Barnes C A, Jung M W, McNaughton B L, Korol D L, Andreasson K, Worley P F
Department of Psychology, University of Arizona, Tucson 85724.
J Neurosci. 1994 Oct;14(10):5793-806. doi: 10.1523/JNEUROSCI.14-10-05793.1994.
The prediction that "saturation" of LTP/LTE at hippocampal synapses should impair spatial learning was reinvestigated in the light of a more specific consideration of the theory of Hebbian associative networks, which predicts a nonlinear relationship between LTP "saturation" and memory impairment. This nonlinearity may explain the variable results of studies that have addressed the effects of LTP "saturation" on behavior. The extent of LTP "saturation" in fascia dentata produced by the standard chronic LTP stimulation protocol was assessed both electrophysiologically and through the use of an anatomical marker (activation of the immediate-early gene zif268). Both methods point to the conclusion that the standard protocols used to induce LTP do not "saturate" the process at any dorsoventral level, and leave the ventral half of the hippocampus virtually unaffected. LTP-inducing, bilateral perforant path stimulation led to a significant deficit in the reversal of a well-learned spatial response on the Barnes circular platform task as reported previously, yet in the same animals produced no deficit in learning the Morris water task (for which previous results have been conflicting). The behavioral deficit was not a consequence of any after-discharge in the hippocampal EEG. In contrast, administration of maximal electroconvulsive shock led to robust zif268 activation throughout the hippocampus, enhancement of synaptic responses, occlusion of LTP produced by discrete high-frequency stimulation, and spatial learning deficits in the water task. These data provide further support for the involvement of LTP-like synaptic enhancement in spatial learning.
鉴于对赫布联想网络理论的更具体考量，即该理论预测长时程增强（LTP）“饱和”与记忆损伤之间存在非线性关系，对“海马突触处LTP/LTE的‘饱和’会损害空间学习”这一预测进行了重新研究。这种非线性可能解释了那些探讨LTP“饱和”对行为影响的研究结果的变异性。通过电生理学方法以及使用解剖学标记物（即刻早期基因zif268的激活），评估了标准慢性LTP刺激方案在齿状回中产生的LTP“饱和”程度。两种方法均指向同一个结论：用于诱导LTP的标准方案在任何背腹水平都不会使该过程“饱和”，并且海马体的腹侧部分实际上未受影响。如先前报道的那样，诱导LTP的双侧穿通路径刺激导致在巴恩斯圆形平台任务中对已熟练掌握的空间反应的反转出现显著缺陷，但在同一批动物中，在学习莫里斯水迷宫任务时未产生缺陷（此前针对该任务的结果存在矛盾）。行为缺陷并非海马脑电图中任何后放电的结果。相比之下，给予最大电惊厥休克会导致整个海马体中zif268的强烈激活、突触反应增强、离散高频刺激产生的LTP被阻断以及水迷宫任务中的空间学习缺陷。这些数据为类似LTP的突触增强参与空间学习提供了进一步支持。
