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记忆的奥秘—与短期记忆相关的脑区

       一些电视剧、电影等影视作品中经常会出现具有超常记忆力的天才以及经过培训的特工，他们往往能在很短的时间内记住一长串的看似无序的数字或字母，或者是轻而易举的回忆起刚刚经历的场景中的每一个细节，这种能力肯定让很多观众羡慕不已。然而，科学研究发现：对于毫无顺序的数字或英文字母，普通人能够记忆的极限大约在7位左右，一些记忆力较好的人也只能记住9位左右。这种短时间的记忆又称“工作记忆”，是人们形成“长期记忆”的基础，而一些脑部疾病（如帕金森和精神分裂症）患者中也可观察到工作记忆缺损现象。

但是直到今天，工作记忆形成的生理基础仍未完全研究清楚，许多研究人员仍在此领域进行探索。2015年6月18日的《Nature》上的一篇文章指出海马至前额皮质（vHPC–mPFC）这一输入通路对工作记忆中的空间相关记忆的形成起重要作用。研究人员利用光遗传技术实现了vHPC–mPFC通路的精确抑制，再结合行为学实验结果，得出结论：这一通路的抑制只会对空间相关工作记忆的编码起扰乱作用，而对空间相关工作记忆的维持和提取方面并无十分明显的影响。

此外，2012年12月4日的《PNAS》上的一篇文章也指出大脑前额皮质在工作记忆的形成过程中起重要作用，并且它的作用受中脑多巴胺系统的调控。研究人员先利用功能核磁共振技术找到大脑前额皮质中与工作记忆相关的脑区，然后再结合单脉冲经颅磁刺激技术来测试前额皮质与涉及记忆相关行为之间关系，最终通过对脑干成像发现了多巴胺系统的调节作用。虽然这些只是对工作记忆生理基础的一些基本的研究，但相信随着技术的发展和研究层次的深入，人们终有一天能彻底研究清楚有关记忆的奥秘。

1.论文标题：Hippocampal–prefrontalinput supports spatial encoding in working memory

原文摘要：Spatial working memory, the caching ofbehaviorally relevant spatial cues on a timescale of seconds, is a fundamental constituentof cognition. Although the prefrontal cortex and hippocampus are known tocontribute jointly to successful spatial working memory, the anatomical pathwayand temporal window for the interaction of these structures critical to spatialworking memory has not yet been established. Here we find that directhippocampal–prefrontal afferents are critical for encoding, but not formaintenance or retrieval, of spatial cues in mice. These cues are representedby the activity of individual prefrontal units in a manner that is dependent onhippocampal input only during the cue-encoding phase of a spatial workingmemory task. Successful encoding of these cues appears to be mediated bygamma-frequency synchrony between the two structures. These findings indicate acritical role for the direct hippocampal–prefrontal afferent pathway in thecontinuous updating of task-related spatial information during spatial workingmemory.

全文链接：http://www.nature.com/nature/journal/v522/n7556/full/nature14445.html

2.论文标题：Role of prefrontal cortex and the midbrain dopamine systemin working memory updating

原文摘要：Humans are adept at switching betweengoal-directed behaviors quickly and effectively. The prefrontal cortex (PFC) isthought to play a critical role by encoding, updating, and maintaining internalrepresentations of task context in working memory. It has also beenhypothesized that the encoding of context representations in PFC is regulatedby phasic dopamine gating signals. Here we use multimodal methods to test thesehypotheses. First we used functional MRI (fMRI) to identify regions of PFCassociated with the representation of context in a working memory task. Next weused single-pulse transcranial magnetic stimulation (TMS), guided spatially byour fMRI findings and temporally by previous event-related EEG recordings, todisrupt context encoding while participants performed the same working memorytask. We found that TMS pulses to the right dorsolateral PFC (DLPFC)immediately after context presentation, and well in advance of the response,adversely impacted context-dependent relative to context-independent responses.This finding causally implicates right DLPFC function in context encoding.Finally, using the same paradigm, we conducted high-resolution fMRImeasurements in brainstem dopaminergic nuclei (ventral tegmental area andsubstantia nigra) and found phasic responses after presentation of contextstimuli relative to other stimuli, consistent with the timing of a gatingsignal that regulates the encoding of representations in PFC. Furthermore,these responses were positively correlated with behavior, as well as with responsesin the same region of right DLPFC targeted in the TMS experiment, lendingsupport to the hypothesis that dopamine phasic signals regulate encoding, andthereby the updating, of context representations in PFC.

全文链接：http://www.pnas.org/content/109/49/19900

3.论文标题：Simulation of the capacity and precisionof working memory in the hypodopaminergic state: relevance toschizophrenia

论文摘要：Working memory (WM) impairment has receivedattention as a behavioral characteristic of schizophrenia. Neurobiologicalstudies have led to the hypothesis that a deficit in dopamine transmissionthrough D1 receptors in the prefrontal cortex (PFC) is associated with WMimpairment in schizophrenia. However, empirical approaches that aim to clarifythe nature of the impairment and its underlying mechanism are difficult toenact, especially in unmedicated patients. By contrast, computationalapproaches using biologically plausible models have formed a powerfultheoretical framework for the study of WM impairment in schizophrenia. Thisarticle attempts to directly connect neurobiological findings to theneuropsychological behaviors present in patients with schizophrenia. Using abiologically plausible prefrontal cortical circuit model, we simulatedsustained activity during a simultaneous, multitarget WM task. We subsequentlyanalyzed how dopaminergic modulation via D1 receptor activation alters thecapacity and precision of WM and investigated the underlying mechanism.Hypodopaminergic modulation resulted in imprecision and a reduced capacity inWM primarily due to decreased N-methyl-D-aspartate (NMDA) conductance.Increasing NMDA conductance ameliorated both impairments. These results accountfor the mechanism that underlies WM impairments in schizophrenia and provide atheoretical basis for combination therapy with antipsychotic drugs and drugsthat enhance NMDA receptor function, which is expected to be effective for thetreatment of WM impairments in these patients.

全文链接：http://www.sciencedirect.com/science/article/pii/S0306452215002766