一氧化氮对谷氨酸单钠脑损害小鼠学习记忆能力的影响

目的　观察谷氨酸单钠 (MSG)对小鼠学习记忆的影响及血浆、脑内NO含量的变化。方法　给断乳分窝小鼠MSG灌胃 ,每天 2次 ,连续 30d ,31d早灌胃后对小鼠进行迷宫行为训练 ,2 4h后对其进行迷宫记忆检测 ,用硝酸还原酶法检测血浆脑内的NO含量。结果　MSG对小鼠学习记忆能力有影响并存在剂量效应关系 ,其血浆、脑中NO含量均升高并有显著差异 (P <0 .0 5 )。结论　NO可加重MSG对小鼠学习与记忆的损害作用。     

Effects of priming duration on retention over the first 1 1/2 years of life

Exposing individuals to an isolated component (a prime) of a prior event alleviates its forgetting. Two experiments with 120 human infants between 3 and 18 months of age determined the minimum duration of a prime that can reactivate a forgotten memory and how long the reactivated memory persists. Infants learned an operant task, forgot it, were exposed to the prime, and later were tested for renewed retention. In Experiment 1, the minimum duration of an effective prime decreased logarithmically with age, but was always longer than the duration of a mere glance. In Experiment 2, the reactivated memory was forgotten twice as fast after a minimum-duration prime as after a full-length one, irrespective of priming delay and infant age. These data reveal that the minimum effective prime duration psychophysically equates the accessibility of forgotten memories. We conclude that priming is perceptually based with effects that are organized on a ratio (log) scale.     

Immunization with excretory-secretory molecules of intestinal nematodes induces antigen-specific protective memory Th2 cell responses

Parasitic nematodes infect more than 1 billion people in the global south. The development of effective antihelminthic vaccines is a crucial tool for their future elimination. Protective immune responses to nematodes depend on Gata3⁺ Th2 cells, which can also be induced by nematode-released products. Whether these nematode products induce antigen-specific long-lived memory T cells and thereby confer protection against a challenge infection is not known yet. Hence, we set out to characterize the formation of memory Th2 cells induced by immunization with Heligmosomoides polygyrus excretory-secretory (HES) products, infection-induced versus immunization-induced recall responses to a challenge infection, and whether HES-induced memory T cells show protective properties following adoptive transfer. Our results show that 8 weeks postimmunization, HES induces long-lived functional memory Th2 cells at the site of immunization in the peritoneal cavity. Following a H. polygyrus challenge infection, HES-immunized mice display MHC-II-dependent antigen-specific Th2 cytokine responses in the gut-draining lymph nodes, comparable to those induced by a prior natural infection. Moreover, adoptive transfer of sorted memory CD4⁺ T cells from HES-immunized donors reduces female worm fecundity following a challenge H. polygyrus infection in recipient mice, highlighting a protective role for immunization-induced memory T cells.     

Lymphocytes infiltrating the CNS during inflammation display a distinctive phenotype and bind to VCAM-1 but not to MAdCAM-1

The nature of inflammatory lymphocytes recruited to the CNShas been studied in a model of chronic inflammation. Injectionof killed Corynebacterlum parvum into the cortex of the mousebrain produces a circumscribed inflammatory cellular infiltratearound the injection site, and recruited mononuclear inflammatorycells (IC) can be isolated for flow cytometric analysis. Themajority of IC were T cells. In comparison with the predominantnaive population of mesenteric lymph node T cells, IC T cellsexpress much higher levels of CD44, LFA-1 and ICAM-1, and lowerlevels of CD45RB, features commonly associated with memory (previouslyactivated) cells. In addition, in contrast to the L-selectin⁺6-integrin^low phenotype of naive lymph node T cells, IC T cellslacked L-selectin and were 6-integrin^–. Mac-1, recentlyproposed as another marker of memory T cell differentation,was not displayed by IC T cells, suggesting that Mac-1 expressionmay be heterogeneous among memory T cell subsets. A subset ofmesenteric lymph node (MLN) T cells, probably representing activatedT cells undergoing the naive to memory transition, but not ofIC T cells, expressed high levels of 6-, ß7- and E-integrin.IC and MLN naive T cells expressed comparable levels of 4-integrin,but IC T cells stain poorly with anti-ß7 mAbs andwith mAb DATK 32, specific for the 4ß7 heterodimericlymphocyte homing receptor for the mucosal addressin MAdCAM-1,suggesting that these inflammatory cells express more 4ß1than 4ß7. Consistent with this, in in vitro adhesionassays, brain IC bound better than MLN cells to the 4ß1integrin ligand VCAM-1 and the LFA-1 ligand ICAM-1 but adheredvery poorly to the 4ß7 ligand MAdCAM-1. These findingsare consistent with and extend previous immunohistological studiesof T cells in murine experimental autoimmune encephalomyelitis,and demonstrate a distinctive phenotype for lymphocytes beingpresent in the chronically inflamed brain.     

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.