Discovery of genes involved with learning and memory: An experimental synthesis of Hirschian and Benzerian perspectives

The biological bases of learning and memory are being revealed today with a wide array of molecular approaches, most of which entail the analysis of dysfunction produced by gene disruptions. This perspective derives both from early “genetic dissections” of learning in mutant Drosophila by Seymour Benzer and colleagues and from earlier behavior-genetic analyses of learning and in Diptera by Jerry Hirsch and coworkers. Three quantitative-genetic insights derived from these latter studies serve as guiding principles for the former. First, interacting polygenes underlie complex traits. Consequently, learning/memory defects associated with single-gene mutants can be quantified accurately only in equilibrated, heterogeneous genetic backgrounds. Second, complex behavioral responses will be composed of genetically distinct functional components. Thus, genetic dissection of complex traits into specific biobehavioral properties is likely. Finally, disruptions of genes involved with learning/memory are likely to have pleiotropic effects. As a result, task-relevant sensorimotor responses required for normal learning must be assessed carefully to interpret performance in learning/memory experiments. In addition, more specific conclusions will be obtained from reverse-genetic experiments, in which gene disruptions are restricted in time and/or space.

Memory from the dynamics of intrinsic membrane currents

Almost all theoretical and experimental studies of the mechanisms underlying learning and memory focus on synaptic efficacy and make the implicit assumption that changes in synaptic efficacy are both necessary and sufficient to account for learning and memory. However, network dynamics depends on the complex interaction between intrinsic membrane properties and synaptic strengths and time courses. Furthermore, neuronal activity itself modifies not only synaptic efficacy but also the intrinsic membrane properties of neurons. This paper presents examples demonstrating that neurons with complex temporal dynamics can provide short-term “memory” mechanisms that rely solely on intrinsic neuronal properties. Additionally, we discuss the potential role that activity may play in long-term modification of intrinsic neuronal properties. While not replacing synaptic plasticity as a powerful learning mechanism, these examples suggest that memory in networks results from an ongoing interplay between changes in synaptic efficacy and intrinsic membrane properties.

Studies of retrograde memory: A long-term view

Studies of retrograde amnesia are reviewed. First, the issues of temporal gradients of retrograde amnesia are discussed. Second, the question of the anatomical substrates of this syndrome are considered. Finally, some evidence for fractionation of different classes of memoranda within the retrograde time period are presented.

A neural system for human visual working memory

Working memory is the process of actively maintaining a representation of information for a brief period of time so that it is available for use. In monkeys, visual working memory involves the concerted activity of a distributed neural system, including posterior areas in visual cortex and anterior areas in prefrontal cortex. Within visual cortex, ventral stream areas are selectively involved in object vision, whereas dorsal stream areas are selectively involved in spatial vision. This domain specificity appears to extend forward into prefrontal cortex, with ventrolateral areas involved mainly in working memory for objects and dorsolateral areas involved mainly in working memory for spatial locations. The organization of this distributed neural system for working memory in monkeys appears to be conserved in humans, though some differences between the two species exist. In humans, as compared with monkeys, areas specialized for object vision in the ventral stream have a more inferior location in temporal cortex, whereas areas specialized for spatial vision in the dorsal stream have a more superior location in parietal cortex. Displacement of both sets of visual areas away from the posterior perisylvian cortex may be related to the emergence of language over the course of brain evolution. Whereas areas specialized for object working memory in humans and monkeys are similarly located in ventrolateral prefrontal cortex, those specialized for spatial working memory occupy a more superior and posterior location within dorsal prefrontal cortex in humans than in monkeys. As in posterior cortex, this displacement in frontal cortex also may be related to the emergence of new areas to serve distinctively human cognitive abilities.

Role of cortical N-methyl-D-aspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia.

Working memory refers to the ability of the brain to store and manipulate information over brief time periods, ranging from seconds to minutes. As opposed to long-term memory, which is critically dependent upon hippocampal processing, critical substrates for working memory are distributed in a modality-specific fashion throughout cortex. N-methyl-D-aspartate (NMDA) receptors play a crucial role in the initiation of long-term memory. Neurochemical mechanisms underlying the transient memory storage required for working memory, however, remain obscure. Auditory sensory memory, which refers to the ability of the brain to retain transient representations of the physical features (e.g., pitch) of simple auditory stimuli for periods of up to approximately 30 sec, represents one of the simplest components of the brain working memory system. Functioning of the auditory sensory memory system is indexed by the generation of a well-defined event-related potential, termed mismatch negativity (MMN). MMN can thus be used as an objective index of auditory sensory memory functioning and a probe for investigating underlying neurochemical mechanisms. Monkeys generate cortical activity in response to deviant stimuli that closely resembles human MMN. This study uses a combination of intracortical recording and pharmacological micromanipulations in awake monkeys to demonstrate that both competitive and noncompetitive NMDA antagonists block the generation of MMN without affecting prior obligatory activity in primary auditory cortex. These findings suggest that, on a neurophysiological level, MMN represents selective current flow through open, unblocked NMDA channels. Furthermore, they suggest a crucial role of cortical NMDA receptors in the assessment of stimulus familiarity/unfamiliarity, which is a key process underlying working memory performance.

Deficits in memory and hippocampal long-term potentiation in mice with reduced calbindin D28K expression.

The influx of calcium into the postsynaptic neuron is likely to be an important event in memory formation. Among the mechanisms that nerve cells may use to alter the time course or size of a spike of intracellular calcium are cytosolic calcium binding or "buffering" proteins. To consider the role in memory formation of one of these proteins, calbindin D28K, which is abundant in many neurons, including the CA1 pyramidal cells of the hippocampus, transgenic mice deficient in calbindin D28K have been created. These mice show selective impairments in spatial learning paradigms and fail to maintain long-term potentiation. These results suggest a role for calbindin D28K protein in temporally extending a neuronal calcium signal, allowing the activation of calcium-dependent intracellular signaling pathways underlying memory function.

The resource consumption principle: attention and memory in volumes of neural tissue.

In the cerebral cortex, the small volume of the extracellular space in relation to the volume enclosed by synapses suggests an important functional role for this relationship. It is well known that there are atoms and molecules in the extracellular space that are absolutely necessary for synapses to function (e.g., calcium). I propose here the hypothesis that the rapid shift of these atoms and molecules from extracellular to intrasynaptic compartments represents the consumption of a shared, limited resource available to local volumes of neural tissue. Such consumption results in a dramatic competition among synapses for resources necessary for their function. In this paper, I explore a theory in which this resource consumption plays a critical role in the way local volumes of neural tissue operate. On short time scales, this principle of resource consumption permits a tissue volume to choose those synapses that function in a particular context and thereby helps to integrate the many neural signals that impinge on a tissue volume at any given moment. On longer time scales, the same principle aids in the stable storage and recall of information. The theory provides one framework for understanding how cerebral cortical tissue volumes integrate, attend to, store, and recall information. In this account, the capacity of neural tissue to attend to stimuli is intimately tied to the way tissue volumes are organized at fine spatial scales.

Memory enhancement by intrahippocampal, intraamygdala, or intraentorhinal infusion of platelet-activating factor measured in an inhibitory avoidance task.

Platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), which is thought to be a retrograde messenger in long-term potentiation (LTP), enhances glutamate release and LTP through an action on presynaptic nerve endings. The PAF antagonist BN 52021 blocks CA1 LTP in hippocampal slices, and, when infused into rat dorsal hippocampus pre- or posttraining, blocks retention of inhibitory avoidance. Here we report that memory is affected by pre- or posttraining infusion of the PAF analog 1-O-hexadecyl-2-N-methylcarbamoyl-sn-glycerol-3-phosphocholine (mc-PAF) into either rat dorsal hippocampus, amygdala, or entorhinal cortex. Male Wistar rats were implanted bilaterally with cannulae in these brain regions. After recovery from surgery, the animals were trained in step-down inhibitory avoidance or in a spatial habituation task and tested for retention 24 h later. mc-PAF (1.0 microgram per side) enhanced retention test performance of the two tasks when infused into the hippocampus before training without altering training session performance. In addition, mc-PAF enhanced retention test performance of the avoidance task when infused into (i) the hippocampus 0 but not 60 min after training; (ii) the amygdala immediately after training; and (iii) the entorhinal cortex 100 but not 0 or 300 min after training. In confirmation of previous findings, BN 52021 (0.5 microgram per side) was found to be amnestic for the avoidance task when infused into the hippocampus or the amygdala immediately but not 30 or more minutes after training or into the entorhinal cortex 100 but not 0 or 300 min after training. These findings support the hypothesis that memory involves PAF-regulated events, possibly LTP, generated at the time of training in hippocampus and amygdala and 100 min later in the entorhinal cortex.

Lyra: uma função de derivação de chaves com custos de memória e processamento configuráveis.

Este documento apresenta o Lyra, um novo esquema de derivação de chaves, baseado em esponjas criptográficas. O Lyra foi projetado para ser estritamente sequencial, fornecendo um nível elevado de segurança mesmo contra atacantes que utilizem múltiplos núcleos de processamento, como uma GPU ou FPGA. Ao mesmo tempo possui uma implementação simples em software e permite ao usuário legítimo ajustar o uso de memória e tempo de processamento de acordo com o nível de segurança desejado. O Lyra é, então, comparado ao scrypt, mostrando que esta proposta fornece um nível se segurança mais alto, além de superar suas deficiências. Caso o atacante deseje realizar um ataque utilizando pouca memória, o tempo de processamento do Lyra cresce exponencialmente, enquanto no scrypt este crescimento é apenas quadrático. Além disto, para o mesmo tempo de processamento, o Lyra permite uma utilização maior de memória, quando comparado ao scrypt, aumentando o custo de ataques de força bruta.

Crypto at the Time of Surveillance: Sharing with the Cloud

These days as we are facing extremely powerful attacks on servers over the Internet (say, by the Advanced Persistent Threat attackers or by Surveillance by powerful adversary), Shamir has claimed that “Cryptography is Ineffective”and some understood it as “Cryptography is Dead!” In this talk I will discuss the implications on cryptographic systems design while facing such strong adversaries. Is crypto dead or we need to design it better, taking into account, mathematical constraints, but also systems vulnerability constraints. Can crypto be effective at all when your computer or your cloud is penetrated? What is lost and what can be saved? These are very basic issues at this point of time, when we are facing potential loss of privacy and security.

Role of Dopamine D2 Receptors in the Consolidation of Amphetamine-Cue Memory in Conditioned Activity in Rats

The neurotransmitter dopamine (DA) plays an essential role in reward-related incentive learning, whereby neutral stimuli gain the ability to elicit approach and other responses. In an incentive learning paradigm called conditioned activity, animals receive a stimulant drug in a specific environment over the course of several days. When then placed in that environment drug-free, they generally display a conditioned hyperactive response. Modulating DA transmission at different time points during the paradigm has been shown to disrupt or enhance conditioning effects. For instance, blocking DA D2 receptors before sessions generally impedes the acquisition of conditioned activity. To date, no studies have examined the role of D2 receptors in the consolidation phase of conditioned activity; this phase occurs immediately after acquisition and involves the stabilization of memories for long-term storage. To investigate this possible role, I trained Wistar rats (N = 108) in the conditioned activity paradigm produced by amphetamine (2.0 mg/kg, intraperitoneally) to examine the effects of the D2 antagonist haloperidol (doses 0.10, 0.25, 0.50, 0.75, 1.0, & 2.0 mg/kg, intraperitoneally) administered 5 min after conditioning sessions. Two positive control groups received haloperidol 1 h before conditioning sessions (doses 1.0 mg/kg and 2.0 mg/kg). The results revealed that post-session haloperidol at all doses tested did not disrupt the consolidation of conditioned activity, while pre-session haloperidol at 2.0 mg/kg prevented acquisition, with the 1.0 mg/kg group trending toward a block. Additionally, post-session haloperidol did not diminish activity during conditioning days, unlike pre-session haloperidol. One possible reason for these findings is that the consolidation phase may have begun earlier than when haloperidol was administered, since the conditioned activity paradigm uses longer learning sessions than those generally used in consolidation studies. Future studies may test if conditioned activity can be achieved with shorter sessions; if so, haloperidol would then be re-tested at an earlier time point. D2 receptor second messenger systems may also be investigated in consolidation. Since drug-related incentive stimuli can evoke cravings in those with drug addiction, a better understanding of the mechanisms of incentive learning may lead to the development of solutions for these individuals.

Stigmatisation of EU mobile citizens: a ticking time bomb for the European project. EPC Commentary, 24 January 2014

The 2013 European Year of Citizens was profoundly marked by escalating attacks against one of the EU’s major achievement for EU citizens: freedom of movement. In April 2013, Home Affairs Ministers from Austria, Germany, the Netherlands and the UK were party to a letter claiming that “a significant number of new immigrants draw social assistance in the host countries, frequently without genuine entitlement, burdening host societies’ social welfare systems”. This letter laid the groundwork for a “battle plan”, presented by David Cameron in November, which aimed to make the free movement of persons “less free” and put forward the idea of capping “EU migration”. Furthermore, in December, the German conservative Christian Social Union (CSU) took up a similar petty political discourse. After the end of the transitional period for Romania and Bulgaria on 1 January 2014, the debate continues with Chuka Umunna (British Labour Party) proposing to restrict the freedom of movement to highly skilled EU citizens and to citizens in possession of a firm job offer. Alongside this, the German Chancellor, Angela Merkel announced the formation of a committee to investigate “poverty migration” in Germany. This wave of resentment has been more recently followed by the UK Prime Minister David Cameron, expressing his intention to re-negotiate EU law in order to be able to withdraw child benefits from EU citizens working in the UK, citing Polish citizens working in the UK as an example. Seeing this as a stigmatisation of the Polish population, the Polish foreign minister, Radosław Sikorski, qualified Cameron’s discourse as “unacceptable”. The debate over limiting freedom of movement has continuously escalated and reached a worrying level. With the EP elections approaching in May 2014, this debate is likely to become worse.

Migration and War Memory in a European Perspective A Case-Study on Displaced Persons in Belgium. Natolin Research Paper 05/2011

In the aftermath of World War II, about 20,000 people who had experienced displacement entered Belgium.1 Among those there were about 350 soldiers serving in the Polish armed forces in the West, and about 4,000 ostarbeiterinnen - young female Soviet citizens who were deported to Nazi Germany to do forced labour. All the soldiers and Soviet women married Belgian citizens, and most settled in the home town or city of their spouses. This paper focuses on the war memories of these migrants in post-war life, memories that were arguably shaped not only by the characteristics of their war experiences themselves, but also by the changing positions which they held within their home and host societies. Following the migrants from their moment of settlement until today, the article highlights the changing dynamics of their war memories over time, starting during the Cold War era and ending up in present day Europe. As such, the study finds itself on the crossroads of memory and migration studies, two academic disciplines that only recently started to dialogue with each other.2 Before analysing the arrival, settlement and war memories of the Displaced Persons at study, I give an interpretation of academic literature on memory of World War II from the perspective of migration studies.

Event marketing: an innovative promotional tool and its impact on consumer memory and brand awareness

Event Marketing represents a common promotional strategy that involves direct contact between brands and consumers at special events, namely concerts, festivals, sporting events and fairs. Brands have been investing in sponsorship as a means of associating themselves with particular events, essentially with the goal to enhance brand image and brand awareness. Interestingly, the response of consumers to event marketing has not yet been fully understood. This dissertation fills this gap. More specifically, it intends to determine the extent to which sponsoring brands at events favors brand awareness (recall and recognition) and how it relates to brand attitude. Based on three Portuguese music festivals, two studies were conducted to ascertain event sponsorship’s impact on consumer memory, notably Brand Recall and Brand Recognition, and correlation with attitudes towards the brands such as familiarity and liking. The key findings of these studies show that recognition is much higher for those respondents who attended the festivals, presenting a score of 73,9%, in comparison with recall, presenting a much lower score of 37,5%. Further, and surprisingly, it suggests that the ability to recall and recognize sponsoring brands is not associated to consumer attitudes towards the brands. Instead, it relates to the time consumers dedicated to these particular events, that is, the number of music festivals attended.

The relationship between diurnal type and time duration estimation at morning and evening times of day

This study investigates whether different diurnal types (morning versus evening) differ in their estimation of time duration at different times of the day. Given that the performance of morning and evening types is typically best at their preferred times of day, and assuming different diurnal trends in subjective alertness (arousal?) for morning and evening types, and adopting the attentional gate model of time duration estimation, it was predicted that morning types would tend to underestimate and be more accurate in the morning compared to evening types where the opposite pattern was expected. Nineteen morning types, 18 evening types and 18 intermediate types were drawn from a large sample (N=1175) of undergraduates administered the Early/Late Preference Scale. Groups performed a time duration estimation task using the production method for estimating 20-s unfilled intervals at two times of day: 0800/1830. The median absolute error, median directional error and frequency of under- and overestimation were analysed using repeated-measures ANOVA. While all differences were statistically non-significant, the following trends were observed: morning types performed better than evening types; participants overestimated in the morning and underestimated in the evening; and participants were more accurate later in the day. It was concluded that the trends are inconsistent with a relationship between subjective alertness and time duration estimation but consistent with a possible relationship between time duration estimation and diurnal body temperature fluctuations. (C) 2002 Elsevier Ltd. All rights reserved.