bluuebunny/crossref_metadata_2025 huggingface dataset:
Some Demonstrations of the Effects of Structural Descriptions in Mental Imagery*
Authors: Hinton Geoffrey
Published: October 2005

A visual imagery task is presented which is beyond the limits of normal human ability, and some of the factors contributing to its difficulty are isolated by comparing the difficulty of related tasks. It is argued that complex objects are assigned hierarchical structural descriptions by being parsed into parts, each of which has its own local system of significant directions. Two quite different schemas for a wire‐frame cube are used to illustrate this theory, and some striking perceptual differences to which they give rise are described. The difficulty of certain mental imagery tasks is shown to depend on which of the alternative structural descriptions of an object is used, and this is interpreted as evidence that structural descriptions are an important component of mental images. Finally, it is argued that analog transformations like mental folding involve changing the values of continuous variables in a structural description.
Prediction and Substantiation: A New Approach to Natural Language Processing*
Authors: DeJong Gerald
Published: October 2005

This paper describes a new approach to natural language processing which results in a very robust and efficient system. The approach taken is to integrate the parser with the rest of the system. This enables the parser to benefit from predictions that the rest of the system makes in the course of its processing. These predictions can be invaluable as guides to the parser in such difficult problem areas as resolving referents and selecting meanings of ambiguous words. A program, called FRUMP for Fast Reading Understanding and Memory Program, employs this approach to parsing. FRUMP skims articles rather than reading them for detail. The program works on the relatively unconstrained domain of news articles. It routinely understands stories it has never before seen. The program's success is largely due to its radically different approach to parsing.
A Cognitive Model of Planning*
Authors: Hayes‐Roth Barbara , Hayes‐Roth Frederick
Published: October 2005

This paper presents a cognitive model of the planning process. The model generalizes the theoretical architecture of the Hearsay‐ll system. Thus, it assumes that planning comprises the activities of a variety of cognitive “specialists.” Each specialist can suggest certain kinds of decisions for incorporation into the plan in progress. These include decisions about: (a) how to approach the planning problem; (b) what knowledge bears on the problem; (c) what kinds of actions to try to plan; (d) what specific actions to plan; and (e) how to allocate cognitive resources during planning. Within each of these categories, different specialists suggest decisions at different levels of abstraction. The activities of the various specialists are not coordinated in any systematic way. Instead, the specialists operate opportunistically, suggesting decisions whenever promising opportunities arise. The paper presents a detailed account of the model and illustrates its assumptions with a “thinking aloud” protocol. It also describes the performance of a computer simulation of the model. The paper contrasts the proposed model with successive refinement models and attempts to resolve apparent differences between the two points of view.
Differences Between Belief and Knowledge Systems*
Authors: Abelson Robert P.
Published: October 2005

Seven features which in practice seem to differentiate belief systems from knowledge systems are discussed. These are: nonconsensuality, “existence beliefs,” alternative worlds, evaluative components, episodic material, unboundedness, and variable credences. Each of these features gives rise to challenging representation problems. Progress on any of these problems within artificial intelligence would be helpful in the study of knowledge systems as well as belief systems, inasmuch as the distinction between the two types of systems is not absolute.
Meta‐Planning: Representing and Using Knowledge About Planning in Problem Solving and Natural Language Understanding*
Authors: Wilensky Robert
Published: October 2005

This paper is concerned with those elements of planning knowledge that are common to both understanding someone else's plan and creating a plan for one's own use. This planning knowledge can be divided into two bodies: Knowledge about the world, and knowledge about the planning process itself. Our interest here is primarily with the latter corpus. The central thesis is that much of the knowledge about the planning process itself can be formulated in terms of higher‐level goals and plans called meta‐goals and meta‐plans. These entities can then be used by the same understanding and planning mechanisms that process ordinary goals and plans. However, the meta‐planning knowledge now enables these mechanisms to handle much more complicated situations in a uniform manner.

Systems based on meta‐planning would have a number of advantages over existing problem solving and understanding systems. The same knowledge could be shared by both a planner and understander, and both would be able to handle complex situations elegantly. In addition, in planning, the use of meta‐planning has several advantages over more traditional methods involving constraints or critics. Meta‐planning allows the full power of a problem solver to be applied to situations that are generally amenable only to special purpose processing. In addition, meta‐planning facilitates the representation of some situations that are difficult to express otherwise. We have begun to introduce meta‐planning knowledge into two systems: PAM, a story understanding program, and PANDORA, a problem solving and plannin̈g system.
Expertise and Error in Diagnostic Reasoning*
Authors: Johnson Paul E. , Duran Alica S. , Hassebrock Frank , Moller James , Prietula Michael , Feltovich Paul J. , Swanson David B.
Published: October 2005

An investigation is presented in which a computer simulation model (DIAGNOSER) is used to develop and test predictions for behavior of subjects in a task of medical diagnosis. The first experiment employed a process‐tracing methodology in order to compare hypothesis generation and evaluation behavior of DIAGNOSER with individuals at different levels of expertise (students, trainees, experts). A second experiment performed with only DIAGNOSER identified conditions under which errors in reasoning in the first experiment could be related to interpretation of specific data items. Predictions derived from DIAGNOSER's performance were tested in a third experiment with a new sample of subjects. Data from the three experiments indicated that (1) form of diagnostic reasoning was similar for all subjects trained in medicine and for the simulation model, (2) substance of diagnostic reasoning employed by the simulation model was parable with that of the more expert subjects, and (3) errors in subjects' reasoning were attributable to deficiencies in disease knowledge and the interpretation of specific patient data cues predicted by the simulation model.
Plot Units and Narrative Summarization*
Authors: Lehnert Wendy G.
Published: October 2005

In order to summarize a story, it is necessary to access a high level analysis of the story that highlights its central concepts. A technique of memory representation based on plot units appears to provide a rich foundation for such an analysis. Plot units are conceptual structures that overlap with each other when a narrative is cohesive. When overlapping intersections between plot units are interpreted as arcs in a graph of plot units, the resulting graph encodes the plot of the story. Structural features of the graph then reveal which concepts are central to the story, and which concepts are peripheral. Plot unit analysis is currently being investigated as a processing strategy for narrative summarization by both computer simulation and psychological experiments.
Structure and Strategy in Image Generation*
Authors: Farah Martha J. , Kosslyn Stephen M.
Published: October 2005

Two experiments were conducted to test a prediction of the Kosslyn & Shwartz computer simulation model of mental image processing. According to this model, more complex images require more time to form because parts are placed sequentially, and larger images require more time to form than smaller ones because more parts are placed. If these accounts are correct, then the advantage of forming a small image (i.e., one that seems to subtend a smaller visual angle) should be greater for more complex objects because the difference in number of parts imaged at the two sizes will be greater than with simpler objects. This prediction was confirmed only when subjects were not motivated to form highly elaborated images at small sizes. When subject tried to include all details, it actually took longest to form images of complex objects at small sizes. Both of these results support the central assumption of the Kosslyn‐Shwartz model, namely the existence of a fixed resolution analog spatial medium.
Generalization From Natural Language Text*
Authors: Lebowitz Michael
Published: October 2005

Generalization and memory are part of natural language understanding. This paper describes a model of generalization that is part of a system for language understanding. the Integrated Partial Parser (IPP). The generalization process includes the retrieval of relevant examples from long‐term memory so that the concepts to be created can be determined when new stories are read. Generalizations are analyzed as to their critical parts and evaluated in light of later evidence. The knowledge structures used and a number of examples of the system in operation are presented.
Sources of Difficulty in Understanding Newtonian Dynamics*
Authors: White Barbara Y.
Published: October 2005

A series of force and motion problems was presented to 40 high school science students. The results revealed that the majority of the students only partially understood the formalisms of Newtonian physics. Many had difficulty determining the effect that a force would have on an object' speed of motion and many neglected to take into account thecurrent speed of motion when attempting to predict how a force would alter an obiect's direction of motion. The students' justifications for their erroneous answers suggest that they utilize diverse, and often inconsistent, ideas when solving force and motion problems. These include (a) faulty beliefs about force and motion which have been derived from living in a world where unseen frictional forces operate; (b) partially understood examples from physics class; and (c) knowledge of the properties of scalar arithmetic, some of which do not transfer to vector arithmetic. The students thus employ components of their knowledge, which seem relevant to the solution of force and motion problems, but which often have properties that conflict with the implications of Newton's laws of motion.
A Parallel‐Process Model of Mental Rotation*
Authors: Funt Brian V.
Published: October 2005

It is argued that some of the phenomena identified with analog processes by Shepard can be understood as resulting from a parallel‐process algorithm running on a processor having many individual processing elements and a restricted communication structure. In particular, an algorithm has been developed and implemented which models human behavior on Shepard's object rotation and comparison task. The algorithm exhibits computation times which increase linearly with the angle of rotation. Shepard found a similar linear function in his experiments with human subjects. In addition, the intermediate states of the computation are such that if the rotation process were to be interrupted at any point, the object representation would correspond to that of the actual object at a position along the rotation trajectory. The computational model presented here is governed by three constraining assumptions: (a) that it be parallel: (b) that the communication between processors be restricted to immediate neighbors: (c) that the object representation be distributed across a large fraction of the available processors. A method of diagnosing the correct axis of rotation is also presented.
Discrimination Nets as Psychological Models*
Authors: Barsalou Lawrence W. , Bower Gordon H.
Published: October 2005

Simulations of human cognitive processes often employ discrimination nets to model the access of permanent memory. We consider two types of discrimination nets—EPAM and positive‐proper‐only nets—and argue that they have insufficient psychological validity. Their deficiencies arise from negative properties, insufficient sensitivity to the discriminativeness of properties, extreme sensitivity to missing or incorrect properties, inefficiency in representing multiple knowledge domains, and seriality. We argue that these deficiencies stem from a high degree of test contingency in utilizing property information during acquisition and memory search. Discrimination nets are compared to other models that have less or no test contingency (e.g., PANDEMONIUM) and that thereby avoid the problems of discrimination nets. We propose that understanding test contingency and discovering psychologically valid ways to implement it will be central to understanding and simulating memory indexing in human cognition.
Empirical Evidence for Narrative Structure*
Authors: Gee James Paul , Grosjean Francois
Published: October 2005

Three experimental tasks—spontaneous telling of a story, reading, and parsing the story—were used to determine whether empirical data reflect the narrative structure of stories and can be predicted by a plot unit analysis of the stories (Lehnert, 1981). It was found that spontaneous pause durations at sentence breaks were highly correlated with the importance of these breaks as predicted theoretically. Only low correlations were obtained, however, when reading pause durations were correlated with the model. As for parsing values, the value of the correlation coefficients depended on whether stories had sufficient superficial linguistic cues to help the subjects in parsing. It was concluded that spontaneous pausing not only reflects the narrative structure of stories, but can be used as a guide to constructing theories of narrative structure as well as for deciding between competing theories.
Recruitment of CRABS CLAW to promote nectary development within the eudicot clade
Authors: Lee Ji-Young , Baum Stuart F. , Oh Sang-Hun , Jiang Cai-Zhong , Chen Jen-Chih , Bowman John L.
Published: October 2005

Nectaries are secretory organs that are widely present in flowering plants that function to attract floral pollinators. Owing to diversity in nectary positions and structures, they are thought to have originated multiple times during angiosperm evolution, with their potential contribution to the diversification of flowering plants and pollinating animals being considerable. We investigated the genetic basis of diverse nectary forms in eudicot angiosperm species using CRABS CLAW (CRC), a gene required for nectaries in Arabidopsis. CRC expression is conserved in morphologically different nectaries from several core eudicot species and is required for nectary development in both rosids and asterids,two major phylogenetic lineages of eudicots. However, in a basal eudicot species, no evidence of CRC expression in nectaries was found. Considering the phylogenetic distribution of nectary positions and CRC expression analyses in eudicots, we propose that diverse nectaries in core eudicots share conserved CRC gene regulation, and that derived nectary positions in eudicots have altered regulation of CRC. As the ancestral function of CRC lies in the regulation of carpel development, it may have been co-opted as a regulator of nectary development within the eudicots, concomitant with the association of nectaries with reproductive organs in derived lineages.
Developmental analysis and squamous morphogenesis of the peripodial epithelium in Drosophila imaginal discs
Authors: McClure Kimberly D. , Schubiger Gerold
Published: October 2005

Imaginal discs of Drosophila provide an excellent system with which to study morphogenesis, pattern formation and cell proliferation in an epithelium. Discs are sac-like in structure and are composed of two epithelial layers: an upper peripodial epithelium and lower disc proper. Although development of the disc proper has been studied extensively in terms of cell proliferation, cell signaling mechanisms and pattern formation, little is known about these same processes in the peripodial epithelium. We address this topic by focusing on morphogenesis, compartmental organization, proliferation and cell lineage of the PE in wing, second thoracic leg (T2) and eye discs. We show that a subset of peripodial cells in different imaginal discs undergo a cuboidal-to-squamous cell shape change at distinct larval stages. We find that this shape change requires both Hedgehog and Decapentapelagic, but not Wingless, signaling. Additionally, squamous morphogenesis shifts the anteroposterior (AP) compartment boundary in the peripodial epithelium relative to the stationary AP boundary in the disc proper. Finally, by lineage tracing cells in the PE, we surprisingly find that peripodial cells are displaced into the disc proper during larval development and this movement leads to Ubx repression.
Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina
Authors: Wang Yaping , Dakubo Gabriel D. , Thurig Sherry , Mazerolle Chantal J. , Wallace Valerie A.
Published: October 2005

The timing of cell cycle exit and temporal changes in the developmental competence of precursor cells are key components for the establishment of the normal complement of cell types in the mammalian retina. The identity of cell extrinsic cues that control these processes is largely unknown. We showed previously in mouse retina that sonic hedgehog (Shh) signalling from retinal ganglion cells (RGCs) to retinal precursor cells (RPC) is required for the establishment of normal retinal organization. Here, we show that conditional ablation of Shh expression in the peripheral mouse results in a depletion of the RPC pool, owing to precocious cell-cycle exit and neuronal differentiation. These changes were correlated with the downregulation of cyclin D1 and Hes1 gene expression. Shh inactivation also results in an increase in RGC number owing to a bias of RPC towards RGC production. In contrast to zebrafish, where Shh signalling drives cell cycle exit and RGC development, our findings indicate that in the mouse retina Shh signalling is required to maintain RPC proliferation and to control the timing of RGC development.
Managing health inequalities locally: a baseline survey of primary care trusts' experience with health equity audit in the implementation year
Authors: Aspinall Peter J , Jacobson Bobbie
Published: October 2005

Health equity audit (HEA), a pragmatic policy tool to ensure that services and resources are focused on issues that have the highest impact on health inequalities, has now become embedded in the national strategy to tackle these inequalities through a new mandatory requirement that primary care trusts (PCTs) conduct one such audit annually. This study aimed to assess their experience through a national baseline survey in 2004, all PCTs ( n = 303) being electronically mailed a questionnaire with non-respondent follow-up. Replies were received from 132 PCTs (44%), a representative sample of PCT diversity, most of whom had completed only a few steps in the audit cycle. Audit topics (most frequently coronary heart disease, smoking cessation, and access issues) and dimensions of inequity (mainly area and deprivation) were agreed through only limited engagement with local strategic partnerships. Local public health networks and multiagency teams were infrequent partners in undertaking the HEA. Most PCTs wanted comparator data, good practice examples, and specific methodological expertise. While significant progress has been made, this survey shows only limited use of HEA as a tool for multisectoral use by PCTs in partnership with others and a focus on intra-PCT comparisons at the expense of those with a wider pool of 'look-a-likes'.
An analysis of high-cost users at an Australian public health service organization
Authors: Heslop Liza , Athan Dean , Gardner Brendon , Diers Donna , Poh Boon Choo
Published: October 2005

High-cost users generate extremely high costs when compared with average users in the same diagnostic-related group (DRG). They represent a major financial loss for a health service organization. The research was conducted using an area health service patient database for online analytical processing to produce descriptive statistics and graphs of 'high-cost' and 'non-high-cost users'. Trends and patterns were identified across key variables derived from clinical, financial and operational categories. The main results are:

• 20% of costs are spent by 3% of the population;

• elective admission is higher in the high-cost group;

• tracheostomy has the most number of cases and is the most expensive DRG;

• LOS is mostly longer for complex cases however, high costs can be attributed to other factors.

In conclusion, these findings are potentially useful to patients, medical staff, management and health service decision-makers. The limitation of this study is the exclusion of profitability.
Can we use routine data to evaluate organizational change? Lessons from the evaluation of business process re-engineering in a UK teaching hospital
Authors: Brennan A , Sampson F , Deverill M
Published: October 2005

Objective: To review and critically evaluate a multidisciplinary independent evaluation of business process re-engineering within a UK hospital using routine data.

Methods: Routine data measures of hospital cost efficiency are used to compare rates of changes at Leicester Royal Infirmary (LRI) with a 'peer group' of 22 teaching hospitals and to ascertain changes attributable to re-engineering. Different adjustment factors are quantified and the robustness of individual measures discussed. In addition to providing context to the quantitative primary research and the qualitative research on change management, service performance and quality indicators not captured in overall efficiency measures are assessed using detailed routine data measures.

Results: LRI is one of the most efficient teaching hospitals in England and continued improvement during re-engineering is shown to be at a faster rate than the peer group average, although attribution of changes is difficult. Lack of availability and inconsistency of data for support services meant that many re-engineering initiatives are not quantifiable using routine data measures.

Conclusions: When combining different measures, routine data is a valuable tool in evaluating organizational change initiatives. However, use in future evaluations would require consistent benchmarking of routine data.
The relationship between income and performance indicators in general practice: a cross-sectional study
Authors: Ashworth M , Armstrong D , de Freitas J , Boullier G , Garforth J , Virji A
Published: October 2005

Objective: To explore the relationship between the income of general practitioners (GPs) and the performance characteristics of their practices.

Design: Cross-sectional survey.

Setting: All practices ( n = 166) in an inner city health authority, two years before the introduction of the new GP contract in April 2004 were studied.

Main outcome measures: True income per GP was unavailable to us. Instead, the proxy measure - superannuable pay - was calculated (gross eligible income per GP minus the national average sum for GP expenses). Practice staff funding figures were also obtained. These two financial indicators were compared with practice characteristics and performance indicators.

Results: Data were available from 151 out of 166 practices. Based on regression analysis, larger list sizes and higher practice staff budgets predicted 31% of the variation in GP income (standardized β = 0.66, P < 0.001; β = 0.19, P = 0.02; respectively). Higher staff budgets were independently associated with better cervical smear and two-year-old vaccination rates (standardized β = 0.24, P < 0.01; β = 0.18, P = 0.03; respectively). No association was demonstrated between performance indicators and income.

Conclusion: Under the previous contract, GPs were able to maximize their income by taking on more patients, whereas achievement of performance targets had very little impact on overall income. The opportunity costs of pursuing higher-quality care might have outweighed the modest financial rewards attached to performance targets. Provided rewards for good-quality care are sufficiently high, the new GP contract is likely to tip the balance in favour of generating earnings by improving the quality of clinical care. To deliver this care, as measured by available performance indicators, our findings imply that a greater investment in practice staff will be needed.
The proximity heuristic in judgments of accident probabilities
Authors: Teigen Karl Halvor
Published: October 2005

In daily life, probabilities are often assessed informally through the perceived distance to a target event. Accident probabilities are believed to be high when a disastrous outcome appears to be close. This proximity heuristic can lead to exaggerated p(death) estimates in risky situations (Experiment 2), and sometimes higher probabilities for death after near‐accidents than after actual accidents (Experiment 3 and 4). Near‐accidents are also believed to be equally good, or better, predictors of future disasters than actual accidents, despite being less serious and more frequent (Experiment 5). The proximity heuristic influences the way people talk about their own and other people's chances (Experiment 1), and how they prepare to avoid (or, if necessary, to produce) a disastrous outcome (Experiment 6).
The link between composition and balance in masterworks vs. paintings of lower artistic quality
Authors: Vartanian Oshin , Martindale Colin , Podsiadlo Jacob , Overbay Shane , Borkum Jonathan
Published: October 2005

In painting, composition is commonly defined as the two‐dimensional arrangement of elements within the canvas. Each element is considered to have a perceptual weight. The arrangement of these weighted elements determines how balanced a painting is. It has been suggested that due to superior composition, masterworks may be more balanced than works of lower artistic quality. We tested this hypothesis by instructing our participants to rate masterworks and selections of lower artistic quality on balance. This hypothesis was not supported. Second, it has been suggested that rearranging elements within a painting may have a more detrimental effect on composition (and by extension balance) in masterworks than in selections of lower artistic quality. This view associates works of higher artistic quality with visual rightness, thereby predicting that compositional change would be more likely to cause deviations from a visually right state in masterworks. We tested this hypothesis by displacing an element within each painting to a different location, and measuring the effect on balance. In accordance with recent findings in the literature, we also took into account the severity of the compositional alterations. The results demonstrated that compositional alteration affected balance ratings equally across masterworks and selections of lower artistic quality. These results demonstrate that, although balance is a function of compositional structure, balance on its own is not sufficient to distinguish between works of varying artistic quality. To the extent that balance is considered a function of composition, the results suggest that masterworks are distinguished from works of lower artistic quality for reasons other than solely composition.
Terror threat perception and its consequences in contemporary Britain
Authors: Goodwin Robin , Willson Michelle , Stanley Gaines
Published: October 2005

The terrorist attacks of 9/11, and subsequent terrorist acts around the world, have alerted social psychologists to the need to examine the antecedents and consequences of terrorist threat perception. In these two studies, we examined the predictive power of demographic factors (age, gender, location), individual values and normative influences on threat perception and the consequences of this perception for behavioural change and close relationships. In Study 1 (N=100), gender, benevolence values and normative influences were all correlates of threat perception, whilst sense of personal threat was correlated with increased contact with friends and family. In Study 2 (N=240) age, gender, location, and the values of openness to change and hedonism, all predicted threat perception, which, in turn, predicted behavioural change and relationship contact. Such findings point to the important role social psychologists should play in understanding responses to these new terrorist threats.
Visual Selection and Posterior Parietal Cortex: Effects of Repetitive Transcranial Magnetic Stimulation on Partial Report Analyzed by Bundesen's Theory of Visual Attention
Authors: Hung June , Driver Jon , Walsh Vincent
Published: October 2005

Posterior parietal cortex (PPC) may contribute to visual selection by exerting top-down influences on visual processing. To seek direct evidence for this, we used 10 Hz repetitive transcranial magnetic stimulation (rTMS) over right or left PPC in nine healthy volunteers during a partial (selective) report task that allows quantitative assessment of top-down control and other parameters. Participants reported digits in a relevant color (“targets”) but not those in an irrelevant color (“nontargets”) from a brief masked display, in which a target could appear alone or together with an accompanying item (nontarget or target) in the same or opposite hemifield. Generally, a given target is identified better when presented with a nontarget than with another target, indicating top-down selection of task-relevant targets; this applied here with no rTMS or left PPC rTMS. However, rTMS over the right PPC changed the performance pattern. A left target no longer impeded report of a right target more strongly than did a left nontarget, whereas the greater impact of a right target than a right nontarget in disrupting report of a left target was increased. Formal analysis in terms of Bundesen's (1990) theory of visual attention indicated that right PPC rTMS diminished top-down control for the left hemifield while enhancing this for the right hemifield, particularly for bilateral two-item displays. These findings indicate a role for right PPC in top-down spatial selection, which applies even when the target is defined by a nonspatial property (here color).
Differential Maturation of GABA Action and Anion Reversal Potential in Spinal Lamina I Neurons: Impact of Chloride Extrusion Capacity
Authors: Cordero-Erausquin Matilde , Coull Jeffrey A. M. , Boudreau Dominic , Rolland Matthias , Koninck Yves De
Published: October 2005

A deficit in inhibition in the spinal dorsal horn has been proposed to be an underlying cause of the exaggerated cutaneous sensory reflexes observed in newborn rats. However, the developmental shift in transmembrane anion gradient, potentially affecting the outcome of GABAAtransmission, was shown to be completed within 1 week after birth in the spinal cord, an apparent disparity with the observation that reflex hypersensitivity persists throughout the first 2-3 postnatal weeks.

To further investigate this issue, we used several approaches to assess the action of GABA throughout development in spinal lamina I (LI) neurons. GABA induced an entry of extracellular calcium in LI neurons from postnatal day 0 (P0) to P21 rats, which involved T- and N-type voltage-gated calcium channels. Gramicidin perforated-patch recordings revealed that the shift in anion gradient was completed by P7 in LI neurons. However, high chloride pipette recordings demonstrated that these neurons had not reached their adult chloride extrusion capacity by P10-P11. Simultaneous patch-clamp recordings and calcium imaging revealed that biphasic responses to GABA, consisting of a primary hyperpolarization followed by a rebound depolarization, produced a rise in [Ca2+]i. Thus, even ifEanionpredicts GABAA-induced hyperpolarization from rest, a low chloride extrusion capacity can cause a rebound depolarization and an ensuing rise in [Ca2+]i.

We demonstrate that GABA action in LI neurons matures throughout the first 3 postnatal weeks, therefore matching the time course of maturation of withdrawal reflexes. Immature spinal GABA signaling may thus contribute to the nociceptive hypersensitivity in infant rats.
Proximal Persistent Na+Channels Drive Spike Afterdepolarizations and Associated Bursting in Adult CA1 Pyramidal Cells
Authors: Yue Cuiyong , Remy Stefan , Su Hailing , Beck Heinz , Yaari Yoel
Published: October 2005

In many principal brain neurons, the fast, all-or-none Na+spike initiated at the proximal axon is followed by a slow, graded afterdepolarization (ADP). The spike ADP is critically important in determining the firing mode of many neurons; large ADPs cause neurons to fire bursts of spikes rather than solitary spikes. Nonetheless, not much is known about how and where spike ADPs are initiated. We addressed these questions in adult CA1 pyramidal cells, which manifest conspicuous somatic spike ADPs and an associated propensity for bursting, using sharp and patch microelectrode recordings in acutely isolated hippocampal slices and single neurons. Voltage-clamp commands mimicking spike waveforms evoked transient Na+spike currents that declined quickly after the spike but were followed by substantial sustained Na+spike aftercurrents. Drugs that blocked the persistent Na+current (INaP), markedly suppressed the sustained Na+spike aftercurrents, as well as spike ADPs and associated bursting. Ca2+spike aftercurrents were much smaller, and reducing them had no noticeable effect on the spike ADPs. Truncating the apical dendrites affected neither spike ADPs nor the firing modes of these neurons. Application ofINaPblockers to truncated neurons, or their focal application to the somatic region of intact neurons, suppressed spike ADPs and associated bursting, whereas their focal application to distal dendrites did not. We conclude that the somatic spike ADPs are generated predominantly by persistent Na+channels located at or near the soma. Through this action, proximalINaPcritically determines the firing mode and spike output of adult CA1 pyramidal cells.
Cyclin-Dependent Kinase 5 Is Essential for Neuronal Cell Cycle Arrest and Differentiation
Authors: Cicero Samantha , Herrup Karl
Published: October 2005

Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase with significant homology to cell cycle-related Cdks but is not believed to be active in a typical cell cycle. In Cdk5-deficient embryos and Cdk5 chimeras, migration and survival of postmitotic neurons is compromised in a cell-autonomous manner. In the present study, we show that loss of Cdk5 leads to both failure of neuronal differentiation and loss of cell cycle control. Using specific cytoskeletal proteins as indices of neuronal differentiation, we find that Cdk5-deficient neurons are significantly arrested or delayed in their developmental program bothin vivoandin vitro. For example, immunocytochemistry of embryonic day 16 (E16) cortex reveals that the expression of microtubule-associated protein 2c (Map-2c), a marker of mature neurons, is nearly absent inCdk5-/-cells that have migrated to the cortical plate while these same cells continue to express nestin. Similarly,in vitro, Map-2-positive cells are rare in cultures from E16Cdk5-/-embryos. Cell cycle control is also deficient inCdk5-/-cells.In vivo, neurons engaged in cell cycle activities are found in the cortical plate, and,in vitro, class III β-tubulin-positive cells continue to label with bromodeoxyuridine even after 5 d of incubation. Transfection of a wild-type Cdk5 construct reveals that cell cycle control can be regained inCdk5-/-cells by overexpression of Cdk5. These data indicate that Cdk5 is necessary for both neuronal differentiation and cell cycle inhibition.
The Role of Sensory Network Dynamics in Generating a Motor Program
Authors: Levi Rafael , Varona Pablo , Arshavsky Yuri I. , Rabinovich Mikhail I. , Selverston Allen I.
Published: October 2005

Sensory input plays a major role in controlling motor responses during most behavioral tasks. The vestibular organs in the marine molluskClione, the statocysts, react to the external environment and continuously adjust the tail and wing motor neurons to keep the animal oriented vertically. However, we suggested previously that during hunting behavior, the intrinsic dynamics of the statocyst network produce a spatiotemporal pattern that may control the motor system independently of environmental cues. Once the response is triggered externally, the collective activation of the statocyst neurons produces a complex sequential signal. In the behavioral context of hunting, such network dynamics may be the main determinant of an intricate spatial behavior. Here, we show that (1) during fictive hunting, the population activity of the statocyst receptors is correlated positively with wing and tail motor output suggesting causality, (2) that fictive hunting can be evoked by electrical stimulation of the statocyst network, and (3) that removal of even a few individual statocyst receptors critically changes the fictive hunting motor pattern. These results indicate that the intrinsic dynamics of a sensory network, even without its normal cues, can organize a motor program vital for the survival of the animal.
Lesions of the Basal Amygdala Block Expression of Conditioned Fear But Not Extinction
Authors: Anglada-Figueroa David , Quirk Gregory J.
Published: October 2005

Although the role of the amygdala in acquisition of conditioned fear is well established, there is debate concerning the intra-amygdala circuits involved. The lateral nucleus of the amygdala (LA) is thought to be an essential site of plasticity in fear conditioning. The LA has both direct and indirect [via the basal nuclei; basal amygdala (BA)] projections to the central nucleus (Ce) of the amygdala, an essential output for fear behaviors. Lesions of the LA or Ce prevent acquisition of conditioned freezing to a conditioned stimulus, but BA lesions do not, suggesting that the BA is not normally involved in fear conditioning. If true, posttraining BA lesions should also have no effect. Replicating previous studies, we found that rats given electrolytic BA lesions before training acquired conditioned fear normally. They also showed normal long-term retention and extinction of conditioned fear. Unexpectedly, BA lesions made after training completely blocked expression of conditioned fear. Despite this deficit, lesioned rats were able to learn a new tone-shock association. Thus, although the LA-Ce system is sufficient for fear acquisition in the absence of the BA, it is not sufficient when the BA is present, suggesting that the BA is an important site of plasticity in fear conditioning. The pattern of lesion deficits we observed (after but not before training) might be explained by homeostatic mechanisms that balance plasticity over multiple inputs, regulating the influence of the BA and LA onto Ce output neurons.
Dysfunction of Synaptic Inhibition in Epilepsy Associated with Focal Cortical Dysplasia
Authors: Calcagnotto Maria Elisa , Paredes Mercedes F. , Tihan Tarik , Barbaro Nicholas M. , Baraban Scott C.
Published: October 2005

Focal cortical dysplasia (FCD) is a common and important cause of medically intractable epilepsy. In patients with temporal lobe epilepsy and in several animal models, compromised neuronal inhibition, mediated by GABA, contributes to seizure genesis. Although reduction in GABAergic interneuron density has been reported in FCD tissue samples, there is little available information on the resulting physiological changes in synaptic inhibition and the potential contribution of these changes to epileptogenesis in the dysplastic human brain. Using visualized whole-cell patch-clamp recordings from identified neurons in tissue slices obtained from patients with FCD, we demonstrate that GABAA-receptor-mediated inhibition is substantially altered in regions of dysplasia. These alterations include a significant reduction in IPSC frequency and a potentially compensatory decrease in transporter-mediated GABA reuptake function; the latter is marked by a significant increase in the decay-time constant for evoked and spontaneous IPSCs and a lack of effect of the GABA transport-inhibitor 1-[2([(diphenylmethylene)imino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride on IPSC kinetics. Immunohistochemical staining revealed a scattering of GABAergic interneurons across dysplastic cortex and striking reductions in GABA transporter expression. Together, these results suggest that profound alterations in GABA-mediated synaptic inhibition play an essential role in the process of epileptogenesis in patients with FCD.
Vulnerability of Dentate Granule Cells to Disruption of Arc Expression in Human Amyloid Precursor Protein Transgenic Mice
Authors: Palop Jorge J. , Chin Jeannie , Bien-Ly Nga , Massaro Catherine , Yeung Bertrand Z. , Yu Gui-Qiu , Mucke Lennart
Published: October 2005

Activity-induced expression of Arc is necessary for maintenance of long-term potentiation and for memory consolidation. In transgenic (TG) mice with neuronal production of human amyloid precursor protein (hAPP) and hAPP-derived amyloid-β (Aβ) peptides, basalArcexpression was reduced primarily in granule cells of the dentate gyrus. After exploration of a novel environment,Arcexpression in these neurons was unaltered in hAPP mice but increased markedly in nontransgenic controls. Other TG neuronal populations showed no or only minor deficits in Arc expression, indicating a special vulnerability of dentate granule cells. The phosphorylation states of NR2B and ERK1/2 were reduced in the dentate gyrus of hAPP mice, suggesting attenuated activity in NMDA-dependent signaling pathways that regulate synaptic plasticity as well as Arc expression. Arc reductions in hAPP mice correlated with reductions in the actin-binding protein α-actinin-2, which is located in dendritic spines and, like Arc, fulfills important functions in excitatory synaptic activity. Reductions in Arc and α-actinin-2 correlated tightly with reductions in Fos and calbindin, shown previously to reflect learning deficits in hAPP mice. None of these alterations correlated with the extent of plaque formation, suggesting a plaque-independent mechanism of hAPP/Aβ-induced neuronal deficits. The brain region-specific depletion of factors that participate in activity-dependent modification of synapses may critically contribute to cognitive deficits in hAPP mice and possibly in humans with Alzheimer's disease.
Modulation of Presynaptic Plasticity and Learning by the H-ras/Extracellular Signal-Regulated Kinase/Synapsin I Signaling Pathway
Authors: Kushner Steven A. , Elgersma Ype , Murphy Geoffrey G. , Jaarsma Dick , van Woerden Geeske M. , Hojjati Mohammad Reza , Cui Yijun , LeBoutillier Janelle C. , Marrone Diano F. , Choi Esther S. , De Zeeuw Chris I. , Petit Ted L. , Pozzo-Miller Lucas , Silva Alcino J.
Published: October 2005

Molecular and cellular studies of the mechanisms underlying mammalian learning and memory have focused almost exclusively on postsynaptic function. We now reveal an experience-dependent presynaptic mechanism that modulates learning and synaptic plasticity in mice. Consistent with a presynaptic function for endogenous H-ras/extracellular signal-regulated kinase (ERK) signaling, we observed that, under normal physiologic conditions in wild-type mice, hippocampus-dependent learning stimulated the ERK-dependent phosphorylation of synapsin I, and MEK (MAP kinase kinase)/ERK inhibition selectively decreased the frequency of miniature EPSCs. By generating transgenic mice expressing a constitutively active form of H-ras (H-rasG12V), which is abundantly localized in axon terminals, we were able to increase the ERK-dependent phosphorylation of synapsin I. This resulted in several presynaptic changes, including a higher density of docked neurotransmitter vesicles in glutamatergic terminals, an increased frequency of miniature EPSCs, and increased paired-pulse facilitation. In addition, we observed facilitated neurotransmitter release selectively during high-frequency activity with consequent increases in long-term potentiation. Moreover, these mice showed dramatic enhancements in hippocampus-dependent learning. Importantly, deletion of synapsin I, an exclusively presynaptic protein, blocked the enhancements of learning, presynaptic plasticity, and long-term potentiation. Together with previous invertebrate studies, these results demonstrate that presynaptic plasticity represents an important evolutionarily conserved mechanism for modulating learning and memory.
Identification of a New Neuropeptide Precursor Reveals a Novel Source of Extrinsic Modulation in the Feeding System ofAplysia
Authors: Proekt Alex , Vilim Ferdinand S. , Alexeeva Vera , Brezina Vladimir , Friedman Allyson , Jing Jian , Li Lingjun , Zhurov Yuriy , Sweedler Jonathan V. , Weiss Klaudiusz R.
Published: October 2005

TheAplysiafeeding system is advantageous for investigating the role of neuropeptides in behavioral plasticity. One family ofAplysianeuropeptides is the myomodulins (MMs), originally purified from one of the feeding muscles, the accessory radula closer (ARC). However, two MMs, MMc and MMe, are not encoded on the only known MM gene. Here, we identify MM gene 2 (MMG2), which encodes MMc and MMe and four new neuropeptides. We use matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to verify that these novel MMG2-derived peptides (MMG2-DPs), as well as MMc and MMe, are synthesized from the precursor. Using antibodies against the MMG2-DPs, we demonstrate that neuronal processes that stain for MMG2-DPs are found in the buccal ganglion, which contains the feeding network, and in the buccal musculature including the ARC muscle. Surprisingly, however, no immunostaining is observed in buccal neurons including the ARC motoneurons.In situhybridization reveals only fewMMG2-expressing neurons that are mostly located in the pedal ganglion. Using immunohistochemical and electrophysiological techniques, we demonstrate that some of these pedal neurons project to the buccal ganglion and are the likely source of the MMG2-DP innervation of the feeding network and musculature. We show that the MMG2-DPs are bioactive both centrally and peripherally: they bias egestive feeding programs toward ingestive ones, and they modulate ARC muscle contractions. The multiple actions of the MMG2-DPs suggest that these peptides play a broad role in behavioral plasticity and that the pedal-buccal projection neurons that express them are a novel source of extrinsic modulation of the feeding system ofAplysia.