NMDA receptor plasticity in the perirhinal and prefrontal cortices is crucial for the acquisition of long-term object-in-place associative memory
NMDA receptor plasticity in the perirhinal and prefrontal cortices is crucial for the acquisition of long-term object-in-place associative memory
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DOI：
10.1523/jneurosci.4447-07.2008
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发表时间：
2008-03-12
影响因子：
5.3
通讯作者：
Warburton, E. Clea
中科院分区：
文献类型：
--
作者：
Barker, Gareth R. I.;Warburton, E. Clea
识别记忆的一个关键过程是在物体和遇到它的地方之间形成联系，这一过程已被证明需要周围（PRH）和内侧前额叶（mPFC）皮层。在这里，我们首次证明了在PRH和mPFC中谷氨酸能神经传递对于物体就地联想识别记忆的重要性。通过CNQX单侧阻断大鼠对侧脑半球PRH和mPFC中的AMPA受体，证实了这些皮质区域在物体就位识别记忆的神经网络中起作用。mpfc内输注AP5 （NMDA受体拮抗剂）会损害短期记忆和长期记忆的获得，但对检索没有影响。AP5输注到PRH会破坏长期记忆的获得，但不会破坏短期记忆或检索。值得注意的是，交叉AP5输注到PRH和mPFC都破坏了长期记忆的获得，但对短期记忆没有影响。最后，将选择性海碱酸盐（GLUK5）受体拮抗剂UBP302 [(S)-1-（2-氨基-2羧基乙基）- 3-（2-羧基苄基）嘧啶-2,4-二酮]单侧输注到PRH中，并将AP5单侧输注到对侧mPFC中，显著损害了短期的客体原位联想记忆。这些数据表明，PRH和mPFC对物体就地联想记忆有不同的贡献，并且编码长期记忆而不是短期记忆需要两个皮质区域的NMDA受体同时激活。相比之下，短期的物体原位记忆似乎依赖于PRH中的蓝酸盐受体激活和mPFC中的NMDA受体激活。
A key process for recognition memory is the formation of associations between an object and the place in which it was encountered, a process that has been shown to require the perirhinal (PRH) and medial prefrontal (mPFC) cortices. Here we demonstrate, for the first time, the importance of glutamatergic neurotransmission, within the PRH and mPFC, for object-in-place associative recognition memory. Unilateral blockade of AMPA receptors (by CNQX) in the PRH and mPFC in opposite hemispheres impaired an object-in-place task in rats, confirming that these cortical regions operate within a neural network for object-in-place recognition memory. Intra-mPFC infusions of AP5 (NMDA receptor antagonist) impaired short-term memory and the acquisition of long-term memory, but had no effect on retrieval. AP5 infusions into the PRH disrupted acquisition of long-term memory, but not short-term memory or retrieval. Significantly, crossed AP5 infusions into both the PRH and mPFC disrupted acquisition of long-term memory but were without effect on short-term memory. Finally a unilateral infusion of the selective kainate (GLUK5) receptor antagonist UBP302 [(S)-1-(2-amino-2carboxyethyl)- 3-(2-carboxybenzyl)pyrimidine-2,4-dione] into the PRH combined with a unilateral infusion of AP5 into the contralateral mPFC significantly impaired short-term object-in-place associative memory. These data show that the PRH and mPFC make distinct contributions to object-in-place associative memory and that the encoding of long-term but not short-term memory requires concurrent NMDA receptor activation in both cortical regions. In contrast, short-term object-in-place memory appears to be dependent on kainate receptor activation in the PRH and NMDA receptor activation in the mPFC.