Dorsal hippocampus and classical fear conditioning to tone and context in rats: Effects of local NMDA-receptor blockade and stimulation
Dorsal hippocampus and classical fear conditioning to tone and context in rats: Effects of local NMDA-receptor blockade and stimulation
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DOI：
10.1002/hipo.10115
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发表时间：
2003-01-01
期刊：
影响因子：
3.5
通讯作者：
Feldon, J
中科院分区：
文献类型：
--
作者：
Bast, T;Zhang, WN;Feldon, J
与海马体在学习更复杂的刺激关系中的重要性相一致，但在简单的联想学习中却不重要，背侧海马体通常与经典的恐惧条件反射有关，但与离散刺激（如音调）无关。特别是，一个特定的和核心的作用，在上下文的恐惧条件反射已被归因于背海马N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体介导的机制。本研究的特点是阻断或紧张性刺激背海马NMDA受体的非竞争性NMDA受体拮抗剂MK-801（马来酸地佐环平; 6.25微克/侧）或NMDA（0.7微克/侧），分别对经典的恐惧条件反射的语气和上下文的影响。冷冻被用来测量条件性恐惧。无论条件反射是用音调-电击配对还是无信号的足电击（背景或前景背景条件反射）进行的，条件反射前的NMDA和MK-801输注均导致随后暴露于条件反射背景期间的冻结减少。在一个新的背景下，在随后的音调呈现过程中的冻结，通常是由音调-休克配对的条件反射引起的，MK-801不会损害这种冻结，但在条件反射前注入NMDA会大大减少这种冻结;在音调呈现之前注入NMDA也会减少这种冻结（在一项实验中，该实验涉及在条件反射和随后的音调呈现之前注入NMDA，以评估状态依赖性学习的作用）。评估了非特异性输注效应（感觉运动功能改变，状态依赖性）或输注诱导的背海马损伤是否有助于观察到的条件冻结减少。我们的数据表明，形成恐惧条件反射的背景下，但不是语气，需要NMDA受体介导的机制在背海马。NMDA的作用表明，背侧海马的一些突起也可能参与了对音调的恐惧条件反射。背侧海马和本地NMDA受体介导的过程中的恐惧条件反射的音调和上下文的作用进行了讨论，比较腹侧海马的过程。(C)2003 Wiley-Liss，Inc.
Consistent with the importance of the hippocampus in learning more complex stimulus relations, but not in simple associative learning, the dorsal hippocampus has commonly been implicated in classical fear conditioning to context, but not to discrete stimuli, such as a tone. In particular, a specific and central role in contextual fear conditioning has been attributed to mechanisms mediated by dorsal hippocampal N-methyl-D-aspartate (NMDA)-type glutamate receptors. The present study characterized the effects of blockade or tonic stimulation of dorsal hippocampal NMDA receptors by bilateral local infusion of the noncompetitive NMDA receptor antagonist MK-801 (dizocilpine maleate; 6.25mug/side) or of NMDA (0.7mug/side), respectively, on classical fear conditioning to tone and context in Wistar rats. Freezing was used to measure conditioned fear. Regardless of whether conditioning was conducted with tone-shock pairings or unsignaled footshocks (background or foreground contextual conditioning), both NMDA and MK-801 infusion before conditioning resulted in reduced freezing during subsequent exposure to the conditioning context. Freezing during subsequent tone presentation in a new context, normally resulting from conditioning with tone-shock pairings, was not impaired by MK-801 but was strongly reduced by NMDA infusion before conditioning; this freezing was also reduced by NMDA infusion before tone presentation (in an experiment involving NMDA infusions before conditioning and subsequent tone presentation to assess the role of state-dependent learning). It was assessed whether unspecific infusion effects (altered sensorimotor functions, state dependency) or infusion-induced dorsal hippocampal damage contributed to the observed reductions in conditioned freezing. Our data suggest that formation of fear conditioning to context, but not tone, requires NMDA receptor-mediated mechanisms in the dorsal hippocampus. As indicated by the effects of NMDA, some dorsal hippocampal processes may also contribute to fear conditioning to tone. The role of the dorsal hippocampus and local NMDA receptor-mediated processes in fear conditioning to tone and context is discussed in comparison with ventral hippocampal processes. (C) 2003 Wiley-Liss, Inc.