Hippocampal activity, but not plasticity, is required for early consolidation of fear conditioning with a short trace interval

Hippocampal activity, but not plasticity, is required for early consolidation of fear conditioning with a short trace interval
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DOI:
10.1111/j.1460-9568.2007.05493.x
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发表时间:
2007-04-01
影响因子:
3.4
通讯作者:
Gewirtz, Jonathan C.
Gewirtz, Jonathan C.
中科院分区:
医学3区
文献类型:
--
作者:
Burman, Michael A.;Gewirtz, Jonathan C.

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仅当条件刺激(CS)终止和非条件刺激(US)开始(痕迹恐惧条件反射)之间插入时间间隙时,背侧海马才需要进行明确的线索恐惧条件反射。为了检查背侧海马在关联时间上不连续的刺激中的作用并尽量减少上下文线索的潜在贡献,使用相对较短(3秒)的跟踪间隔进行恐惧条件反射。当训练后立即进行时,使用AMPA受体拮抗剂NBQX(3μg/半球)或GABA(A)激动剂蝇蕈醇(5μg/半球)灭活背侧海马会破坏微量恐惧调节。当训练前或训练后 2 小时输注 NBQX 时,微量调节并未受到显着干扰。同样,当 CS 和 US 重叠(延迟调节)时,NBQX 输注无效。此外,海马内输注 NMDA 受体拮抗剂 AP5(5 μg/半球)或 L 型电压门控钙通道(VGCC)阻断剂地尔硫卓(20 或 40 μg/半球)不会损害微量调节。这些数据表明,背侧海马参与短痕迹间隔恐惧调节很大程度上限于记忆巩固的早期阶段,在此期间它介导其他大脑区域的长期记忆的存储。
The dorsal hippocampus is required for explicit cue fear conditioning only when a temporal gap is inserted between conditioned stimulus (CS) termination and unconditioned stimulus (US) onset (trace fear conditioning). To examine the role of the dorsal hippocampus in associating temporally discontiguous stimuli and to minimize the potential contribution of contextual cues, fear conditioning was conducted using a relatively short (3-s) trace interval. Inactivation of the dorsal hippocampus using the AMPA receptor antagonist NBQX (3 mu g/hemisphere) or the GABA(A) agonist muscimol (5 mu g/hemisphere) disrupted trace fear conditioning when conducted immediately following training. Trace conditioning was not disrupted significantly when NBQX was infused either before or 2 h after training. Similarly, NBQX infusions were not effective when the CS and US overlapped (delay conditioning). Moreover, trace conditioning was not impaired by intrahippocampal infusion of either the NMDA receptor antagonist AP5 (5 mu g/hemisphere) or the L-type voltage-gated calcium channel (VGCC) blocker diltiazem (20 or 40 mu g/hemisphere). These data suggest that the involvement of the dorsal hippocampus in short trace interval fear conditioning is largely restricted to the early period of memory consolidation, during which time it mediates the storage of long-term memory in other brain regions.