Beldhuis H J, Everts H G, Van der Zee E A, Luiten P G, Bohus B
Department of Animal Physiology, University of Groningen, Haren, The Netherlands.
Hippocampus. 1992 Oct;2(4):397-409. doi: 10.1002/hipo.450020407.
Protein kinase C (PKC) comprises a family of kinases consisting of nine subspecies that are differentially distributed in the central nervous system. This implies distinct functions. Its involvement is suggested in cellular and molecular mechanisms by which the hippocampus exerts influence on information processing. In this study, it was questioned whether abnormal activity in the neuronal substrate, particularly the hippocampal formation, induced by amygdala kindling indeed impairs spatial memory performance and correlated alpha, beta I/II, and gamma PKC subspecies expression. Rats were trained in a spatial discrimination task (SDT) and simultaneously kindled in the amygdala to induce abnormal, epileptiform activity. Control rats were only trained in the holeboard, a "free choice" maze, in which working (WM) and reference memory (RM) were simultaneously examined. Halfway through and at the end of the experiments the influence of kindling and SDT training on the immunoreactivity for PKC subspecies alpha, beta I/II, and gamma was evaluated in the hippocampal formation. Kindling resulted in a gradual increase in afterdischarge duration and motor seizure (MS) severity. Repeated SDT training ultimately resulted in an asymptotic level of WM and RM performance. As soon as generalized MSs developed, kindled rats failed to improve RM, whereas WM was not influenced. Compared to untrained rats, in trained controls PKC gamma but not PKC alpha beta I/II immunoreactivity was elevated in CA1 pyramidal and dentate gyrus granular cells. Generalized but not partial MSs abolished these alterations in PKC gamma immunoreactivity. The present data indicate that repeated training in a SDT affects the expression of PKC subspecies gamma but not of alpha or beta in the rat hippocampus. Generalized epileptiform activity impair both acquisition of new spatial RM information and PKC gamma expression. It is argued that PKC gamma plays a role in cellular mechanisms through which pathological brain activity impairs certain aspects of spatial memory.
蛋白激酶C（PKC）是一个激酶家族，由九个亚类组成，在中枢神经系统中呈差异分布。这意味着它们具有不同的功能。海马体对信息处理产生影响的细胞和分子机制表明PKC参与其中。在本研究中，有人质疑杏仁核点燃诱导的神经元底物（特别是海马结构）异常活动是否确实会损害空间记忆表现，并与α、βI/II和γPKC亚类表达相关。将大鼠训练进行空间辨别任务（SDT），并同时在杏仁核进行点燃以诱导异常的癫痫样活动。对照大鼠仅在洞板（一种“自由选择”迷宫）中进行训练，在该迷宫中同时检测工作记忆（WM）和参考记忆（RM）。在实验进行到一半时和结束时，评估点燃和SDT训练对海马结构中PKC亚类α、βI/II和γ免疫反应性的影响。点燃导致后放电持续时间和运动性癫痫发作（MS）严重程度逐渐增加。重复的SDT训练最终导致WM和RM表现达到渐近水平。一旦出现全身性MS，点燃大鼠的RM就无法改善，而WM不受影响。与未训练的大鼠相比，在训练对照中，CA1锥体神经元和齿状回颗粒细胞中的PKCγ免疫反应性升高，而PKCαβI/II则没有。全身性而非部分性MS消除了PKCγ免疫反应性的这些变化。目前的数据表明，在SDT中重复训练会影响大鼠海马体中PKC亚类γ的表达，但不会影响α或β的表达。全身性癫痫样活动会损害新空间RM信息的获取和PKCγ表达。有人认为，PKCγ在细胞机制中起作用，通过该机制病理性脑活动会损害空间记忆的某些方面。
