Maren S, Aharonov G, Fanselow M S
Department of Psychology and Neuroscience Program, University of Michigan, Ann Arbor 48109-1109, USA.
Behav Brain Res. 1997 Nov;88(2):261-74. doi: 10.1016/s0166-4328(97)00088-0.
Electrolytic lesions of the dorsal hippocampus (DH) produce deficits in both the acquisition and expression of conditional fear to contextual stimuli in rats. To assess whether damage to DH neurons is responsible for these deficits, we performed three experiments to examine the effects of neurotoxic N-methyl-D-aspartate (NMDA) lesions of the DH on the acquisition and expression of fear conditioning. Fear conditioning consisted of the delivery of signaled or unsignaled footshocks in a novel conditioning chamber and freezing served as the measure of conditional fear. In Experiment 1, posttraining DH lesions produced severe retrograde deficits in context fear when made either 1 or 28, but not 100, days following training. Pretraining DH lesions made 1 week before training did not affect contextual fear conditioning. Tone fear was impaired by DH lesions at all training-to-lesion intervals. In Experiment 2, posttraining (1 day), but not pretraining (1 week), DH lesions produced substantial deficits in context fear using an unsignaled shock procedure. In Experiment 3, pretraining electrolytic DH lesions produced modest deficits in context fear using the same signaled and unsignaled shock procedures used in Experiments 1 and 2, respectively. Electrolytic, but not neurotoxic, lesions also increased pre-shock locomotor activity. Collectively, this pattern of results reveals that neurons in the DH are not required for the acquisition of context fear, but have a critical and time-limited role in the expression of context fear. The normal acquisition and expression of context fear in rats with neurotoxic DH lesions made before training may be mediated by conditioning to unimodal cues in the context, a process that may rely less on the hippocampal memory system.
背侧海马体（DH）的电解损伤会导致大鼠对情境刺激的条件性恐惧在习得和表达方面出现缺陷。为了评估DH神经元的损伤是否是这些缺陷的原因，我们进行了三项实验，以研究DH的神经毒性N-甲基-D-天冬氨酸（NMDA）损伤对恐惧条件反射的习得和表达的影响。恐惧条件反射包括在一个新颖的条件反射箱中给予有信号或无信号的足部电击，而僵住作为条件性恐惧的衡量指标。在实验1中，训练后1天或28天进行DH损伤会导致情境恐惧出现严重的逆行性缺陷，但训练后100天进行损伤则不会。训练前1周进行的DH损伤不影响情境恐惧条件反射。在所有训练至损伤的间隔时间内，DH损伤都会损害音调恐惧。在实验2中，使用无信号电击程序时，训练后（1天）而非训练前（1周）进行的DH损伤会导致情境恐惧出现显著缺陷。在实验3中，分别使用与实验1和实验2相同的有信号和无信号电击程序，训练前进行的电解性DH损伤会导致情境恐惧出现适度缺陷。电解损伤而非神经毒性损伤也会增加电击前的运动活动。总体而言，这一结果模式表明，DH中的神经元对于情境恐惧的习得并非必需，但在情境恐惧的表达中具有关键且有时限的作用。训练前进行神经毒性DH损伤的大鼠中情境恐惧的正常习得和表达可能是由对情境中单峰线索的条件反射介导的，这一过程可能较少依赖海马记忆系统。
