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大鼠背侧海马与对音调及环境的经典恐惧条件反射:局部NMDA受体阻断和刺激的影响

Dorsal hippocampus and classical fear conditioning to tone and context in rats: effects of local NMDA-receptor blockade and stimulation.

作者信息

Bast Tobias, Zhang Wei-Ning, Feldon Joram

机构信息

Behavioral Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schwerzenbach, Switzerland.

出版信息

Hippocampus. 2003;13(6):657-75. doi: 10.1002/hipo.10115.


DOI:10.1002/hipo.10115
PMID:12962312
Abstract

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; 6.25 microg/side) or of NMDA (0.7 microg/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.

摘要

与海马体在学习更复杂刺激关系而非简单联想学习中的重要性相一致,背侧海马体通常与对情境的经典恐惧条件反射有关,而与对离散刺激(如音调)的恐惧条件反射无关。特别是,背侧海马体N-甲基-D-天冬氨酸(NMDA)型谷氨酸受体介导的机制在情境恐惧条件反射中具有特定的核心作用。本研究通过分别双侧局部注射非竞争性NMDA受体拮抗剂MK-801(马来酸氯氮平;6.25微克/侧)或NMDA(0.7微克/侧)来阻断或强直刺激背侧海马体NMDA受体,研究其对Wistar大鼠对音调及情境的经典恐惧条件反射的影响。采用僵立来测量条件性恐惧。无论条件反射是通过音调-电击配对还是无信号电击(背景或前景情境条件反射)进行,在条件反射前注射NMDA和MK-801均会导致随后暴露于条件反射情境时僵立减少。在新情境中随后呈现音调时的僵立,通常由音调-电击配对条件反射引起,不受MK-801影响,但在条件反射前注射NMDA会使其显著减少;在音调呈现前注射NMDA(在一项涉及条件反射前注射NMDA及随后音调呈现以评估状态依赖性学习作用的实验中)也会减少这种僵立。评估了非特异性注射效应(改变感觉运动功能、状态依赖性)或注射引起的背侧海马体损伤是否导致了观察到的条件性僵立减少。我们的数据表明,对情境而非音调的恐惧条件反射的形成需要背侧海马体中NMDA受体介导的机制。如NMDA的作用所示,一些背侧海马体过程可能也有助于对音调的恐惧条件反射。将背侧海马体及局部NMDA受体介导的过程在对音调和情境的恐惧条件反射中的作用与腹侧海马体过程进行了比较讨论。

相似文献

[1]
Dorsal hippocampus and classical fear conditioning to tone and context in rats: effects of local NMDA-receptor blockade and stimulation.

Hippocampus. 2003

[2]
Time-dependent involvement of the dorsal hippocampus in trace fear conditioning in mice.

Hippocampus. 2005

[3]
Effects of pre or posttraining dorsal hippocampus D-AP5 injection on fear conditioning to tone, background, and foreground context.

Hippocampus. 2008

[4]
Interaction between glutamatergic-NMDA and cholinergic-muscarinic systems in classical fear conditioning.

Brain Res Bull. 2008-9-30

[5]
The expression of contextual fear conditioning involves activation of an NMDA receptor-nitric oxide pathway in the medial prefrontal cortex.

Cereb Cortex. 2008-9

[6]
Hypofunction of the dorsal hippocampal NMDA receptors impairs retrieval of memory to partially presented foreground context in a single-trial fear conditioning in rats.

Eur Neuropsychopharmacol. 2006-5

[7]
Amygdaloid GABA, not glutamate neurotransmission or mRNA transcription controls footshock-associated fear arousal in the acoustic startle paradigm.

Neuroscience. 2006

[8]
The ventral hippocampus and fear conditioning in rats: different anterograde amnesias of fear after infusion of N-methyl-D-aspartate or its noncompetitive antagonist MK-801 into the ventral hippocampus.

Behav Brain Res. 2001-11-29

[9]
Post-training excitotoxic lesions of the dorsal hippocampus attenuate forward trace, backward trace, and delay fear conditioning in a temporally specific manner.

Hippocampus. 2002

[10]
The role of group I metabotropic glutamate receptors in acquisition and expression of contextual and auditory fear conditioning in rats - a comparison.

Neuropharmacology. 2006-12

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Neurobiol Stress. 2023-1-23

[3]
Zn inhibits spatial memory and hippocampal place cell representation through high-affinity binding to the NMDA receptor GluN2A subunit.

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[4]
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Exp Neurobiol. 2022-8-31

[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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