Zhang W N, Bast T, Feldon J
Behavioral Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, Postfach, CH 8603 Schwerzenbach, Switzerland.
Behav Brain Res. 2001 Nov 29;126(1-2):159-74. doi: 10.1016/s0166-4328(01)00256-x.
Previous studies on hippocampal involvement in classical fear conditioning mainly focused on the dorsal hippocampus and conditioning to a context. However, in line with the strong interconnectivity of the ventral hippocampus with amygdala and nucleus accumbens, more recent studies indicated an even more global role for the ventral hippocampus in fear conditioning. The present study examined the formation of classical fear conditioning to explicit and contextual cues following stimulation or blockade of N-methyl-D-aspartate (NMDA) receptors in the ventral hippocampus. NMDA (0.5 microg/side) or the noncompetitive NMDA antagonist MK-801 (dizocilpine; 6.25 microg/side) were bilaterally infused into the ventral hippocampus of Wistar rats before fear conditioning to explicit and contextual cues. Conditioned fear was assessed using an automated measurement of freezing. NMDA stimulation of the ventral hippocampus blocked fear conditioning to both the tone and the context. MK-801 selectively blocked fear conditioning to the context. Our results support that the ventral hippocampus plays a role in the formation of classical fear conditioning. The specific anterograde amnesia for fear to a context after MK-801 infusion into the ventral hippocampus indicates that formation of classical fear conditioning to a context but not to a tone requires activation of NMDA receptor-mediated processes in the ventral hippocampus. Given that NMDA stimulation of the ventral hippocampus disrupts also processes not mediated by NMDA receptors, the complete anterograde amnesia following NMDA infusion into the ventral hippocampus might be due to the concurrent severe disruption of normal ventral hippocampal activity. However, strong stimulation of the ventral hippocampus might also disrupt fear conditioning by interfering with processes in the projection areas of the ventral hippocampus, such as the amygdala or the nucleus accumbens. In addition, we report that MK-801 (6.25 microg/side) infusion into the ventral hippocampus increased locomotor activity in the open field.
先前关于海马体参与经典恐惧条件反射的研究主要集中在背侧海马体以及对情境的条件反射。然而，鉴于腹侧海马体与杏仁核和伏隔核之间存在紧密的相互连接，最近的研究表明腹侧海马体在恐惧条件反射中发挥着更为广泛的作用。本研究检测了在腹侧海马体中刺激或阻断N-甲基-D-天冬氨酸（NMDA）受体后，对明确线索和情境线索的经典恐惧条件反射的形成情况。在对Wistar大鼠进行针对明确线索和情境线索的恐惧条件反射训练之前，将NMDA（0.5微克/侧）或非竞争性NMDA拮抗剂MK-801（地卓西平；6.25微克/侧）双侧注入其腹侧海马体。使用自动测量僵住行为的方法评估条件性恐惧。腹侧海马体的NMDA刺激阻断了对音调以及情境的恐惧条件反射。MK-801选择性地阻断了对情境的恐惧条件反射。我们的结果支持腹侧海马体在经典恐惧条件反射的形成中发挥作用。将MK-801注入腹侧海马体后，对情境恐惧的特异性顺行性遗忘表明，对情境而非对音调的经典恐惧条件反射的形成需要腹侧海马体中NMDA受体介导的过程被激活。鉴于腹侧海马体的NMDA刺激也会破坏非NMDA受体介导的过程，将NMDA注入腹侧海马体后出现的完全顺行性遗忘可能是由于同时严重破坏了腹侧海马体的正常活动。然而，腹侧海马体的强烈刺激也可能通过干扰腹侧海马体投射区域（如杏仁核或伏隔核）的过程来破坏恐惧条件反射。此外，我们报告将MK-801（6.25微克/侧）注入腹侧海马体会增加旷场中的运动活动。
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