The hippocampus and prefrontal cortex are differentially involved in serial memory retrieval in non-stress and stress conditions

We previously showed that 24 h after learning, mice significantly remembered the first (D1) but not the second (D2) discrimination in a serial spatial task and that an acute stress delivered 5 min before the test phase reversed this memory retrieval pattern.A first experiment evaluated the effects of dorsal hippocampus (HPC) or prefrontal cortex (PFC) lesions, these two brain areas being well-known for their involvement in serial and spatial memory processes. For this purpose, six independent groups of mice were used: non-lesioned (controls), PFC or HPC-lesioned animals, submitted or not to an acute stress (electric footshocks; 0.9 mA). Results show that (i) non-stressed controls as well as PFC-lesioned mice (stressed or not) remembered D1 but not D2; (ii) stressed controls and HPC-lesioned mice (stressed or not) remembered D2 but not D1; (iii) stress significantly increased plasma corticosterone in controls and PFC-lesioned mice, but not in HPC-lesioned mice which already showed a significant plasma corticosterone increase in non-stressed condition.Since data from this first experiment showed that stress inhibited the hippocampal-dependent D1 memory retrieval, a second experiment evaluated the behavioral effect of intrahippocampal corticosterone injection in non-stressed mice. Results show that intrahippocampal corticosterone injection induced a reversal of serial memory retrieval pattern similar to that induced by acute stress.Overall, our study shows that (i) in non-stress condition, the emergence of D1 is HPC-dependent; (ii) in stress condition, the emergence of D2 requires the PFC integrity; moreover, intrahippocampal corticosterone injection mimicked the effects of stress in the CSD task.     

阻碍条件性恐惧记忆消退的原因分析

创伤后应激障碍是个体经历严重应激后形成的一种焦虑障碍,对其治疗的关键是消退由创伤应激导致的条件性恐惧记忆,但目前最有效的暴露疗法并不能真正有效地抑制患者恐惧记忆的表达.对条件性恐惧的动物模型研究发现情绪性增强效应、恐惧记忆二级条件化与再巩固、内侧前额叶皮层功能不足等均能够阻碍条件性恐惧记忆的消退.针对这几个方面可以探索治疗创伤后应激障碍的相应方法.     

情绪加工老化效应的神经机制

行为学研究发现,老年人对消极情绪的辨别、注意和记忆都有所下降,而对积极情绪并未表现出类似的现象。情绪加工老化效应的神经影像学研究发现,老年人在情绪加工过程中边缘系统（尤其杏仁核）的激活强度低于年轻人,但额叶皮层区域的激活却有所增强。研究者对该结果提出了两种假说,一种是功能代偿假说,另一种是策略改变假说。功能代偿假说认为老年人额叶皮层区域的激活增强是为了弥补边缘系统功能的下降,反映了大脑功能的代偿;策略改变假说认为老年人主动使用了不同于年轻人的策略,情绪加工方式的不同导致了两组人群大脑活动的差异。未来这方面研究可以从研究层面、研究方法、研究问题等方面逐步完善     

前额皮层肾上腺素能受体在工作记忆中的作用

前额皮层去甲肾上腺素能神经支配主要来自脑干蓝斑核。前额皮层存在不同类型的肾上腺素能受体。其中突触后α2及β2肾上腺素能受体的激活提高工作记忆;α1及β1肾上腺素能受体的激活损害工作记忆。不同受体是通过激活不同的信号通路发挥对工作记忆的调节作用。来自人类被试的研究结果与对动物的研究结果之间尚存在不一致。了解前额皮层不同肾上腺素受体的作用为开发治疗与前额皮层功能失调相关疾病的药物提供了新的方向。     

View-invariant object category learning, recognition, and search: how spatial and object attention are coordinated using surface-based attentional shrouds

How does the brain learn to recognize an object from multiple viewpoints while scanning a scene with eye movements? How does the brain avoid the problem of erroneously classifying parts of different objects together? How are attention and eye movements intelligently coordinated to facilitate object learning? A neural model provides a unified mechanistic explanation of how spatial and object attention work together to search a scene and learn what is in it. The ARTSCAN model predicts how an object's surface representation generates a form-fitting distribution of spatial attention, or "attentional shroud". All surface representations dynamically compete for spatial attention to form a shroud. The winning shroud persists during active scanning of the object. The shroud maintains sustained activity of an emerging view-invariant category representation while multiple view-specific category representations are learned and are linked through associative learning to the view-invariant object category. The shroud also helps to restrict scanning eye movements to salient features on the attended object. Object attention plays a role in controlling and stabilizing the learning of view-specific object categories. Spatial attention hereby coordinates the deployment of object attention during object category learning. Shroud collapse releases a reset signal that inhibits the active view-invariant category in the What cortical processing stream. Then a new shroud, corresponding to a different object, forms in the Where cortical processing stream, and search using attention shifts and eye movements continues to learn new objects throughout a scene. The model mechanistically clarifies basic properties of attention shifts (engage, move, disengage) and inhibition of return. It simulates human reaction time data about object-based spatial attention shifts, and learns with 98.1% accuracy and a compression of 430 on a letter database whose letters vary in size, position, and orientation. The model provides a powerful framework for unifying many data about spatial and object attention, and their interactions during perception, cognition, and action.     

ENSEMBLE RECORDINGS IN AWAKE RATS: ACHIEVING BEHAVIORAL REGULARITY DURING MULTIMODAL STIMULUS PROCESSING AND DISCRIMINATIVE LEARNING

To meet an increasing need to examine the neurophysiological underpinnings of behavior in rats, we developed a behavioral system for studying sensory processing, attention and discrimination learning in rats while recording firing patterns of neurons in one or more brain areas of interest. Because neuronal activity is sensitive to variations in behavior which may confound the identification of neural correlates, a specific aim of the study was to allow rats to sample sensory stimuli under conditions of strong behavioral regularity. Our behavioral system allows multimodal stimulus presentation and is coupled to modules for delivering reinforcement, simultaneous monitoring of behavior and recording of ensembles of well isolated single neurons. Using training protocols for simple and compound discrimination, we validated the behavioral system with a group of 4 rats. Within these tasks, a majority of medial prefrontal neurons showed significant firing‐rate changes correlated to one or more trial events that could not be explained from significant variation in head position. Thus, ensemble recordings can be combined with discriminative learning tasks under conditions of strong behavioral regularity.     

Brain mechanisms associated with background monitoring of the environment for potentially significant sensory events

Background monitoring is a necessary prerequisite to detect unexpected changes in the environment, while being involved in a primary task. Here, we used fMRI to investigate the neural mechanisms that underlie adaptive goal-directed behavior in a cued task switching paradigm during real response conflict or, more generally, when expectations on the repetitive features of the environment were violated. Unexpected changes in sensory stimulus attributes in the currently unattended stimulus dimension thereby led to activations in a bilateral network comprising inferior lateral frontal, intraparietal, and posterior medial frontal brain regions, independent of whether these attributes elicited a factual response conflict or not. This fronto-parietal network may thus play an important role in adaptive responding to potentially significant events outside the current focus of attention.     

海马结构、前额皮层或尾-壳核损毁对大鼠空间认知能力的影响

本研究的目的是探讨海马结构(HF)、前额皮层(PFC)和尾-壳核(CP)在大鼠空间认知加工中的作用。实验观察到HP或PFC损毁大鼠Morris迷宫学习或记忆作业成绩显著低于CP损毁组和控制组(CG);HF损毁大鼠主要采用与其它各组不同的“非图类”搜索策略。搜索策略的差异提示:HF和PFC在大鼠图认知加工系统中处于不同的功能层次,HF起相对重要的作用。CP几乎不影响大鼠空间认知能力,表现出哺乳类与鸟类同源结构的功能分化倾向。     

Lexical retrieval constrained by sound structure: the role of the left inferior frontal gyrus

Positron emission tomography was used to investigate two competing hypotheses about the role of the left inferior frontal gyrus (IFG) in word generation. One proposes a domain-specific organization, with neural activation dependent on the type of information being processed, i.e., surface sound structure or semantic. The other proposes a process-specific organization, with activation dependent on processing demands, such as the amount of selection needed to decide between competing lexical alternatives. In a novel word retrieval task, word reconstruction (WR), subjects generated real words from heard non-words by the substitution of either a vowel or consonant. Both types of lexical retrieval, informed by sound structure alone, produced activation within anterior and posterior left IFG regions. Within these regions there was greater activity for consonant WR, which is more difficult and imposes greater processing demands. These results support a process-specific organization of the anterior left IFG.     

Broad-Perspective Perceptual Disorder of the Right Hemisphere

Traditional accounts of right-posterior brain injury describe a syndrome of low-level perceptual sequelae producing marked acute dependency and transient safety concerns. The syndrome is also held to spare cognition and to carry a generally favorable long-term prognosis. The present paper reviews publications and anecdotal data that challenge this picture. Recent theoretical expositions and empirical studies stipulate three major cognitive functions of the right posterior association cortex: processing novel input, guiding reactions to emergencies, and anticipating consequences. Appearing benign after acute recovery, the impairment of these processes produces vocational, social and marital dysfunctions that increase as a function of chronicity, ultimately becoming more broadly disabling than focal injuries in other cortical loci. The unique symptom picture and serious implications suggest that the long-term syndrome should be labeled (Broad-Perspective Perceptual Disorder) and incorporated in future clinical taxonomies, underscoring the need for extraordinary long-term assistance and specialized therapeutics. Procedures for assessment and differential diagnosis are outlined.