Effect of Dehydroepiandrosterone on Avoidance Behavior of Adult Male Rats

We studied the effect of repeated intraperitoneal treatment with dehydroepiandrosterone in doses of 0.1 and 0.7 mg/kg on conditioned-response activity and behavior of adult male rats. The effect of dehydroepiandrosterone on learning was estimated in conditioned active and passive avoidance response paradigms. Chronic administration of dehydroepiandrosterone in low and high doses had no effect on retention of conditioned passive avoidance response in adult male rats 24 h after learning. However, chronic administration of dehydroepiandrosterone in low dose impaired acquisition of the conditioned active avoidance response. It should be emphasized that chronic administration of dehydroepiandrosterone in high dose did not modulate acquisition and retention of this reaction.     

P300 and Long-Term Memory: Latency Predicts Recognition Performance

The study-test paradigm was used to investigate memory acquisition processes and the effects of repetition on long-term recognition memory. In this procedure, subjects are presented with a list of words (“targets”) to be memorized (Study series). They are later tested for recognition on a word list comprised of the target words mixed randomly with an equal number of new, distractor words (Test series). Both reaction time and the P300 component of the event-related brain potential were used as measures of processing time. During the Study series, large P300s were elicited despite a word category probability of 1.0. When the words from the Study series were divided on the basis of recognition performance, words that were subsequently recognized elicited P300s with shorter latencies than unrecognized words. P300 amplitude to words in the Study series increased with repetition while maintaining a constant latency. During the Test series, P300 latency and reaction time decreased with repetition for both target and distractor words. P300 amplitude to all words increased substantially over Test repetitions with target words eliciting larger P300s than distractor words. Words that were recognized more consistently during the Test series elicited larger and earlier P300s than words that were recognized less consistently. The P300 amplitude and latency results from both the Study and Test series are interpreted as reflecting the increased discriminability of the target words as the memory trace increases in strength.     

Editorial: Genetics of Brain Function and Cognition

There is overwhelming evidence for the existence of substantial genetic influences on individual differences in general and specific cognitive abilities, especially in adults. The actual localization and identification of genes underlying variation in cognitive abilities and intelligence has only just started, however. Successes are currently limited to neurological mutations with rather severe cognitive effects. The current approaches to trace genes responsible for variation in the normal ranges of cognitive ability consist of large scale linkage and association studies. These are hampered by the usual problems of low statistical power to detect quantitative trait loci (QTLs) of small effect. One strategy to boost the power of genomic searches is to employ endophenotypes of cognition derived from the booming field of cognitive neuroscienceThis special issue of Behavior Genetics reports on one of the first genome-wide association studies for general IQ. A second paper summarizes candidate genes for cognition, based on animal studies. A series of papers then introduces two additional levels of analysis in the black box between genes and cognitive ability: (1) behavioral measures of information-processing speed (inspection time, reaction time, rapid naming) and working memory capacity (performance on on single or dual tasks of verbal and spatio-visual working memory), and (2) electrophyiosological derived measures of brain function (e.g., event-related potentials). The obvious way to assess the reliability and validity of these endophenotypes and their usefulness in the search for cognitive ability genes is through the examination of their genetic architecture in twin family studies. Papers in this special issue show that much of the association between intelligence and speed-of-information processing/brain function is due to a common gene or set of genes, and thereby demonstrate the usefulness of considering these measures in gene-hunting studies for IQ.     

孕鼠被动吸烟对子代学习记忆功能及海马神经生长因子含量的影响

目的 探讨孕鼠被动吸烟对子代学习记忆功能的影响及其机制。方法 采用反映学习记忆功能的水迷宫法测试大鼠神经行为的改变，IRMA法测定大鼠海马神经生长因子的含量变化。结果 孕期被动吸烟使仔鼠学习记忆能力下降，海马神经生长因子含量明显降低。结论 孕期被动吸烟降低仔鼠学习记忆功能与海马神经生长因子代谢的失调有关。     

Dissecting the complexity of the memory T cell response

Memory immune responses are classically attributed to the reactivation of long-lived, antigen-specific T lymphocytes that persist in a quiescent state. Determining mechanisms for the generation of memory T cells and dissecting the functional nature of the memory T cell pool has been encumbered by an inability to distinguish recently activated effector T cells from memory T cells. We have established new activation and biochemical criteria that distinguish effector and memory T cells and have applied these criteria to follow memory generation from activated cells in vivo. We found that the resultant memory T cell pool is heterogeneous and consists of effector-like and resting memory-like subsets that differ in expression of the homing receptor, CD62L. We discuss these findings in the context of memory T cell heterogeneity identified in human and mouse systems. These results suggest that more than one type of previously activated T cell can mediate recall or memory immune responses and that elucidating the fundamental phenotypic and functional features of memory T cell subsets is therefore critical to deciphering the complex nature of the memory immune response.     

Interaction of sensory and cognitive processes during visual recognition: The role of the associative areas of the cerebral cortex

The first part of the present study used a model of Alzheimers disease in two groups of animals (three monkeys in each), given injections of neurotoxins (monkeys of group I) and physiological saline (monkeys of group II). Before injections, all monkeys were trained to discriminate stimuli containing different types of information (spatial frequency grids and geometrical figures of different colors and with different spatial relationships between objects) and to perform spatial selection. The dynamics of impairments in the characteristics of working memory were identified using delayed differentiation tasks in monkeys of both groups before injections and every two months after injections. Quantitative measures of impairments were made using the entropy of visual recognition, which characterizes uncertainty in decision-taking. The development of Alzheimers disease in rhesus macaques was characterized by a deficit of working memory, resulting from lesions to the two component processes of memory. Impairments of the first of these in monkeys of group I were manifest as a significant increase in entropy, which is associated with correct decision-taking. The magnitude of the increase depended on the type of visual information. Impairments of the second component were characterized by increases in entropy associated with refusals to take decisions and were independent of the delay duration and the type of visual information. Monkeys given injections of physiological saline showed no significant changes in these characteristics. The features of working memory were also studied in the second part of the investigation, using four groups of Rhesus macaques: intact, those with bilateral extirpation of the sulcus principalis or field 7 or both: degradation again identified two components. Entropy associated with this was increased significantly for most of the stimuli tested on monkeys of all extirpation groups as compared with intact animals. Significant differences were found in these characteristics for a number of stimuli, which depended on the location of the structures removed. The characteristics of impairments of the components of working memory resulting in the development of Alzheimers disease showed that the cholinergic mechanisms responsible for sensory processing differ from those involved in decision-taking. The structural-functional organization of the interaction of sensory and cognitive processes controlled by the motivation and attention systems is discussed, as is the role of the associative areas of the cortex.Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 89, No. 10, pp. 1226–1239, October, 2003.     

Lesion of posterior parietal cortex in rats does not disrupt place avoidance based on either distal or proximal orienting cues

A current topic in neurobiology is the study of the role of various brain structures in processing of spatial information. The present study was aimed at elucidating the role of the rat posterior parietal cortex in performing a place avoidance task. Two variants of the task were used: an arena frame task, in which animals were trained to avoid a sector defined by local cues bound to the surface of a rotating arena, and the room frame task, in which the shock sector was defined with respect to distal room landmarks. The results showed that both control and lesioned rats were able to efficiently solve both tasks, while locomotion was not altered. These results suggest that the posterior parietal cortex is not crucial for the processing of either proximal or distal cues in place avoidance.     

Learning and memory impairment in adult rats due to severe zinc deficiency during lactation

In a series of three experiments, adult rats who suffered severe zinc deficiency and/or undernutrition during lactation were tested in a 17-arm radial maze for working memory, reference memory, forgetting and learning. In Experiment 1, eight out of 17 arms were baited. The zinc deficient (ZD) and undernourished (PF) rats revealed a learning deficit when compared to adequately nourished rats (AL). ZD rats also appeared to display a loss of working memory. No evidence of loss of reference memory was observed among any of the groups. A reverse learning procedure was used in Experiment 2 to test the same rats used in Experiment 1. ZD rats were significantly inferior in performance of the reverse learning task compared to the AL and PF rats. No significant differences in performance were noted between the AL and PF rats. Although all groups displayed forgetfulness from Experiment 1 to Experiment 2, no significant differences in forgetfulness were evidenced among the groups. In Experiment 3, all 17 arms were baited. The ZD rats displayed a significant working memory deficit as compared to the AL and PF rats. No significant differences in working memory between the AL and PF rats occurred. The possibility that the differences in performance were due to differences in food motivation or attention was considered and rejected. It was concluded that ZD rats experienced a severe learning deficit and some working memory deficit while the PF rats experienced a mild learning deficit as compared to the AL rats.     

Intrahippocampal cholinergic grafts in aged rats compensate impairments in a radial maze and in a place learning task

Summary Age-related cognitive impairments were studied in rats kept in semi-enriched conditions during their whole life, and tested during ontogeny and adult life in various classical spatial tasks. In addition, the effect of intrahippocampal grafts of fetal septal-diagonal band tissue, rich in cholinergic neurons, was studied in some of these subjects. The rats received bilateral cell suspensions when aged 23–24 months. Starting 4 weeks after grafting, they were trained during 5 weeks in an 8-arm maze made of connected plexiglass tunnels. No age-related impairment was detected during the first eight trials, when the maze shape was that of a classical radial maze in which the rats had already been trained when young. The older rats were impaired when the task was made more difficult by rendering two arms parallel to each other. They developed an important neglect of one of the parallel tunnels resulting in a high amount of errors before completion of the task. In addition, the old rats developed a systematic response pattern of visits to adjacent arms in a sequence, which was not observed in the younger subjects. None of these behaviours were observed in the old rats with a septal transplant. Sixteen weeks after grafting, another experiment was conducted in a homing hole board task. Rats were allowed to escape from a large circular arena through one hole out of many, and to reach home via a flexible tube under the table. The escape hole was at a fixed position according to distant room cues, and olfactory cues were made irrelevant by rotating the table between the trials. An additional cue was placed on the escape position. No age-related difference in escape was observed during training. During a probe trial with no hole connected and no proximal cue present, the old untreated rats were less clearly focussed on the training sector than were either the younger or the grafted old subjects. Taken together, these experiments indicate that enriched housing conditions and spatial training during adult life do not protect against all age-related deterioration in spatial ability. However, it might be that the considerable improvement observed in the grafted subjects results from an interaction between the graft treatment and the housing conditions.     

DNA vaccine encoding human immunodeficiency virus-1 Gag, targeted to the major histocompatibility complex II compartment by lysosomal-associated membrane protein, elicits enhanced long-term memory response

Antigen presentation by major histocompatibility complex type II (MHC II) molecules and activation of CD4+ helper T cells are critical for the generation of immunological memory. We previously described a DNA vaccine encoding human immunodeficiency virus-1 p55Gag as a chimera with the lysosome-associated membrane protein (LAMP/gag). The LAMP/gag chimera protein traffics to the MHC II compartment of transfected cells and elicits enhanced immune responses as compared to a DNA vaccine encoding native gag not targeted to the MHC II compartment. We have now investigated the long-term responses of immunized mice and show that the LAMP/gag DNA vaccine promotes long-lasting B cell- and CD4+ and CD8+ T-cell memory responses induced by DNA encoding non-targeted Gag decay rapidly and elicit very low or undetectable levels of gag DNA is sufficient to generate T-cell memory. Following this initial priming immunization with LAMP/gag DNA, booster immunizations with native gag DNA or the LAMP/gag chimera are equally efficient in eliciting B- and T-cell secondary responses, results in accordance with observations that secondary expansion of CD8+ cells in the boost phase does not require additional CD4+ help. These findings underscore the significance of targeting DNA-encoded vaccine antigens to the MHC II processing compartments for induction of long-term immunological memory.