q000502:physiology*; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009830:Olfactory Bulb / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2