Tinsley C J, Narduzzo K E, Ho J W, Barker G R, Brown M W, Warburton E C
Department of Anatomy, Medical Research Council Centre for Synaptic Plasticity, Bristol University, University Walk, Bristol, UK.
Eur J Neurosci. 2009 Sep;30(6):1128-39. doi: 10.1111/j.1460-9568.2009.06917.x. Epub 2009 Sep 4.
The aim was to investigate the role of calcium-calmodulin-dependent protein kinase (CAMK)II in object recognition memory. The performance of rats in a preferential object recognition test was examined after local infusion of the CAMKII inhibitors KN-62 or autocamtide-2-related inhibitory peptide (AIP) into the perirhinal cortex. KN-62 or AIP infused after acquisition impaired memory tested at 24 h, indicating an involvement of CAMKII in the consolidation of recognition memory. Memory was impaired when KN-62 was infused at 20 min after acquisition or when AIP was infused at 20, 40, 60 or 100 min after acquisition. The time-course of CAMKII activation in rats was further examined by immunohistochemical staining for phospho-CAMKII(Thre286)alpha at 10, 40, 70 and 100 min following the viewing of novel and familiar images. At 70 min, processing novel images resulted in more phospho-CAMKII(Thre286)alpha-stained neurons in the perirhinal cortex than did the processing of familiar images, consistent with the viewing of novel images increasing the activity of CAMKII at this time. This difference was eliminated by prior infusion of AIP. These findings establish that CAMKII is active within the perirhinal region between approximately 20 and 100 min following learning and then returns to baseline. Thus, increased CAMKII activity is essential for the consolidation of long-term object recognition memory but continuation of that increased activity throughout the 24 h memory delay is not necessary for maintenance of the memory.
本研究旨在探讨钙调蛋白依赖性蛋白激酶（CAMK）II在物体识别记忆中的作用。在将CAMKII抑制剂KN-62或自身钙调蛋白相关抑制肽（AIP）局部注入大鼠的嗅周皮层后，检测其在优先物体识别测试中的表现。在习得后注入KN-62或AIP会损害24小时后测试的记忆，表明CAMKII参与了识别记忆的巩固。在习得后20分钟注入KN-62或在习得后20、40、60或100分钟注入AIP时，记忆均受损。通过对观看新图像和熟悉图像后10、40、70和100分钟的磷酸化CAMKII（苏氨酸286）α进行免疫组织化学染色，进一步研究了大鼠中CAMKII激活的时间进程。在70分钟时，与处理熟悉图像相比，处理新图像导致嗅周皮层中磷酸化CAMKII（苏氨酸286）α染色的神经元更多，这与此时观看新图像增加了CAMKII的活性一致。预先注入AIP可消除这种差异。这些发现表明，CAMKII在学习后约20至100分钟内在嗅周区域内处于活跃状态，然后恢复到基线水平。因此，增加的CAMKII活性对于长期物体识别记忆的巩固至关重要，但在整个24小时的记忆延迟期间持续保持这种增加的活性对于记忆的维持并非必要。
