PLCß介导的钙调腺苷酸环化酶在突触可塑性相关基因转录中的作用和FE65对海马依赖学习及LTP的调节

Gene regulation is required for activity-dependent changes in synaptic plasticity and remodeling. The metabotropic glutamate receptors (mGluRs) contribute to different brain functions, including learning/memory, mental disorders, drug addiction, and persistent pain in the CNS. We found that Gp I mGluRs activate PLCß through Gq and then lead to activation of several calcium-dependent signaling pathways, including ERK, which play an important role in gene transcription. These findings support a calcium-dependent role for Gq in release of Calcium and activation of calcium-stimulated adenylyl cyclases I in activity-dependent transcription in response to application of group I metabotropic glutamate receptors agonist and may provide insights into group I mGluRs-dependent synaptic plasticity through MAP kinases signaling. Moreover, the present study investigated the transcription-dependent changes of Arc in response to the activation of group I mGluRs and suggested the central role of ERK1/2 in group I mGluR-mediated Arc transcription. Further, we selected APP-interaction protein FE65 to investigate the mechanism of transcription-related process in synaptic plasticity. FE65 is expressed predominantly in the brain, and interacts with the C-terminal domain of β-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with the isoform-specific FE65 knock-out (p97FE65-/-) mice. p97FE65 knock-out mice showed impaired short-term memory for both TDPA and CFC when tested 10min after training, which is transcription-independent. Consistently, at the Schaffer collateral-CA1 synapses, p97FE65 knock-out mice showed defective early phase LTP. These results demonstrate novel roles of FE65 in synaptic plasticity, acquisition, and retention for certain forms of memory formation.

长时记忆中图形不同特征的加工与提取

Information can be represented both conceptually and imaginarily in long-term memory. However, it seems that only conceptual representation appears, neglecting imaginary information, in most of the long-term memory (LTM) models. In the matter of fact, picture can be stored in LTM directly and conceptually. There is no evidence for what specific type of information, conceptual or imaginary, for the color, shape, or texture to be represented. However, it is evident that the shape and color can be represented separately in LMT. Further research is needed on whether features are represented separately or not, such as color and texture, texture and shape etc. Rehearsal plays important role in picture memory besides the types of storage and representation. Memory of picture is indeed enhanced by rehearsal. There are two types of rehearsal. One is for creating image, another is articulatory loop. Which one will be taken during picture memory process depends on the characteristics of stimuli, subjects' encoding preferences and/or task requirements. Nevertheless, the relation between two types of rehearsal is not very clear yet up to now. Different features could be activated at different time course or possibilities since they can be represented separately. Six experiments were conducted dealing with the characteristics of representation, rehearsal and retrieval of picture in LTM. From these experiments, further understanding of picture information processing was expected. It would add more evidence to the LTM models, and make practical sense to the computer visual identification. The first two experiments were based on the paradigm from Hanna et al.(1996) to investigate separable representation of texture and shape, texture and color. The results indicated that texture could be represented separately with color and shape respectively. It suggested that different features might be processed in different way during remembering. Another interest finding is that recognition performance for shape, color and texture are quite different. What for shape is highest, for color is lowest, and for texture is between of them. Three features of picture can be represented separately. How about the roles of rehearsal when they enter the LTM from short-term memory(STM)? The second three experiments assigned three different types of rehearsal, i. e. visual, verbal, and subject-run(might be both of visual and verbal). The findings are that performances of picture memory were affected significantly by different types of rehearsal. Both visual and verbal rehearsal played important role during remembering process. It seems that verbal rehearsal, which might enhance the relative strength of memory trace, was much more effective than visual one. In addition, subjects tended to choose those difficult-to-name, features to rehearse, to improve the memory performance. Only two features were changed in each of the first two experiments. They might interact (facilitate or disturb) each other when they were retrieved. So it was difficult to identify the retrieval difference between them. In the last experiment, easy-to-name pictures were studied, and only one feature could be recognized. The results indicated that the retrieval performances of three features(shape, color, and texture) were quite different. They were different on the relative strength of memory trace, with the shape was strongest, color was lightest, and texture was in between. No difference was found on the absolute strength of them.

记忆年老化与焦虑

It is well established that memory functioning deteriorates with advancing age. However, research indicates that the magnitude of age-related memory deficits varies across different types of memory, and broad individual differences can be observed in the rate and timing of memory aging. The general aim of this study was to investigate the selectivity and variability of memory functioning in relation to anxiety. Firstly, memory effectiveness was assessed in episodic memory tasks with reality monitoring and external source monitoring paradigms, semantic memory tasks referred to general knowledge and word fluency, and perceptual priming task reflected in word completion. According to the scores on trait version of STAI, the high-trait and low-trait anxious subjects were screened respectively from young and old participants matched for educational level. Secondly, based on the results of the first part, concurrent primary and secondary tasks with probe technique assessing spare processing capacity were used to explore the relation between memory efficiency and anxiety. The first main findings were that: (a) there were no age-related differences in semantic memory assessed by general knowledge and PRS, whereas age effects were observed in episodic memory and semantic memory assessed by word fluency with stringent time restraints. (b) Furthermore, comparison of age-related deficits in source and item was not related to the presentation ways and encoding effort for source, but was affected by types of source. Specifically, memory was more sensitive to aging than item memory in external source monitoring processes involved in discriminating two external sources (i.e., female vs. male voices), but not in reality monitoring processes in discriminating between internal and external sources (i.e., acting vs. listening). The second main findings were that: (a) Anxiety had no effects on the effectiveness and efficiency of semantic memory in recall of general knowledge and PRS, but impaired those of semantic memory in word fluency. (b) The effects of anxiety on episodic memory were different between the old and the young. Both the effectiveness and the efficiency of episodic memory of the old were affected adversely by anxiety. More importantly, source recall in external source monitoring processes was observed to be more vulnerable to anxiety than item memory. The effectiveness of episodic memory of the young was relatively unrelated to anxiety, while anxiety might have adverse effect on their memory efficiency. These results indicated that: First, the selectivity of age-related memory deficits existed not only between memory systems, but also within episodic memory system. The tendency to forget the source even when the fact was retained in external source monitoring was suggested to be a specific feature of cognitive aging. Second, anxiety had adverse impact on the individual differences in memory aging, and mediated partial age-related differences in episodic memory performance.

樟柳碱和石杉碱甲对学习和记忆的影响及其有关机制的研究

Two experiments were designed to examine the role of the cholinergic agents, anisodine and huperzine A, and related mechanisms. In experiment 1, the effects of anisodine and huperzine A on rat performance in Morris water maze were observed. It was found that the drugs injected before daily training had significant effect on performance of place navigation task and transfer test, while the drugs injected after daily training, before retest and overtraining had no such effect. the results indicated that the drugs, which only have effects on reference memory related to cognitive mapping strategy, may mediate the acquisition process of memory. In experiment 2, the spontaneous hippocampol neuronal activities and the effects of the drugs on them in awake rabbits were observed. The results showed that anisodine had significant inhibitory effect on the activities, the opposite effect was found in huperzine A. Furthermore, sensory stimulation and administration of huperzine A have similar effects. It was sujested that hipppocampus be directly relavent to transmission of information to memory storage system, in which the role of central cholinergic system is critical.

Garbage Collection is Fast, But a Stack is Faster

Prompted by claims that garbage collection can outperform stack allocation when sufficient physical memory is available, we present a careful analysis and set of cross-architecture measurements comparing these two approaches for the implementation of continuation (procedure call) frames. When the frames are allocated on a heap they require additional space, increase the amount of data transferred between memory and registers, and, on current architectures, require more instructions. We find that stack allocation of continuation frames outperforms heap allocation in some cases by almost a factor of three. Thus, stacks remain an important implementation technique for procedure calls, even in the presence of an efficient, compacting garbage collector and large amounts of memory.

A Coupled Multi-ALU Processing Node for a Highly Parallel Computer

This report describes Processor Coupling, a mechanism for controlling multiple ALUs on a single integrated circuit to exploit both instruction-level and inter-thread parallelism. A compiler statically schedules individual threads to discover available intra-thread instruction-level parallelism. The runtime scheduling mechanism interleaves threads, exploiting inter-thread parallelism to maintain high ALU utilization. ALUs are assigned to threads on a cycle byscycle basis, and several threads can be active concurrently. Simulation results show that Processor Coupling performs well both on single threaded and multi-threaded applications. The experiments address the effects of memory latencies, function unit latencies, and communication bandwidth between function units.

Sparsely Faceted Arrays: A Mechanism Supporting Parallel Allocation, Communication, and Garbage Collection

Conventional parallel computer architectures do not provide support for non-uniformly distributed objects. In this thesis, I introduce sparsely faceted arrays (SFAs), a new low-level mechanism for naming regions of memory, or facets, on different processors in a distributed, shared memory parallel processing system. Sparsely faceted arrays address the disconnect between the global distributed arrays provided by conventional architectures (e.g. the Cray T3 series), and the requirements of high-level parallel programming methods that wish to use objects that are distributed over only a subset of processing elements. A sparsely faceted array names a virtual globally-distributed array, but actual facets are lazily allocated. By providing simple semantics and making efficient use of memory, SFAs enable efficient implementation of a variety of non-uniformly distributed data structures and related algorithms. I present example applications which use SFAs, and describe and evaluate simple hardware mechanisms for implementing SFAs. Keeping track of which nodes have allocated facets for a particular SFA is an important task that suggests the need for automatic memory management, including garbage collection. To address this need, I first argue that conventional tracing techniques such as mark/sweep and copying GC are inherently unscalable in parallel systems. I then present a parallel memory-management strategy, based on reference-counting, that is capable of garbage collecting sparsely faceted arrays. I also discuss opportunities for hardware support of this garbage collection strategy. I have implemented a high-level hardware/OS simulator featuring hardware support for sparsely faceted arrays and automatic garbage collection. I describe the simulator and outline a few of the numerous details associated with a "real" implementation of SFAs and SFA-aware garbage collection. Simulation results are used throughout this thesis in the evaluation of hardware support mechanisms.

Brought to Light

Poster, Jeremy, Brought to Light (Northumberland: Bloodaxe, 2001) RAE2008

What children learn from adults’ utterances: an ephemeral lexical boost and persistent syntactic priming in adult–child dialogue

We show that children’s syntactic production is immediately affected by individual experiences of structures and verb–structure pairings within a dialogue, but that these effects have different timecourses. In a picture-matching game, three- to four-year-olds were more likely to describe a transitive action using a passive immediately after hearing the experimenter produce a passive than an active (abstract priming), and this tendency was stronger when the verb was repeated (lexical boost). The lexical boost disappeared after two intervening utterances, but the abstract priming effect persisted. This pattern did not differ significantly from control adults. Children also showed a cumulative priming effect. Our results suggest that whereas the same mechanism may underlie children’s immediate syntactic priming and long-term syntactic learning, different mechanisms underlie the lexical boost versus long-term learning of verb–structure links. They also suggest broad continuity of syntactic processing in production between this age group and adults.

Indexing Distances in Large Graphs and Applications in Search Tasks

This thesis elaborates on the problem of preprocessing a large graph so that single-pair shortest-path queries can be answered quickly at runtime. Computing shortest paths is a well studied problem, but exact algorithms do not scale well to real-world huge graphs in applications that require very short response time. The focus is on approximate methods for distance estimation, in particular in landmarks-based distance indexing. This approach involves choosing some nodes as landmarks and computing (offline), for each node in the graph its embedding, i.e., the vector of its distances from all the landmarks. At runtime, when the distance between a pair of nodes is queried, it can be quickly estimated by combining the embeddings of the two nodes. Choosing optimal landmarks is shown to be hard and thus heuristic solutions are employed. Given a budget of memory for the index, which translates directly into a budget of landmarks, different landmark selection strategies can yield dramatically different results in terms of accuracy. A number of simple methods that scale well to large graphs are therefore developed and experimentally compared. The simplest methods choose central nodes of the graph, while the more elaborate ones select central nodes that are also far away from one another. The efficiency of the techniques presented in this thesis is tested experimentally using five different real world graphs with millions of edges; for a given accuracy, they require as much as 250 times less space than the current approach which considers selecting landmarks at random. Finally, they are applied in two important problems arising naturally in large-scale graphs, namely social search and community detection.

Fast Shortest Path Distance Estimation in Large Networks

We study the problem of preprocessing a large graph so that point-to-point shortest-path queries can be answered very fast. Computing shortest paths is a well studied problem, but exact algorithms do not scale to huge graphs encountered on the web, social networks, and other applications. In this paper we focus on approximate methods for distance estimation, in particular using landmark-based distance indexing. This approach involves selecting a subset of nodes as landmarks and computing (offline) the distances from each node in the graph to those landmarks. At runtime, when the distance between a pair of nodes is needed, we can estimate it quickly by combining the precomputed distances of the two nodes to the landmarks. We prove that selecting the optimal set of landmarks is an NP-hard problem, and thus heuristic solutions need to be employed. Given a budget of memory for the index, which translates directly into a budget of landmarks, different landmark selection strategies can yield dramatically different results in terms of accuracy. A number of simple methods that scale well to large graphs are therefore developed and experimentally compared. The simplest methods choose central nodes of the graph, while the more elaborate ones select central nodes that are also far away from one another. The efficiency of the suggested techniques is tested experimentally using five different real world graphs with millions of edges; for a given accuracy, they require as much as 250 times less space than the current approach in the literature which considers selecting landmarks at random. Finally, we study applications of our method in two problems arising naturally in large-scale networks, namely, social search and community detection.

Towards Formalizing Java's Weak References

Weak references provide the programmer with limited control over the process of memory management. By using them, a programmer can make decisions based on previous actions that are taken by the garbage collector. Although this is often helpful, the outcome of a program using weak references is less predictable due to the nondeterminism they introduce in program evaluation. It is therefore desirable to have a framework of formal tools to reason about weak references and programs that use them. We present several calculi that formalize various aspects of weak references, inspired by their implementation in Java. We provide a calculus to model multiple levels of non-strong references, where a different garbage collection policy is applied to each level. We consider different collection policies such as eager collection and lazy collection. Similar to the way they are implemented in Java, we give the semantics of eager collection to weak references and the semantics of lazy collection to soft references. Moreover, we condition garbage collection on the availability of time and space resources. While time constraints are used in order to restrict garbage collection, space constraints are used in order to trigger it. Finalizers are a problematic feature in Java, especially when they interact with weak references. We provide a calculus to model finalizer evaluation. Since finalizers have little meaning in a language without side-effect, we introduce a limited form of side effect into the calculus. We discuss determinism and the separate notion of uniqueness of (evaluation) outcome. We show that in our calculus, finalizer evaluation does not affect uniqueness of outcome.

Nanostructured ferroelectric materials

Nanostructured materials are central to the evolution of future electronics and information technologies. Ferroelectrics have already been established as a dominant branch in the electronics sector because of their diverse application range such as ferroelectric memories, ferroelectric tunnel junctions, etc. The on-going dimensional downscaling of materials to allow packing of increased numbers of components onto integrated circuits provides the momentum for the evolution of nanostructured ferroelectric materials and devices. Nanoscaling of ferroelectric materials can result in a modification of their functionality, such as phase transition temperature or Curie temperature (TC), domain dynamics, dielectric constant, coercive field, spontaneous polarisation and piezoelectric response. Furthermore, nanoscaling can be used to form high density arrays of monodomain ferroelectric nanostructures, which is desirable for the miniaturisation of memory devices. This thesis details the use of various types of nanostructuring approaches to fabricate arrays of ferroelectric nanostructures, particularly non-oxide based systems. The introductory chapter reviews some exemplary research breakthroughs in the synthesis, characterisation and applications of nanoscale ferroelectric materials over the last decade, with priority given to novel synthetic strategies. Chapter 2 provides an overview of the experimental methods and characterisation tools used to produce and probe the properties of nanostructured antimony sulphide (Sb2S3), antimony sulpho iodide (SbSI) and lead titanate zirconate (PZT). In particular, Chapter 2 details the general principles of piezoresponse microscopy (PFM). Chapter 3 highlights the fabrication of arrays of Sb2S3 nanowires with variable diameters using newly developed solventless template-based approach. A detailed account of domain imaging and polarisation switching of these nanowire arrays is also provided. Chapter 4 details the preparation of vertically aligned arrays of SbSI nanorods and nanowires using a surface-roughness assisted vapour-phase deposition method. The qualitative and quantitative nanoscale ferroelectric properties of these nanostructures are also discussed. Chapter 5 highlights the fabrication of highly ordered arrays of PZT nanodots using block copolymer self-assembled templates and their ferroelectric characterisation using PFM. Chapter 6 summarises the conclusions drawn from the results reported in chapters 3, 4 and 5 and the future work.

Entorhinal cortex volume in older adults: reliability and validity considerations for three published measurement protocols.

Measuring the entorhinal cortex (ERC) is challenging due to lateral border discrimination from the perirhinal cortex. From a sample of 39 nondemented older adults who completed volumetric image scans and verbal memory indices, we examined reliability and validity concerns for three ERC protocols with different lateral boundary guidelines (i.e., Goncharova, Dickerson, Stoub, & deToledo-Morrell, 2001; Honeycutt et al., 1998; Insausti et al., 1998). We used three novice raters to assess inter-rater reliability on a subset of scans (216 total ERCs), with the entire dataset measured by one rater with strong intra-rater reliability on each technique (234 total ERCs). We found moderate to strong inter-rater reliability for two techniques with consistent ERC lateral boundary endpoints (Goncharova, Honeycutt), with negligible to moderate reliability for the technique requiring consideration of collateral sulcal depth (Insausti). Left ERC and story memory associations were moderate and positive for two techniques designed to exclude the perirhinal cortex (Insausti, Goncharova), with the Insausti technique continuing to explain 10% of memory score variance after additionally controlling for depression symptom severity. Right ERC-story memory associations were nonexistent after excluding an outlier. Researchers are encouraged to consider challenges of rater training for ERC techniques and how lateral boundary endpoints may impact structure-function associations.

Spike avalanches exhibit universal dynamics across the sleep-wake cycle.

BACKGROUND: Scale-invariant neuronal avalanches have been observed in cell cultures and slices as well as anesthetized and awake brains, suggesting that the brain operates near criticality, i.e. within a narrow margin between avalanche propagation and extinction. In theory, criticality provides many desirable features for the behaving brain, optimizing computational capabilities, information transmission, sensitivity to sensory stimuli and size of memory repertoires. However, a thorough characterization of neuronal avalanches in freely-behaving (FB) animals is still missing, thus raising doubts about their relevance for brain function. METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we employed chronically implanted multielectrode arrays (MEA) to record avalanches of action potentials (spikes) from the cerebral cortex and hippocampus of 14 rats, as they spontaneously traversed the wake-sleep cycle, explored novel objects or were subjected to anesthesia (AN). We then modeled spike avalanches to evaluate the impact of sparse MEA sampling on their statistics. We found that the size distribution of spike avalanches are well fit by lognormal distributions in FB animals, and by truncated power laws in the AN group. FB data surrogation markedly decreases the tail of the distribution, i.e. spike shuffling destroys the largest avalanches. The FB data are also characterized by multiple key features compatible with criticality in the temporal domain, such as 1/f spectra and long-term correlations as measured by detrended fluctuation analysis. These signatures are very stable across waking, slow-wave sleep and rapid-eye-movement sleep, but collapse during anesthesia. Likewise, waiting time distributions obey a single scaling function during all natural behavioral states, but not during anesthesia. Results are equivalent for neuronal ensembles recorded from visual and tactile areas of the cerebral cortex, as well as the hippocampus. CONCLUSIONS/SIGNIFICANCE: Altogether, the data provide a comprehensive link between behavior and brain criticality, revealing a unique scale-invariant regime of spike avalanches across all major behaviors.