Abstract:
Although the phenomenon of memory formation and recall associated with the use of psychotropic drugs has been extensively studied, mechanisms underlying memories for natural reward have not been clarified. Herein, we test the hypothesis that glutamatergic receptors in the dentate gyrus play a role in memories associated with sucrose. We used pellet self-administration protocol to generate memories in two-port nose-poke discrimination task using male Wistar rats. During non-rewarded probe trial, the conditioned animals readily discriminated the active port versus inactive port and showed massive increase in mRNA expression of AMPA receptor subunit genes (gria2, gria3) as well as c-Fos protein in the DG. Access to sweet pellet further enhanced c-Fos expression in the DG. However, animals pre-treated with AMPA receptor antagonist CNQX (intra-DG), on exposure to operant chamber (no pellet), showed decreased discrimination as well as c-Fos expression. We suggest that AMPA receptors in DG mediate recall and consolidation of memories associated with sucrose consumption. CNQX pre-treated animals, if presented with sweet pellet on nose poke, exhibited high discrimination index coupled with increased c-Fos expression. In these CNQX treated rats, the DI was again decreased following administration of NMDA receptor antagonist AP5. We suggest that, although AMPA receptors are blocked, the access to sweet pellet may induce surge of glutamate in the DG, which in turn may reinstate memories via activation of erstwhile silent synapses in NMDA dependant manner.
摘要:
尽管与使用精神药物有关的记忆形成和回忆现象已得到广泛研究,自然奖励记忆的潜在机制尚未得到澄清。在这里,我们检验了以下假设:齿状回中的谷氨酸能受体在与蔗糖相关的记忆中起作用。我们使用颗粒自我给药方案在使用雄性Wistar大鼠的两端口鼻戳辨别任务中产生记忆。在无奖励的探针试验中,条件动物很容易区分活动端口和非活动端口,并显示DG中AMPA受体亚基基因(gria2,gria3)以及c-Fos蛋白的mRNA表达大量增加。获得甜味颗粒进一步增强了DG中的c-Fos表达。然而,用AMPA受体拮抗剂CNQX(内DG)预处理的动物,在暴露于手术室(无颗粒)时,显示降低的歧视以及c-Fos表达。我们建议DG中的AMPA受体介导与蔗糖消耗相关的记忆的回忆和巩固。CNQX预处理动物,如果鼻子戳上有甜颗粒,表现出较高的辨别指数,同时c-Fos表达增加。在这些CNQX治疗的大鼠中,在施用NMDA受体拮抗剂AP5后,DI再次降低。我们建议,虽然AMPA受体被阻断,获得甜味颗粒可能会引起DG中谷氨酸的激增,这反过来又可以通过以NMDA依赖的方式激活以前的沉默突触来恢复记忆。