纳络酮用于改善小鼠学习记忆障碍的研究

采用口服氯化铝建立小鼠学习记忆障碍模型,应用跳台法观察了纳络酮对铝(Al)中毒所致小鼠学习记忆障碍的改善作用,用火焰原子吸收分光光度法测定血锌(Zn)、铜(Cu)、锰(Mn)等含量.结果显示,氯化铝可导致小鼠学习记忆障碍,且有降低血Zn、Cu含量的作用(P<0.05);纳络酮治疗有改善Al中毒小鼠学习记忆障碍的作用,同时也增加了血Zn、Cu的含量.     

人参茎叶中二醇组皂甙对小鼠学习记忆及铜、锌、锰含量的影响

采用跳台法、火焰原子吸收分光光度计法分别研究了人参茎叶中二醇组皂甙(PDS)对小鼠学习记忆和全血铜(Cu)、锌(Zn)、锰(Mn)微量元素含量的影响. 结果表明,不同给药剂量各实验组小鼠跳台错误次数明显低于对照组(P<0.01),潜伏期明显延长(P<0.01);各实验组全血Cu含量均高于对照组(P<0.01),而Zn含量没有变化(P>0.05),Mn含量随给药剂量增加而增高,提示PDS具有提高小鼠学习记忆作用,可能与Cu、Mn含量增高有关.     

Reduction of tumorigenicity by an interferon-γ-gene-transduced tumor on another syngeneic tumor in a murine model

To evaluate the effect of interferon-γ-genetransduced cells, DS mice were inoculated into their footpads with syngeneic mammary adenocarcinoma SC42 admixed with interferon-γ producing mammary adenocarcinoma SC115Kγ, which had been established by an interferon-γ-gene transduction in another syngeneic mammary adenocarcinoma SC115 using retroviral vectors. These mice rejected both tumor cells and developed resistance to subsequent challenges with either SC115 or SC42 cells inoculated into their opposite posterior footpads. These results thus indicate that systemic immunological memory to each of the independent tumor cell lines developed in these mice. Although the SC42 cells admixed with irradiated SC115Kγ cells were rejected by these mice, the SC42 cells admixed with irradiated SC115neoR, in which the neo-gene had been transduced, were observed to proliferate. Tumor rejection was reversed by an in vivo administration of anti-interferon-γ antibody, thus suggesting that locally produced interferon-γ plays an important role in tumor elimination and immunological memory induction. In conclusion, interferon-γ-gene-transduced tumor cells are therefore considered to have a therapeutic potential for other types of malignant tumor cell lines.     

Hypermnesia in unilateral neglect

Thirteen right brain-damaged patients who were found to neglect pictures presented on the left of a display were presented the same stimuli, intermixed with foils, in a yes-no recognition test. Fifty per cent of patients claimed to have already seen one or more of the previously neglected pictures. This demonstrates that visual information that fails to access consciousness in neglect patients does retain the ability to surface as explicit memory at a later stage.     

Hypothesized neural dynamics of working memory: several chunks might be marked simultaneously by harmonic frequencies within an octave band of brain waves

The capacity of working memory (WM) for up to about seven simple items holds true both for humans and other species, and may depend upon a common characteristic of mammalian brains. This paper develops the conjecture that each WM item is represented by a different brain wave frequency. The binding-by-synchrony hypothesis, now being widely investigated, holds that the attributes of a single cognitive element cohere because electroencephalogram (EEG) synchrony temporarily unifies their substrates, which are distributed among different brain regions. However, thought requires keeping active more than one cognitive element, or WM "chunk," at a time. If there is indeed a brain wave frequency code for cognitive item-representations that are copresent within the same volume of neural tissue, the simple mathematical relationships of harmonies could provide a basis for maintaining distinctness and for orderly changes. Thus, a basic aspect of music may provide a model for an essential characteristic of WM. Music is a communicative phenomenon of "intermediate complexity," more highly organized than the firing patterns of individual neurons but simpler than language. If there is a distinct level of neural processing within which the microscopic physiological activity of neurons self-organizes into the macroscopic psychology of the organism, it might require such moderate complexity. Some of the obvious properties of music--orderly mixing and transitions among limited numbers of signal lines-are suggestive of properties that a dynamic neural process might need in order to organize and reorganize WM markers, but there are a number of additional, nonobvious advantageous properties of summating sinusoids in music-like relationships. In particular, harmonies register a stable periodic signal in the briefest possible time. Thus, the regularity of summating sinusoids whose frequencies bear harmony ratios suggests a particular kind of tradeoff between parallel and serial processing. When there are few copresent waves, at EEG frequencies, this sort of parallel coding retains behaviorally meaningful brief periods. A necessary companion hypothesis is that the brain wave frequencies underlying WM are confined to a single octave; that is, the upper and lower bounds of the band are in the ratio of 2:1. This hypothesized restriction, suggested by an empirical property of EEG bands that has been widely reported but rarely commented upon, has the important property of precluding spurious difference rhythms. A restriction to an octave, of "harmonious" frequency-markers for WM items, also seems consistent with a great deal of behavioral data suggesting that WM comprises a rapidly fading trace process in which only up to three or four item-representations are strongly activated simultaneously. There is also an additional, sequential renewal-or-revision process, within which up to another three or four items are being actively refreshed by rehearsal or replaced. Such serial processing may involve a less stringent octave band crowding problem.     

Early postnatal treatment with peptide preparations influences spatial navigation of young and adult rats

The brain derived peptidergic drug Cerebrolysin has been found to support the survival of neurons in vitro and in vivo. Positive effects on learning and memory have been demonstrated in various animal models and also in clinical trials. In the present study the effects of early postnatal administration of Cerebrolysin (Cere, 10 mg/ml peptides) or an enriched peptide fraction of Cere (E021, 80.6 mg/ml peptides) were investigated in young, young adult, and old adult rats. Rat pups received the drugs or saline for control on postnatal days 1–7. The animals were tested in the Morris water maze (MWM) either in the 5th week, in the 3rd or the 16th month of life for 6 consecutive days (test days 1–6), eight trials per day. In order to prevent the chance finding of the hidden platform, the rigid underwater platform was replaced by a collapsible island, resting at the bottom of the pool. The platform was raised when the animal stayed in the target area for 2 s. In the young and young adult rats both Cere and E021 treated rats showed shorter escape latencies than saline treated controls on all 6 test days. No significant differences in the swimming speed were evaluated for the young rats, although in 3-month-old drug-tested animals a moderate increase of the swimming speed was investigated. For 16-month-old animals no significant differences in either escape latencies or swimming speed was found. Summarizing, early postnatal application of Cere or E021 improved the spatial learning and memory of young rats and led to long-lasting behavioural effects at least up to 3 months after treatment.     

Control of resolution and perception in working memory

Mechanisms underlying and controlling resolution and perception in working memory are studied by means of a pulse-coupled network model. It is shown that the adaptivity, i.e. the degree to which previous activity affects the ability to fire, of the excitatory units can control several aspects of the network dynamics in a coordinated way to enable multiple items to be resolved and perceived in working memory. One basic aspect is the complexity of the dynamics that regulates the temporal resolution of several items. The slow NMDA-receptor-mediated component of synaptic couplings to excitatory units facilitates successive activations of a given item. The dimension of the activated subspace of the complete available neural representation space is gradually decreased as adaptivity is reduced. It is also shown that the formation of perception by sufficiently intense and coherent activation of different features of an object can be controlled concurrently with resolution by the adaptivity. The mechanisms derived can account for the observed capacity of working memory with respect to number of items consciously resolved and also for the observed temporal separation of different items. Numerous observations link neuromodulators to cognitive functions and to various brain disorders involving working memory. Based on the influence of various neuromodulators on neuronal adaptivity, the model can also account for neuromodulatory regulation of working memory functions.     

Regional brain activity during shape recognition impaired by a scopolamine challenge to encoding

In the present positron emission tomography (PET) study, we examine the effect of a scopolamine-induced challenge to encoding upon the pattern of regional cerebral blood flow during recognition of a list of abstract visual shapes 3 days after encoding of these shapes. This study was conducted to test hypotheses concerning the fusiform and thalamic contributions to object recognition arising from a previous imaging study of impaired recognition. In that study, we demonstrated that activity in the fusiform cortex and the thalamus during shape recognition was modulated by memory challenges. These memory challenges included, on one hand, impaired storage as a consequence of diazepam administration during encoding, and, on the other hand, impaired retrieval caused by a perceptual challenge. Activation in the fusiform cortex decreased during impaired recognition, irrespective of the type of challenge. In contrast, thalamic activation increased only when the recognition deficit resulted from impaired memory storage. Based on these results, we hypothesized that fusiform activation during recognition reflects the matching of an incoming stimulus with a stored one, whereas thalamic activation reflects retrieval attempts. These hypotheses would receive considerable support if scopolamine, which also impairs memory storage, induced similar modulations of fusiform and thalamic activation. In the present study, we observed that a scopolamine challenge to encoding does indeed modulate the activity in the very same regions that were previously modulated by a diazepam challenge. Hence, a similar memory deficit, although primarily effected through different neurochemical pathways, was paralleled by a similar modulation of activity in the same set of nodes in the shape recognition network. In the fusiform cortex, scopolamine decreased recognition-related activity, as did the sensory challenge of retrieval. Furthermore, covariate analysis demonstrated that the level of fusiform activity linearly correlates with behavioural performance. In the thalamus, activation increased following impaired encoding. This is in accordance with the idea that enhanced thalamic activity reflects increased effort expended in retrieval. In addition, in the intraparietal sulcus, differential activation also increased following impaired memory storage, possibly reflecting enhanced visuospatial attention in an effort to compensate for impaired performance.     

Perirhinal cortex input to the hippocampus in the rat: evidence for parallel pathways, both direct and indirect. A combined physiological and anatomical study

The possibility of a direct projection from the perirhinal cortex (PER) to areas CA1 and subiculum (SUB) in the hippocampus has been suggested on the basis of tracer studies, but this projection has not unequivocally been supported by physiological studies. The demonstration of such a functional pathway might be important to understand the functioning of the hippocampal memory system. Here we present physiological and further anatomical evidence for such a connection between PER and the hippocampus. Electrical stimulation of PER in vivo evoked field potentials (EFPs) at the border area of CA1/SUB, consisting of a short latency and a longer latency component. Current source density analysis revealed that the sink of the short latency component was situated in the molecular layer of area CA1/SUB, while the longer latency component had its sink in the outer molecular layer of the dentate gyrus (DG). Anterograde tracer injections in PER showed labelled fibres in the border area of CA1/SUB, but anatomical evidence for a projection of PER to DG was not found. When synaptic transmission in the entorhinal cortex was partly blocked, the amplitude of the longer latency component of the recorded EFPs in the hippocampus was decreased while the short latency component was not affected, which suggests that the indirect pathway originating in PER is mediated through a synaptic relay in the entorhinal cortex. From the present results we conclude that information originating in PER reaches area CA1/SUB by parallel, direct and indirect, routes. The existence of this parallel organization appears to form an essential feature for the proper function of the medial temporal lobe memory system.     

神经元烟碱乙酰胆碱受体受阻滞所致早老型痴呆动物模型的建立

海马区内注射Ｋ－银环蛇毒素（Ｋ－ＢＧＴ）可造成小鼠学习记忆明显障碍,以建立早老性痴呆（ＡＤ）患者学习记忆缺损模型。对小鼠的损害作用随Ｋ－ＢＧＴ剂量增加而明显增加。水迷宫多项指标测试结果表明,Ｋ－ＢＧＴ损害组小鼠与对照组小鼠相比,空间学习和记忆能力显著下降。明暗回避反应实验结果也表明,Ｋ－ＢＧＴ损害小鼠潜伏期明显缩短,错误次数增多;两种检测方法均表明Ｋ－ＢＧＴ可导致小鼠学习记忆明显障碍,而且这种损害具有持久的作用。