Adamec R E
Department of Psychology, Memorial University, St. John's, NFLD, Canada.
Brain Res. 1999 Aug 21;839(1):133-52. doi: 10.1016/s0006-8993(99)01731-x.
Behavioral and physiological effects of partial kindling of the right ventral hippocampus by perforant path (PP) stimulation were investigated in the cat. Partial kindling produced lasting changes in affect (increased defensive response to rats) and predatory attack (decreased pawing and biting attack). Partial kindling also induced long term potentiation (LTP) of amygdala efferent transmission to ventromedial hypothalamus (VMH) and periaqueductal gray (PAG) in left and right hemispheres. LTP of field population spikes evoked in area CA3 by PP stimulation was also observed. LTP was detected using evoked potential methods. These findings parallel previous studies of left PP-CA3 partial kindling. Analysis of covariance removing effects of LTP from behavioral changes suggests that initiation of increased defensiveness at 2 days after completion of partial kindling depended on LTP of left and right amygdalo-VMH and right amygdalo-PAG transmission. From 6 days after kindling onward, increased defensiveness depended on LTP of right amygdalo-PAG transmission. Depotentiation of amygdala efferent LTP by bilateral low frequency amygdala stimulation (LFS) (900 pulses at 1 Hz, once daily for 7 days) selectively reduced LTP in right amygdala efferents. At the same time, defensive, but not predatory attack behavior, was returned to levels seen prior to partial kindling. Both depotentiation and reduction of defensiveness were transient. Defensiveness increased to post-kindling levels by 76 days after LFS. At the same time, LTP was restored in the right amygdalo-PAG pathway. In contrast LTP in the right amygdalo-VMH pathway remained depotentiated. Effects of LFS were not due to damage, as thresholds to evoke amygdala efferent response were unchanged. These findings suggest that lasting change in affect following partial hippocampal kindling depends on LTP of right amygdala efferent transmission to PAG. The findings parallel studies of non-convulsant pharmacological induction of lasting increases in defensiveness and amygdalo-PAG LTP with FG-7142. The parallel between the present findings and the FG-7142 experiments suggests that lasting changes in defensive response are dependent on LTP of right amygdala efferents to the PAG, however produced. The findings suggest further that the spectrum of behavioral changes produced by partial kindling are dependent on changes in a variety of neural circuits, and that amygdala efferent transmission changes are responsible for changes in defensive behavior, but not predatory attack behavior. Clinical implications are discussed.
研究了在猫中通过穿通通路（PP）刺激右侧腹侧海马进行部分点燃所产生的行为和生理效应。部分点燃导致情感方面出现持久变化（对大鼠的防御反应增强）以及捕食性攻击行为改变（抓挠和撕咬攻击减少）。部分点燃还诱导了杏仁核传出至左右半球腹内侧下丘脑（VMH）和导水管周围灰质（PAG）的长期增强（LTP）。同时也观察到PP刺激在CA3区诱发的群体场电位的LTP。使用诱发电位方法检测到了LTP。这些发现与之前关于左侧PP-CA3部分点燃的研究结果相似。通过协方差分析去除LTP对行为变化的影响表明，部分点燃完成后2天防御性增强的起始依赖于左右杏仁核-VMH以及右侧杏仁核-PAG传出通路的LTP。点燃后6天起，防御性增强依赖于右侧杏仁核-PAG传出通路的LTP。通过双侧低频杏仁核刺激（LFS）（1Hz，900个脉冲，每日一次，共7天）使杏仁核传出LTP去增强，选择性地降低了右侧杏仁核传出通路的LTP。与此同时，防御行为而非捕食性攻击行为恢复到部分点燃前的水平。去增强和防御性降低都是短暂的。LFS后76天，防御性恢复到点燃后的水平。与此同时，右侧杏仁核-PAG通路的LTP得以恢复。相比之下，右侧杏仁核-VMH通路的LTP仍处于去增强状态。LFS的效应并非由损伤导致，因为诱发杏仁核传出反应的阈值未发生改变。这些发现表明，海马部分点燃后情感方面的持久变化依赖于右侧杏仁核传出至PAG的LTP。这些发现与使用FG-7142进行的非惊厥性药理学诱导防御性持久增强及杏仁核-PAG LTP的研究结果相似。当前研究结果与FG-7142实验之间的相似性表明，防御反应的持久变化依赖于右侧杏仁核传出至PAG的LTP，无论其如何产生。这些发现进一步表明，部分点燃所产生的行为变化谱依赖于多种神经回路的变化，并且杏仁核传出传递的变化是防御行为而非捕食性攻击行为变化的原因。文中讨论了其临床意义。
