Ceftriaxone rescues hippocampal neurons from excitotoxicity and enhances memory retrieval in chronic hypobaric hypoxia

Exposure to high altitude is known to cause impairment in cognitive functions in sojourners. The molecular events leading to this behavioral manifestation, however, still remain an enigma. The present study aims at exploring the nature of memory impairment occurring on chronic exposure to hypobaric hypoxia and the possible role of glutamate in mediating it. Increased ionotropic receptor stimulation by glutamate under hypobaric hypoxic conditions could lead to calcium mediated excitotoxic cell death resulting in impaired cognitive functions. Since glutamate is cleared from the synapse by the Glial Glutamate Transporter, upregulation of the transporter can be a good strategy in preventing excitotoxic cell death. Considering previous reports on upregulation of the expression of Glial Glutamate Transporter on ceftriaxone administration, the therapeutic potential of ceftriaxone in ameliorating hypobaric hypoxia induced memory impairment was investigated in male Sprague Dawley rats. Exposure to hypobaric hypoxia equivalent to an altitude of 7600 m for 14 days lead to oxidative stress, chromatin condensation and neuronal degeneration in the hippocampus. This was accompanied by delayed memory retrieval as evident from increased latency and pathlength in Morris Water Maze. Administration of ceftriaxone at a dose of 200 mg/kg for 7 days and 14 days during the exposure on the other hand improved the performance of rats in the water maze along with decreased oxidative stress and enhanced neuronal survival when compared to hypoxic group without drug administration. An increased expression of Glial Glutamate Transporter was also observed following drug administration indicating faster clearance of glutamate from the synapse. The present study not only brings to light the effect of longer duration of exposure to hypobaric hypoxia on the memory functions, but also indicates the pivotal role played by glutamate in mediating excitotoxic neuronal degeneration at high altitude. The therapeutic potential of ceftriaxone in providing neuroprotection in excitotoxic conditions by increasing Glial Glutamate Transporter expression and thereby enhancing glutamate uptake from the synapse has also been explored.     

Rigidity in social and emotional memory in the R6/2 mouse model of Huntington's disease

Four experiments were conducted to examine social and emotional memory in the R6/2 transgenic mouse model of Huntington’s disease. First, R6/2 mice were tested in a social transmission of food preference task where they had to acquire a preference for a flavoured food (acquisition) and subsequently to learn a preference for a different flavour (shifted reinforcement). R6/2 mice performed well in the acquisition trial. However, they were impaired in the shifted reinforcement trial and perseverated on the first preference learned. Second, mice were trained in an inhibitory avoidance paradigm, with either one or two footshocks delivered during the training. WT mice given one footshock showed retention levels lower than those of mice trained with two footshocks. By contrast, there was no difference in retention levels of R6/2 mice given either one or two footshocks. Third, mice were tested in an active avoidance task that paired a mild footshock with a warning light. R6/2 mice had a strong age-dependent deficit in this task. Finally, mice were tested in a conditioned taste aversion task that paired a saccharine solution with a nausea-inducing agent (LiCl). R6/2 mice displayed normal aversion, however this was not extinguished following repeated exposure to saccharine solution alone. Our data show that while R6/2 mice have functional hippocampus-based memory, they have deficits in striatum-based memory skills. Further, social and emotional memories appear to be encoded in a rigid way that is not influenced by subsequent learning or by arousal levels.     

Appetitive memory reconsolidation depends upon NMDA receptor-mediated neurotransmission

Memory persistence is a dynamic process involving the reconsolidation of memories after their reactivation. Reconsolidation impairments have been demonstrated for many types of memories in rats, and signaling at N-methyl-d-aspartate (NMDA) receptors appears often to be a critical pharmacological mechanism. Here we investigated the reconsolidation of appetitive pavlovian memories reinforced by natural rewards. In male Lister Hooded rats, systemic administration of the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-SH-dibenzo{a,d}cyclohepten-5,10-imine maleate (MK-801, 0.1 mg/kg i.p.) either before or immediately following a brief memory reactivation session abolished the subsequent acquisition of a new instrumental response with sucrose conditioned reinforcement. However, only when injected prior to memory reactivation was MK-801 effective in disrupting the maintenance of a previously-acquired instrumental response with conditioned reinforcement. These results demonstrate that NMDA receptor-mediated signaling is required for appetitive pavlovian memory reconsolidation.     

Differential effects of beta-adrenergic receptor blockade in basolateral amygdala or insular cortex on incidental and associative taste learning

The importance of central β-adrenergic system has been essentially investigated in aversive/emotional learning tasks. However, recent data suggest that the β-adrenergic system is also required for incidental taste learning. In the present study we evaluated in rats whether β-adrenergic receptor activity is required for taste habituation, an incidental taste learning, and also for conditioned taste aversion (CTA) learning, an associative learning. To address this issue, a low dose of the β-adrenergic antagonist propranolol was infused before learning in either the basolateral amygdala (BLA) or the insular cortex (IC), two forebrain areas reported to play a key role in taste memory formation. Incidental taste learning was assessed using a single presentation of the sweet taste saccharin 0.1%, which is sufficient to increase saccharin consumption (relative to water baseline) during a second presentation. CTA was assessed by pairing the first saccharin 0.1% presentation with a delayed gastric malaise, thus causing a decrease in saccharin consumption (relative to water baseline) during a second presentation. Propranolol infusion in BLA (1 μg/0.2μl) or IC (2.5 μg/0.5 μl) before the first taste exposure impaired incidental taste learning but did not affect CTA. These results highlight the important role played by the β-adrenergic receptor activation in cortical and amygdaloid structures during taste learning. Moreover, they are the first to suggest that incidental learning is more sensitive to blockade of noradrenergic system than associative learning.     

Asymmetrical retention functions for sequences of light flashes or tone bursts in the rat

In Experiment 1, rats were trained in a symbolic delayed matching-to-sample task to discriminate sample stimuli that consisted of sequences of magazine light flashes. The intertrial interval was illuminated by the houselight for Group Light, and it was dark for Group Dark. Retention functions exhibited a choose-many response bias when the delay interval was illuminated by the houselight in both groups, and no consistent response bias when the delay interval was dark. In Experiment 2, rats were trained to discriminate sample stimuli that consisted of sequences of tone bursts. During delay testing, a different tone (i.e., different frequency and location than the sample tone) was present or absent during the delay interval. The retention functions exhibited a significant choose-many bias when tone was present during the delay and a choose-few bias when tone was absent. Asymmetrical retention functions for tone burst and light flash sequences are due to the similarity between the stimulus conditions of the delay interval and the modality of the sequential event being discriminated. These results are consistent with an instructional ambiguity explanation of response biases in memory for number.     

记忆中"曾经"的承诺

该文关注“曾经”与“承诺”—“复仇”与“拯救”如何相关特别是如何转换的“记忆的政治”。问题的背景是苦难:作为存在论或现象着的生活世界的基本事实,它是人类唯一可以普遍面对神、面对政治的“救赎地”,而不是“弥撒”中可以流逝的将来时,或在“复仇”中永远走不出的过去时。这里重要的是记忆形式的时间结构发生了根本的变化。因而“曾经”不是无生命力的过去压力(如尼采所批判的和本雅明所清理的);也不是简单转化为复仇的有生命力的权力意志即强权政治(如尼采所一厢情愿的);而是走出复仇的拯救———即走出过去时的———“记忆”中的“曾经”的“承诺”。但事实上,它已不能由西方文化的特质独立承担了。     

Differences in Fear of Isolation as an explanation of Cultural Differences: Evidence from memory and reasoning

Previous research suggests that members of East Asian cultures show a greater preference for dialectical thinking and sensitivity to context information than do Westerners. We suggest this difference is rooted in a greater chronic Fear of Isolation (FOI) in East Asians than in Westerners. To support this hypothesis, we manipulated FOI in a group of Westerners and assessed their relative preference for dialectical proverbs and sensitivity to context. For cross-cultural validation of our hypothesis, we assessed the relationship between chronic levels of FOI and dialectical reasoning in Koreans. Consistent with our proposal, both experimentally primed FOI (Experiment 1A and 2) and chronic levels of FOI (Experiment 1B) were positively related to relative preference for dialectical proverbs. This effect was independent of participants’ level of negative mood (Experiment 2). A third experiment showed that sensitivity to context was affected by FOI in a manner consistent with previous studies of cultural differences (Experiment 3).     

学习困难儿童在工作记忆任务中抑制机制的研究

本研究的目的旨在探讨在WM任务中,LD儿童是否存在抑制机制缺陷。实验程序采用重复启动范式,设计“预期”和“目标”两种启动条件,随后通过间接测量的方式(内隐记忆测验)分别测得LD儿童和NLD儿童对预期词和目标词的启动量。结果表明,LD儿童对预期词的启动分数与目标词没有显著差异,NLD儿童对目标词的启动分数显著高于对预期词的启动分数。我们得出结论:在工作记忆任务中,LD儿童存在抑制机制缺陷。     

Individual differences in information order effects: The importance of right-hemisphere access in belief updating

The order in which information is received alters the evaluation of causal hypotheses. Specifically, research suggests that the last piece of information oftentimes has the greatest impact on the evaluation and that the difference in subjective value between two pieces of information is an important factor influencing the magnitude of this recency effect. The present paper extends this line of work by exploring individual differences in this phenomenon via one's degree of handedness. Two hundred and five participants were given two hypothetical scenarios and related causal hypotheses accompanied by two pieces of additional information and asked to revise their belief in each hypothesis as information accumulated. Results confirmed predictions that 1) inconsistent/mixed-handers (those who use their non-dominant hand for at least some activities) show a larger effect with two pieces of inconsistent weak or strong information, and 2) neither mixed-handers nor consistent/strong-handers (those who use their dominant hand for almost all activities) show an effect with strong and weak pieces of consistent information. Mixed-handers' susceptibility to persuasive arguments and Ramachandran’s (1995; Ramachandran and Blakeslee, 1998) belief-updating theory centered around communication between the two halves of the brain and functional access to the right hemisphere are used to account for these data.     

Aging and strategic retrieval in a cued-recall test: the role of executive functions and fluid intelligence

Cued-recall in episodic memory was investigated in relation to low and high cognitive support at retrieval, executive function level and fluid intelligence level in 81 healthy adults divided first into two age groups (young and elderly adults). The first analyses showed that age-related differences were greater when a low cognitive support was provided to recall the words. An individual index of loss of performance when the number of cues was decreased was then calculated. Hierarchical regression analysis revealed that the executive functions measure (perseverative errors on the Wisconsin Card Sorting Test) was a better candidate than the fluid intelligence measure (Cattell's culture fair test) to account for the age-related variance of the size of performance loss. These findings suggest that age differences in implementing strategic retrieval may be mainly due to a decline in executive functions.