Traits of fear resistance and susceptibility in an advanced intercross line

Genetic variability in the strength and precision of fear memory is hypothesised to contribute to the etiology of anxiety disorders, including post-traumatic stress disorder. We generated fear-susceptible (F-S) or fear-resistant (F-R) phenotypes from an F8 advanced intercross line (AIL) of C57BL/6J and DBA/2J inbred mice by selective breeding. We identified specific traits underlying individual variability in Pavlovian conditioned fear learning and memory. Offspring of selected lines differed in the acquisition of conditioned fear. Furthermore, F-S mice showed greater cued fear memory and generalised fear in response to a novel context than F-R mice. F-S mice showed greater basal corticosterone levels and hypothalamic corticotrophin-releasing hormone (CRH) mRNA levels than F-R mice, consistent with higher hypothalamic-pituitary-adrenal (HPA) axis drive. Hypothalamic mineralocorticoid receptor and CRH receptor 1 mRNA levels were decreased in F-S mice as compared with F-R mice. Manganese-enhanced magnetic resonance imaging (MEMRI) was used to investigate basal levels of brain activity. MEMRI identified a pattern of increased brain activity in F-S mice that was driven primarily by the hippocampus and amygdala, indicating excessive limbic circuit activity in F-S mice as compared with F-R mice. Thus, selection pressure applied to the AIL population leads to the accumulation of heritable trait-relevant characteristics within each line, whereas non-behaviorally relevant traits remain distributed. Selected lines therefore minimise false-positive associations between behavioral phenotypes and physiology. We demonstrate that intrinsic differences in HPA axis function and limbic excitability contribute to phenotypic differences in the acquisition and consolidation of associative fear memory. Identification of system-wide traits predisposing to variability in fear memory may help in the direction of more targeted and efficacious treatments for fear-related pathology. Through short-term selection in a B6D2 advanced intercross line we created mouse populations divergent for the retention of Pavlovian fear memory. Trait distinctions in HPA-axis drive and fear network circuitry could be made between naïve animals in the two lines. These data demonstrate underlying physiological and neurological differences between Fear-Susceptible and Fear-Resistant animals in a natural population. F-S and F-R mice may therefore be relevant to a spectrum of disorders including depression, anxiety disorders and PTSD for which altered fear processing occurs.

Neurons Activated During Fear Memory Consolidation and Reconsolidation are Mapped to a Common and New Topography in the Lateral Amygdala

A key question in neuroscience is how memory is selectively allocated to neural networks in the brain. This question remains a significant research challenge, in both rodent models and humans alike, because of the inherent difficulty in tracking and deciphering large, highly dimensional neuronal ensembles that support memory (i.e., the engram). In a previous study we showed that consolidation of a new fear memory is allocated to a common topography of amygdala neurons. When a consolidated memory is retrieved, it may enter a labile state, requiring reconsolidation for it to persist. What is not known is whether the original spatial allocation of a consolidated memory changes during reconsolidation. Knowledge about the spatial allocation of a memory, during consolidation and reconsolidation, provides fundamental insight into its core physical structure (i.e., the engram). Using design-based stereology, we operationally define reconsolidation by showing a nearly identical quantity of neurons in the dorsolateral amygdala (LAd) that expressed a plasticity-related protein, phosphorylated mitogen-activated protein kinase, following both memory acquisition and retrieval. Next, we confirm that Pavlovian fear conditioning recruits a stable, topographically organized population of activated neurons in the LAd. When the stored fear memory was briefly reactivated in the presence of the relevant conditioned stimulus, a similar topography of activated neurons was uncovered. In addition, we found evidence for activated neurons allocated to new regions of the LAd. These findings provide the first insight into the spatial allocation of a fear engram in the LAd, during its consolidation and reconsolidation phase.

Pavlovian fear memory circuits and phenotype models of PTSD

Pavlovian fear conditioning, also known as classical fear conditioning is an important model in the study of the neurobiology of normal and pathological fear. Progress in the neurobiology of Pavlovian fear also enhances our understanding of disorders such as posttraumatic stress disorder (PTSD) and with developing effective treatment strategies. Here we describe how Pavlovian fear conditioning is a key tool for understanding both the neurobiology of fear and the mechanisms underlying variations in fear memory strength observed across different phenotypes. First we discuss how Pavlovian fear models aspects of PTSD. Second, we describe the neural circuits of Pavlovian fear and the molecular mechanisms within these circuits that regulate fear memory. Finally, we show how fear memory strength is heritable; and describe genes which are specifically linked to both changes in Pavlovian fear behavior and to its underlying neural circuitry. These emerging data begin to define the essential genes, cells and circuits that contribute to normal and pathological fear.

Pavlovian Fear Conditioning Activates a Common Pattern of Neurons in the Lateral Amygdala of Individual Brains

Understanding the physical encoding of a memory (the engram) is a fundamental question in neuroscience. Although it has been established that the lateral amygdala is a key site for encoding associative fear memory, it is currently unclear whether the spatial distribution of neurons encoding a given memory is random or stable. Here we used spatial principal components analysis to quantify the topography of activated neurons, in a select region of the lateral amygdala, from rat brains encoding a Pavlovian conditioned fear memory. Our results demonstrate a stable, spatially patterned organization of amygdala neurons are activated during the formation of a Pavlovian conditioned fear memory. We suggest that this stable neuronal assembly constitutes a spatial dimension of the engram. © 2011 This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Identifying the unknown in user space memory

This thesis is a study of how the contents of volatile memory on the Windows operating system can be better understood and utilised for the purposes of digital forensic investigations. It proposes several techniques to improve the analysis of memory, with a focus on improving the detection of unknown code such as malware. These contributions allow the creation of a more complete reconstruction of the state of a computer at acquisition time, including whether or not the computer has been infected by malicious code.

A recurrent network in the lateral amygdala : a mechanism for coincidence detection

Synaptic changes at sensory inputs to the dorsal nucleus of the lateral amygdala (LAd) play a key role in the acquisition and storage of associative fear memory. However, neither the temporal nor spatial architecture of the LAd network response to sensory signals is understood. We developed a method for the elucidation of network behavior. Using this approach, temporally patterned polysynaptic recurrent network responses were found in LAd (intra-LA), both in vitro and in vivo, in response to activation of thalamic sensory afferents. Potentiation of thalamic afferents resulted in a depression of intra-LA synaptic activity, indicating a homeostatic response to changes in synaptic strength within the LAd network. Additionally, the latencies of thalamic afferent triggered recurrent network activity within the LAd overlap with known later occurring cortical afferent latencies. Thus, this recurrent network may facilitate temporal coincidence of sensory afferents within LAd during associative learning.

Myosin light chain kinase regulates synaptic plasticity and fear learning in the lateral amygdala

Learning and memory depend on signaling mole- cules that affect synaptic efficacy. The cytoskeleton has been implicated in regulating synaptic transmission but its role in learning and memory is poorly understood. Fear learning depends on plasticity in the lateral nucleus of the amygdala. We therefore examined whether the cytoskeletal-regulatory protein, myosin light chain kinase, might contribute to fear learning in the rat lateral amygdala. Microinjection of ML-7, a specific inhibitor of myosin light chain kinase, into the lateral nucleus of the amygdala before fear conditioning, but not immediately afterward, enhanced both short-term memory and long-term memory, suggesting that myosin light chain kinase is involved specifically in memory acquisition rather than in posttraining consolidation of memory. Myosin light chain kinase inhibitor had no effect on memory retrieval. Furthermore, ML-7 had no effect on behavior when the train- ing stimuli were presented in a non-associative manner. An- atomical studies showed that myosin light chain kinase is present in cells throughout lateral nucleus of the amygdala and is localized to dendritic shafts and spines that are postsynaptic to the projections from the auditory thalamus to lateral nucleus of the amygdala, a pathway specifically impli- cated in fear learning. Inhibition of myosin light chain kinase enhanced long-term potentiation, a physiological model of learning, in the auditory thalamic pathway to the lateral nu- cleus of the amygdala. When ML-7 was applied without as- sociative tetanic stimulation it had no effect on synaptic responses in lateral nucleus of the amygdala. Thus, myosin light chain kinase activity in lateral nucleus of the amygdala appears to normally suppress synaptic plasticity in the cir- cuits underlying fear learning, suggesting that myosin light chain kinase may help prevent the acquisition of irrelevant fears. Impairment of this mechanism could contribute to pathological fear learning.

CAM : a collaborative object memory system

Physical design objects such as sketches, drawings, collages, storyboards and models play an important role in supporting communication and coordination in design studios. CAM (Cooperative Artefact Memory) is a mobile-tagging based messaging system that allows designers to collaboratively store relevant information onto their design objects in the form of messages, annotations and external web links. We studied the use of CAM in a Product Design studio over three weeks, involving three different design teams. In this paper, we briefly describe CAM and show how it serves as 'object memory'.

BDNF and TNF-α polymorphisms in memory

Here, we investigate the genetic basis of human memory in healthy individuals and the potential role of two polymorphisms, previously implicated in memory function. We have explored aspects of retrospective and prospective memory including semantic, short term, working and long-term memory in conjunction with brain derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-alpha). The memory scores for healthy individuals in the population were obtained for each memory type and the population was genotyped via restriction fragment length polymorphism for the BDNF rs6265 (Val66Met) SNP and via pyrosequencing for the TNF-alpha rs113325588 SNP. Using univariate ANOVA, a significant association of the BDNF polymorphism with visual and spatial memory retention and a significant association of the TNF-alpha polymorphism was observed with spatial memory retention. In addition, a significant interactive effect between BDNF and TNF-alpha polymorphisms was observed in spatial memory retention. In practice visual memory involves spatial information and the two memory systems work together, however our data demonstrate that individuals with the Val/Val BDNF genotype have poorer visual memory but higher spatial memory retention, indicating a level of interaction between TNF-alpha and BDNF in spatial memory retention. This is the first study to use genetic analysis to determine the interaction between BDNF and TNF-alpha in relation to memory in normal adults and provides important information regarding the effect of genetic determinants and gene interactions on human memory.

Joint identification of infinite-frequency added mass and fluid-memory models of marine structures

This paper addresses the problem of joint identification of infinite-frequency added mass and fluid memory models of marine structures from finite frequency data. This problem is relevant for cases where the code used to compute the hydrodynamic coefficients of the marine structure does not give the infinite-frequency added mass. This case is typical of codes based on 2D-potential theory since most 3D-potential-theory codes solve the boundary value associated with the infinite frequency. The method proposed in this paper presents a simpler alternative approach to other methods previously presented in the literature. The advantage of the proposed method is that the same identification procedure can be used to identify the fluid-memory models with or without having access to the infinite-frequency added mass coefficient. Therefore, it provides an extension that puts the two identification problems into the same framework. The method also exploits the constraints related to relative degree and low-frequency asymptotic values of the hydrodynamic coefficients derived from the physics of the problem, which are used as prior information to refine the obtained models.

Cork as canvas : exploring intersections of citizenship and collective memory in the Shandon Big Wash Up murals

Urban space has the potential to shape people's experience and understanding of the city and of the culture of a place. In some respects, murals and allied forms of wall art occupy the intersection of street art and public art; engaging, and sometimes, transforming the urban space in which they exist and those who use it. While murals are often conceived as a more ‘permanent’ form of painted art there has been a trend in recent years towards more deliberately transient forms of wall art such as washed-wall murals and reverse graffiti. These varying forms of public wall art are embedded within the fabric of the urban space and history. This paper will explore the intersection of public space, public art and public memory in a mural project in the Irish city of Cork. Focussing on the washed-wall murals of Cork's historic Shandon district, we explore the sympathetic and synergetic relationship of this wall art with the heritage architecture of the built environment and of the murals as an expression of and for the local community, past and present. Through the Shandon Big Wash Up murals we reflect on the function of participatory public art as an explicit act of urban citizenship which works to support community-led re-enchantment in the city through a reconnection with its past.

Developing transactive memory systems : theoretical contributions from a social identity perspective

Transactive memory system (TMS) theory explains how expertise is recognized and coordinated in teams. Extending current TMS research from a group information-processing perspective, our article presents a theoretical model that considers TMS development from a social identity perspective. We discuss how two features of communication (quantity and quality) important to TMS development are linked to TMS through the group identification mechanism of a shared common team identity. Informed by social identity theory, we also differentiate between intragroup and intergroup contexts and outline how, in multidisciplinary teams, professional identification and perceived equality of status among professional subgroups have a role to play in TMS development. We provide a theoretical discussion of future research directions aimed at testing and extending our model.

Orientation dependence of spatial memory acquired from auditory experience

The present study investigated whether memory for a room-sized spatial layout learned through auditory localization of sounds exhibits orientation dependence similar to that observed for spatial memory acquired from stationary viewing of the environment. Participants learned spatial layouts by viewing objects or localizing sounds and then performed judgments of relative direction among remembered locations. The results showed that direction judgments following auditory learning were performed most accurately at a particular orientation in the same way as were those following visual learning, indicating that auditorily encoded spatial memory is orientation dependent. In combination with previous findings that spatial memories derived from haptic and proprioceptive experiences are also orientation dependent, the present finding suggests that orientation dependence is a general functional property of human spatial memory independent of learning modality.

Visual and proprioceptive representations in spatial memory

It has been shown that spatial information can be acquired from both visual and nonvisual modalities. The present study explored how spatial information from vision and proprioception was represented in memory, investigating orientation dependence of spatial memories acquired through visual and proprioceptive spatial learning. Experiment 1 examined whether visual learning alone and proprioceptive learning alone yielded orientation-dependent spatial memory. Results showed that spatial memories from both types of learning were orientation dependent. Experiment 2 explored how different orientations of the same environment were represented when they were learned visually and proprioceptively. Results showed that both visually and proprioceptively learned orientations were represented in spatial memory, suggesting that participants established two different reference systems based on each type of learning experience and interpreted the environment in terms of these two reference systems. The results provide some initial clues to how different modalities make unique contributions to spatial representations.