GluN2B-containing NMDA receptors and AMPA receptors in medial prefrontal cortex are necessary for odor span in rats.
GluN2B-containing NMDA receptors and AMPA receptors in medial prefrontal cortex are necessary for odor span in rats.
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DOI：
10.3389/fnbeh.2013.00183
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发表时间：
2013
影响因子：
3
通讯作者：
Howland JG
中科院分区：
文献类型：
--
作者：
Davies DA;Greba Q;Howland JG
工作记忆是一种短期记忆，涉及复杂认知所必需的信息的维护和操作。虽然记忆跨度能力作为工作记忆的衡量标准在人类中得到了广泛的研究，但在啮齿类动物中却受到的关注要少得多。我们的目的是通过向内侧前额皮质 (mPFC) 全身注射或输注受体拮抗剂来检查 N-甲基-D-天冬氨酸 (NMDA) 和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 谷氨酸受体在气味跨度能力中的作用。长埃文斯大鼠接受了特征明确的气味跨度任务（OST）的训练。最初，老鼠被训练在沙子中挖掘食物奖励，然后使用带有家用香料香味的沙子进行不匹配的样本歧视训练。然后要求大鼠执行一系列延迟的与样本不匹配的程序，即它们的气味跨度。全身注射广谱 NMDA 受体拮抗剂 3-(2-羧基哌嗪-4-基)丙基-1-膦酸 (CPP) (10 mg/kg) 或 GluN2B 选择性拮抗剂 Ro 25-6981（10 mg/kg，但不是 6 mg/kg）显着降低气味跨度能力。将 GluN2B 选择性拮抗剂 Ro 25-6981（2.5 μg/半球）输注到 mPFC 中可降低跨度能力，这种效果几乎是显着的（p = 0.069）。将 AMPA 受体拮抗剂 6-氰基-7-硝基喹喔啉-2,3-二酮 (CNQX)（1.25 μg/半球）输注到 mPFC 中会降低大鼠在任务中做出选择的跨度能力和潜伏期。这些结果表明大鼠的跨度能力取决于 mPFC 中的离子型谷氨酸受体激活。进一步了解跨度容量背后的电路可能有助于为因精神分裂症和阿尔茨海默病等疾病而导致工作记忆障碍的人开发新型治疗药物。
Working memory is a type of short-term memory involved in the maintenance and manipulation of information essential for complex cognition. While memory span capacity has been extensively studied in humans as a measure of working memory, it has received considerably less attention in rodents. Our aim was to examine the role of the N-methyl-D-aspartate (NMDA) and α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in odor span capacity using systemic injections or infusions of receptor antagonists into the medial prefrontal cortex (mPFC). Long Evans rats were trained on a well-characterized odor span task (OST). Initially, rats were trained to dig for a food reward in sand followed by training on a non-match to sample discrimination using sand scented with household spices. The rats were then required to perform a serial delayed non-match to sample procedure which was their odor span. Systemic injection of the broad spectrum NMDA receptor antagonist 3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) (10 mg/kg) or the GluN2B-selective antagonist Ro 25-6981 (10 mg/kg but not 6 mg/kg) significantly reduced odor span capacity. Infusions of the GluN2B- selective antagonist Ro 25-6981 (2.5 μg/hemisphere) into mPFC reduced span capacity, an effect that was nearly significant (p = 0.069). Infusions of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (1.25 μg/hemisphere) into mPFC reduced span capacity and latency for the rats to make a choice in the task. These results demonstrate span capacity in rats depends on ionotropic glutamate receptor activation in the mPFC. Further understanding of the circuitry underlying span capacity may aid in the novel therapeutic drug development for persons with working memory impairments as a result of disorders such as schizophrenia and Alzheimer’s disease.