大鼠额叶皮层参与长时程步入抑制性回避记忆的读出

【作者】 刘芳；

【导师】 李葆明；

【作者基本信息】 复旦大学 ， 神经生物学， 2007， 博士

【摘要】 第一部分:前扣带皮层参与长时程步入抑制性回避记忆的读出已有研究表明,前扣带皮层参与场景恐惧记忆形成。近来科学工作者发现,前扣带皮层参与长时程场景恐惧记忆和空间记忆的读出。为了进一步探讨前扣带皮层在恐惧记忆读出中的作用,我们观察了损毁或失活前扣带皮层对步入抑制性回避记忆读出的影响。本研究表明:损毁前扣带皮层后,大鼠29天和15天恐惧记忆读出受损;记忆读出前使用GABA_A受体激动剂muscimol失活前扣带皮层,损害7天、4天和1天恐惧记忆的读出,但对2小时和6小时恐惧记忆的读出没有影响。这些研究结果提示:大鼠前扣带皮层对于长时程步入抑制性回避记忆的读出是至关重要的,但对于短时步入抑制性回避记忆的读出是不重要的。第二部分:内侧前额叶皮层参与长时程步入抑制性回避记忆读出海马和杏仁体在恐惧记忆读出中的作用及机制已得到广泛研究,但关于前额叶皮层在长时程恐惧记忆读出中作用的相关报道不多。本工作研究了前额叶皮层在抑制性回避记忆读出中的作用及可能机制。研究结果表明:①:记忆读出前30分钟使用GABA_A受体激动剂muscimol失活前额叶皮层,1天、7天恐惧记忆读出受损,但2小时恐惧记忆读出不受影响;②:1天、7天恐惧记忆读出激活前额叶皮层ERK-CREB信号通路;③:恐惧记忆读出前30分钟在前额叶皮层内注射ERK激酶抑制剂PD98059,损害7天恐惧记忆读出,并显著降低前额叶皮层内ERK、CREB磷酸化水平。这些结果提示,长时程抑制性回避记忆的读出需要前额叶皮层ERK-CREB信号通路参与。更多还原

【Abstract】 Part I: The anterior cingulate cortex is involved in retrieval of long-term memory for step-through inhibitory avoidance in ratsIt is known that the anterior cingulate cortex (ACC) is involved in the formation of contextual fear memory. Recent studies showed that the ACC is important for retrieval of spatial memory and contextual fear memory. In order to further examine the role of ACC in fear memory, we investigated the effects of lesion to or inactivation of ACC on the retrieval or expression of step-through inhibitory avoidance (IA) memory. We first examined the effect of lesion to the ACC on long-term memory retrieval. Chemical lesion to the ACC by quinolinic acid severely impaired retrieval of 15-day and 29-day memories for one-trial step-through IA. We then investigated the effect of inactivation of the ACC on short- and long-term memory retrieval. Pre-retrieval inactivation of the ACC by local infusion of muscimol, a selective GABAa receptor agonist, produced severe deficit in 1-day, 4-day and 7-day memories, but had no effect on 2-hour and 6-hour memories. The present results provide evidence that the ACC is important for retrieval of long-term, but not short-term, fear memory for IA. Part II: The medial prefrontal cortex is required for retrieval of long-term memory for one-trial inhibitory avoidance in ratsNeural mechanism underlying memory retrieval has been extensively studied in the hippocampus and amygdala. However, little is known about the role of the prefrontal cortex in memory retrieval. The present study investigated the role of the rat medial prefrontal cortex (mPFC) in retrieval of memory for one-trial step-through inhibitory avoidance (IA). Our results showed that, 1) inactivation of the mPFC by local infusion of the GABA_A-receptor agonist muscimol caused a severe deficit in retrieval of 1-day and 7-day but not 2-hour IA memory; 2) the protein level of phospho-ERK1/2 in the mPFC were significantly increased following retrieval of 1-day and 7-day IA memory, so did the numbers of phospho-ERK (pERK) and phospho-CREB (pCREB) positive neurons; 3) intra-mPFC infusion of the ERK kinase inhibitor PD98095 30 min prior to retrieval significantly reduced both protein levels and/or positive neurons of phospho-ERK1/2 and phospho-CREB, and severely impaired retrieval of 7-day IA memory. The present study provides evidence that the retrieval of long-lasting memory for inhibitory avoidance requires the mPFC and involves the ERK-CREB signaling cascade in this cortical region.更多还原