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Synaptic inputs to cortical neurons are highly structured in adult sensory systems, such that neighboring synapses along dendrites are activated by similar stimuli. This organization of synaptic inputs, called synaptic clustering, is required for high-fidelity signal processing, and clustered synapses can already be observed before eye opening. However, how clustered inputs emerge during development is unknown. Here, we employed concurrentin vivowhole-cell patch clamp and dendritic calcium imaging to map spontaneous synaptic inputs to dendrites of layer 2/3 neurons in the mouse primary visual cortex during the second postnatal week until eye opening. We find that the number of functional synapses and the frequency of transmission events increase several fold during this developmental period. At the beginning of the second postnatal week, synapses assemble specifically in confined dendritic segments, whereas other segments are devoid of synapses. By the end of the second postnatal week, just before eye-opening, dendrites are almost entirely covered by domains of co-active synapses. Finally, co-activity with their neighbor synapses correlates with synaptic stabilization and potentiation. Thus, clustered synapses form in distinct functional domains presumably to equip dendrites with computational modules for high-capacity sensory processing when the eyes open.

This study uses generalized additive models to identify and analyze nonlinear relationships between accounting-based and market-based independent variables and how these affect bankruptcy predictions. Specifically, it examines the independent variables that Altman (J Financ 23:589–609, 1968; Predicting financial distress of companies. Revisiting the Z-score and ZETA® models. Working paper, 2000) and Campbell et al. (J Financ 63:2899–2939, 2008) used and analyzes what specific form these nonlinear relationships take. Drawing on comprehensive data on listed U.S. companies, we show empirically that the bankruptcy prediction is influenced by statistically and economically relevant nonlinear relationships. Our results indicate that taking into account these nonlinear relationships improves significantly several statistical validity measures. We also use a validity measure that is based on the profitability of the bankruptcy prediction models in the context of credit scoring. The findings demonstrate that taking into account nonlinear relationships can substantially increase the discriminatory power of bankruptcy prediction models.

The internal audit function (IAF) has become one of the main pillars of good corporate governance. Empirical findings show that the size of the IAF varies considerably across companies. This study analyzes the relationships between selected company characteristics as determinants of intra-company information asymmetries and the size of the IAF as an indicator of intra-company monitoring. We test these relationships by analyzing comprehensive survey data obtained from chief audit executives from 283 Austrian, German, and Swiss companies. Using a nonparametric regression approach, we identify significant nonlinear relationships between company characteristics and IAF size. The empirical analysis identifies threshold levels for several metric company characteristics, such as the number of employees and the number of subsidiaries, whose relationships with the size of the IAF change its intensity.

Developing neurons form synapses at a high rate. Synaptic transmission is very energy-demanding and likely requires ATP production by mitochondria nearby. Mitochondria might be targeted to active synapses in young dendrites, but whether such motility regulation mechanisms exist is unclear. We investigated the relationship between mitochondrial motility and neuronal activity in the primary visual cortex of young mice in vivo and in slice cultures. During the first 2 postnatal weeks, mitochondrial motility decreases while the frequency of neuronal activity increases. Global calcium transients do not affect mitochondrial motility. However, individual synaptic transmission events precede local mitochondrial arrest. Pharmacological stimulation of synaptic vesicle release, but not focal glutamate application alone, stops mitochondria, suggesting that an unidentified factor co-released with glutamate is required for mitochondrial arrest. A computational model of synaptic transmission-mediated mitochondrial arrest shows that the developmental increase in synapse number and transmission frequency can contribute substantially to the age-dependent decrease of mitochondrial motility.

Fragile X syndrome (FXS) is the most prevalent inherited cause of autism and is accompanied by behavioral and sensory deficits. Errors in the wiring of the brain during early development likely contribute to these deficits, but the underlying mechanisms are unclear. Spontaneous activity patterns, which are required for fine-tuning neuronal networks before the senses become active, are perturbed in rodent models of FXS. Here, we investigated spontaneous network activity patterns in the developing visual cortex of the Fmr1 knockout mouse using in vivo calcium imaging during the second postnatal week, before eye opening. We found that while the frequency, mean amplitude and duration of spontaneous network events were unchanged in the knockout mouse, pair-wise correlations between neurons were increased compared to wild type littermate controls. Further analysis revealed that interneuronal correlations were not generally increased, rather that low-synchronization events occurred relatively less frequently than high-synchronization events. Low-, but not high-, synchronization events have been associated with retinal inputs previously. Since we found that spontaneous retinal waves were normal in the knockout, our results suggest that peripherally driven activity is underrepresented in the Fmr1 KO visual cortex. Therefore, we propose that central gating of retinal inputs may be affected in FXS and that peripherally and centrally driven activity patterns are already unbalanced before eye opening in this disorder.

The structural and linguistic characteristics of companies’ annual reports (e.g., their length, complexity, and linguistic tone) and the qualitative information they contain (e.g., on the risks a company potentially faces) provide useful insights that can help increase the accuracy of predicting bankruptcy. In this study we use a sample of German companies that we compiled through propensity score matching to examine what type of textual information allows us to discriminate accurately between companies that are likely to go bankrupt and companies that, although financially distressed, are likely to remain solvent. Our findings provide empirical evidence that both the structural and linguistic characteristics of annual reports and the qualitative information they contain help discriminate between companies that are effectively bankrupt and companies that are solvent but financially distressed. Furthermore, this study provides empirical evidence that the “management obfuscation hypothesis” is valid because the tone of annual reports produced by bankrupt companies is quantifiably less negative than that of reports produced by companies that, although financially distressed, are likely to remain solvent.

Spontaneous activity drives the establishment of appropriate connectivity in different circuits during brain development. In the mouse primary visual cortex, two distinct patterns of spontaneous activity occur before vision onset: local low-synchronicity events originating in the retina and global high-synchronicity events originating in the cortex. We sought to determine the contribution of these activity patterns to jointly organize network connectivity through different activity-dependent plasticity rules. We postulated that local events shape cortical input selectivity and topography, while global events homeostatically regulate connection strength. However, to generate robust selectivity, we found that global events should adapt their amplitude to the history of preceding cortical activation. We confirmed this prediction by analyzing in vivo spontaneous cortical activity. The predicted adaptation leads to the sparsification of spontaneous activity on a slower timescale during development, demonstrating the remarkable capacity of the developing sensory cortex to acquire sensitivity to visual inputs after eye-opening.

The cure of a defaulted company has important implications for the estimation of the loss given default. In this study, we estimate the probability of a defaulted company being cured using data on a large international sample of defaulted companies. More specifically, we examine whether historic accounting information on a defaulted company and loan-related information are associated with that company's probability of being cured. The main finding of our analysis is that both accounting-based and loan-related independent variables increase the validity of cure prediction models.

Neurofibromatosis type 1 (NF1) is a common monogenic neurodevelopmental disorder associated with physical and cognitive problems. The cognitive issues are thought to arise from increased release of the neurotransmitter γ-amino butyric acid (GABA). Modulating the signaling pathways causing increased GABA release in a mouse model of NF1 reverts deficits in hippocampal learning. However, clinical trials based on these approaches have so far been unsuccessful. We therefore used a combination of slice electrophysiology, in vivo two-photon calcium imaging and optical imaging of intrinsic signal in a mouse model of NF1 to investigate whether cortical development is affected in NF1, possibly causing lifelong consequences that cannot be rescued by reducing inhibition later in life. We find that in NF1 mice of both sexes, inhibition increases strongly during the development of the visual cortex and remains high. While this increase in cortical inhibition does not affect spontaneous cortical activity patterns during early cortical development, the critical period for ocular dominance plasticity is shortened in NF1 mice due to its early closure but unaltered onset. Notably, after environmental enrichment, differences in inhibitory innervation and ocular dominance plasticity between NF1 mice and wild-type litter mates disappear. These results provide the first evidence for critical period dysregulation in NF1 and suggest that treatments aimed at normalizing levels of inhibition will need to start at early stages of development.Significance:Neurofibromatosis type 1 is associated with cognitive problems for which no treatment is currently available. This study shows that in a mouse model of Neurofibromatosis type 1, cortical inhibition is increased during development and critical period regulation is disturbed. Rearing the mice in an environment that stimulates cognitive function overcomes these deficits. These results uncover critical period dysregulation as a novel mechanism in the pathogenesis of Neurofibromatosis type 1. This suggests that targeting the affected signaling pathways in Neurofibromatosis type 1 for the treatment of cognitive disabilities may have to start at a much younger age than has so far been tested in clinical trials.

SummaryDuring early development, even before the senses are active, bursts of activity travel across the nervous system. This spontaneously generated activity drives the refinement of synaptic connections, preparing young networks for patterned sensory input. Synaptic fine-tuning relies not only on the presence of spontaneous activity, but also on the specific characteristics of these activity patterns, such as their frequency, amplitude and synchronicity. Here, we provide evidence that these crucial characteristics are shaped by the relative balance of excitation and inhibition, where patterns with distinct characteristics have different excitatory/inhibitory ratios. Inhibition can control whether cells participate during a spontaneous event, as pharmacogenetic suppression of the somatostatin (SST) expressing subtype of inhibitory interneurons increased cell recruitment and lateral spread of events.

© 2021 The Author(s)During early development, before the eyes open, synaptic refinement of sensory networks depends on activity generated by developing neurons themselves. In the mouse visual system, retinal cells spontaneously depolarize and recruit downstream neurons to bursts of activity, where the number of recruited cells determines the resolution of synaptic retinotopic refinement. Here we show that during the second post-natal week in mouse visual cortex, somatostatin (SST)-expressing interneurons control the recruitment of cells to retinally driven spontaneous activity. Suppressing SST interneurons increases cell participation and allows events to spread farther along the cortex. During the same developmental period, a second type of high-participation, retina-independent event occurs. During these events, cells receive such large excitatory charge that inhibition is overwhelmed and large parts of the cortex participate in each burst. These results reveal a role of SST interneurons in restricting retinally driven activity in the visual cortex, which may contribute to the refinement of retinotopy.

This study uses a generalized additive model to analyze nonlinear relationships and their effect on the bankruptcy prediction in terms of a company’s probability of default. Specifically, this study examines which of the performance indicators that are contained in a company’s annual financial statements affect nonlinearly that company’s probability of bankruptcy. Furthermore, this study examines the specific form that such nonlinear relationships take and interprets their economic relevance to predicting bankruptcy. On the basis of comprehensive data on German companies, this study shows empirically that there are statistically and economically relevant nonlinear relationships that influence the bankruptcy prediction. These nonlinear relationships are observed both below and above specific thresholds with respect to a company’s adjusted equity ratio, asset structure ratio based on tangible assets, adjusted return on assets, sales, and age. Our findings show that, to increase the accuracy of bankruptcy forecasts, it is necessary to take into account nonlinear relationships in models of bankruptcy prediction.

Zusammenfassung Zielsetzung Unternehmen des Gesundheitssektors unterscheiden sich in einer Vielzahl an leistungswirtschaftlichen sowie betriebswirtschaftlichen Merkmalen von anderen Wirtschaftsunternehmen. Der vorliegende Beitrag untersucht den Zusammenhang zwischen bilanziellen Strukturmerkmalen und dem Zahlungsausfall von Unternehmen des Gesundheitssektors. Methodik Die Analyse basiert auf Jahresabschlussdaten von deutschen Gesundheitsunternehmen der Jahre 2005 bis 2009 sowie zugehöriger Zahlungsausfalldaten. Unter Verwendung des Propensity Score Matching werden insgesamt 61 Zahlungsausfälle (18 Krankenhäuser sowie 43 sonstige Gesundheitsunternehmen) mit Hilfe der logistischen Regressionsanalyse statistisch ausgewertet. Ergebnisse Ein hoher Eigenkapitalanteil sowie ein großes Umlaufvermögen reduziert die Wahrscheinlichkeit des Zahlungsausfalls eines Unternehmens des Gesundheitssektors. Im Gegensatz zu anderen Wirtschaftsunternehmen hat die Rentabilität eines Unternehmens des Gesundheitssektors keinen empirisch nachweisbaren Einfluss auf die Wahrscheinlichkeit des Zahlungsausfalls. Schlussfolgerung Eine solide Finanzausstattung sowie eine zum großen Anteil auch kurzfristig liquidierbare Vermögensstruktur schützen die Unternehmen des Gesundheitssektors vor einem Zahlungsausfall. Die Rentabilität hat für die Unternehmensfortführung keine empirisch nachweisbare Aussagekraft. Dies resultiert möglicherweise aus der Regulierung des Gesundheitssektors in Bezug auf die medizinischen Leistungen sowie die damit einhergehenden Erlöse.

This study analyzes the renegotiations that take place between institutionalized public–private partnerships (PPPs) and their public clients drawing on survey data on the PPPs of the German Federal Armed Forces. Generally, both the party that initiates such renegotiations and the time at which renegotiations are launched determine the outcome of the PPP’s renegotiated remuneration. This effect is moderated by the degree of contract specificity and by a decrease in demand. Specifically, when the public client initiates the renegotiation of an incomplete contractual agreement due to a decrease in demand, it can successfully reduce the remuneration of the PPP.

Summary Spontaneous network activity shapes emerging neuronal circuits during early brain development prior to sensory perception. However, how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin differentially shapes spontaneous activity patterns across sensory cortices. In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in the primary visual cortex (V1), but it did not affect the frequency of spontaneous network events in the somatosensory cortex (S1). Patch-clamp recordings in slices and RNAscope showed that oxytocin affects S1 excitatory and inhibitory neurons similarly, whereas in V1, oxytocin targets only inhibitory neurons. Somatostatin-positive (SST+) interneurons expressed the oxytocin receptor and were activated by oxytocin in V1. Accordingly, pharmacogenetic silencing of V1 SST+ interneurons fully blocked oxytocin’s effect on inhibition in vitro as well its effect on spontaneous activity patterns in vivo. Thus, oxytocin decreases the excitatory/inhibitory (E/I) ratio by recruiting SST+ interneurons and modulates specific features of V1 spontaneous activity patterns that are crucial for the wiring and refining of developing sensory circuits., Graphical Abstract, Highlights • Oxytocin modulates spontaneous activity event patterns in the developing V1 • Oxytocin increases inhibition by activating somatostatin+ interneurons • SST+ neuron activity reduces event frequency and correlations, but not amplitude • In S1, oxytocin increases excitation and inhibition and does not modulate frequency, Maldonado et al. uncover oxytocin’s role in developing sensory cortices. In vivo, they show that oxytocin decreases the frequency and correlations of spontaneous activity patterns in V1 by specifically activating somatostatin+ interneurons. In S1, oxytocin increases both excitation and inhibition and does not affect spontaneous activity frequency.

The internal audit function (IAF) has become one of the main pillars of good corporate governance in recent years. Empirical findings show that the size of the IAF varies considerably across companies. This study analyzes the effect of selected company characteristics on the size of the IAF. First, a theoretical model outlines the idea that IAF size depends on company characteristics that affect existing information asymmetries within the company. Second, we test this relationship by analyzing comprehensive survey data obtained from chief audit executives from 283 Austrian, German, and Swiss organizations. Using a nonparametric regression approach, we identify a set of company characteristics as key drivers of IAF size. Furthermore, the empirical analysis identifies threshold levels for several metric company characteristics, such as the number of employees and the number of subsidiaries, whose effects on the size of the IAF change its intensity. Additionally, our study provides a helpful benchmark for the appropriateness of a company’s IAF size, which is of value for practitioners.

Zusammenfassung Zielsetzung Der Einsatz von Zielvereinbarungen als Grundlage der variablen Vergütung von Chefärzten wird durch die regulatorischen Bestimmungen des § 135c SGB V n. F. sowie berufsrechtliche Vorgaben erheblich eingeschränkt. Der vorliegende Beitrag analysiert die Auswirkungen auf die Zweckmäßigkeit sowie den zukünftigen Einsatz von Zielvereinbarungen im Krankenhaus. Methodik Die Analyse basiert auf einer empirischen Auswertung der von der Koordinierungsstelle „Zielvereinbarungen in Chefarztverträgen“ bewerteten Zulässigkeit von Zielvereinbarungen sowie auf einer konzeptionellen Auseinandersetzung mit den Problembereichen der zulässigen Zielvereinbarungen aus der Perspektive des Krankenhauses. Ergebnisse Während leistungsbezogene Zielvereinbarungen von der Koordinierungsstelle „Zielvereinbarungen in Chefarztverträgen“ als nicht akzeptabel angesehen werden, sind andersartige Zielvereinbarungen aus der Perspektive des Krankenhauses ebenfalls als problembehaftet einzustufen. Schlussfolgerung Aufgrund der regulatorischen Vorgaben sind die möglichen Zielvereinbarungen als zu einseitig zu beurteilen, da sie die Ziele des Krankenhauses nicht in ihrer Gesamtheit wiedergeben. Unter Beachtung der regulatorischen Vorgaben erscheint die Nutzung von Zielvorgaben als Personalführungsinstrument als nicht zweckmäßig.

Our study charts the development of the accounting community by tracing publication trends and changes in methodology, including a major shift towards positive and neoclassical economics, multi-authorship and the prevalence of particular institutions, as reflected in The Accounting Review (TAR) between 1926 and 2014. Using network analysis, we identify distinct networks in this community and show that while the network of the institutions to which TAR authors were affiliated in the analysed period became diverse, the network of the institutions from which TAR authors received their doctorate remained dominated by a relatively small group of elite US universities.

Option-like situations in non-financial markets, often referred to as real options, are usually discussed and analyzed in the context of investment decisions. In spite of the real options literature’s focus on investment decisions, option-like situations are also frequently encountered in operating decisions. For instance, decisions on the operating mode of a flexible machine in the presence of switching costs can be characterized as complex real options problems with multiple compound options. For an optimal long-term solution, short-term decision rules must consider the value of these options. In this paper we first show how a fully rational decision rule that takes the long-term consequences of short-term decisions into account can be derived within the real options framework. We contrast the outcomes of decisions according to this benchmark rule with the outcomes of decisions according to the traditional decision rule based on current contribution margin and illustrate our findings with a simulation analysis providing for a rich set of environments characterized by different levels of uncertainty and different switching costs. A major drawback of the options-based rule is the necessity to estimate option values at every decision point drawing on information from all future periods. We therefore analyze how a simplified options-based decision rule that looks ahead only one period performs against the benchmark rule. In an extension of the simulation analysis we find that the simplified decision rule serves as a good heuristic and improves decision-making similar to the benchmark rule while at the same time being much more likely to be implemented in practice.

This study uses data on consumer credit provided by a German retail and trading company along with generalized additive models to analyze nonlinear relationships and their effect on predicting the probability of default in the context of consumer credit scoring. In particular, this study examines which aspects of the contract and which characteristics of the debtor are nonlinearly related to the probability that specific debtors will default on the loans they are seeking to obtain. The findings of our analysis provide clear empirical evidence that certain contract and debtor characteristics have nonlinear and nonmonotonic effects on the probability that a specific debtor will default on their consumer credit. The results of our analysis and the forms that these nonlinear relationships take are interpreted with regard to their economic relevance. Specifically, the study shows that the nonlinear relationships identified are economically relevant because they take into account the costs of a range of misclassification errors. On the basis of this evidence, the study recommends that analysts include nonlinear relationships in the models they design to predict consumer default, although including such relationships increases the complexity of the models that are applied for this purpose.

SummarySpontaneous activity fine-tunes neuronal connections in the developing brain. To explore the underlying synaptic plasticity mechanisms, we monitored naturally occurring changes in spontaneous activity at individual synapses with whole-cell patch-clamp recordings and simultaneous calcium imaging in the mouse visual cortex in vivo. Analyzing activity changes across large populations of synapses revealed a simple and efficient local plasticity rule: synapses that exhibit low synchronicity with nearby neighbors (

In a setting where the owner of a company delegates the authority to make overlapping capacity investments to a manager, the decision on such investments depends on how the decision-maker perceives the marginal cost of capacity. This covers the cost for one additional unit of capacity made available for only one period of time, although expenditures for capacity investments are a common cost of capacity that can be used over multiple periods. If the manager’s performance measure is residual income, the level of the marginal cost of capacity and the associated investment incentives depend on the applied depreciation schedule and the manager’s time preferences. We examine the direction of the effect of several depreciation schedules on the marginal cost of capacity that the manager perceives and analyze the extent to which this cost is distorted. Our analysis shows that a performance measure based on residual income, combined with several practically relevant depreciation schedules, creates the desired investment incentives for the manager, because differently structured depreciation schedules have a relatively small effect on the level of the marginal cost of capacity. We also examine how partial direct expensing can increase the objective congruence of residual income as a managerial performance measure if the straight-line depreciation schedule or the annuity depreciation schedule is used.

During development, activity-dependent synaptic plasticity refines neuronal networks with high precision. For example, spontaneous activity helps sorting synaptic inputs with similar activity patterns into clusters to enhance neuronal computations in the mature brain. Here, we show that TrkB activation and postsynaptic brain-derived neurotrophic factor (BDNF) are required for synaptic clustering in developing hippocampal neurons. Moreover, BDNF and TrkB modulate transmission at synapses depending on their clustering state, indicating that endogenous BDNF/TrkB signaling stabilizes locally synchronized synapses. Together with our previous data on proBDNF/p75NTR signaling, these findings suggest a push-pull plasticity mechanism for synaptic clustering: BDNF stabilizes clustered synapses while proBDNF downregulates out-of-sync synapses. This idea is supported by our observation that synaptic clustering requires matrix-metalloproteinase-9 activity, a proBDNF-to-BDNF converting enzyme. Finally, NMDA receptor activation mediates out-of-sync depression upstream of proBDNF signaling. Together, these data delineate an efficient plasticity mechanism where proBDNF and mature BDNF establish synaptic clustering through antagonistic modulation of synaptic transmission. Niculescu et al. found that synaptic clustering requires BDNF/TrkB signaling, activity of the proBDNF-to-BDNF conversion enzyme MMP9, and NMDA receptor activation. Their study delineates a push-pull plasticity mechanism where BDNF stabilizes clustered synapses while its precursor, proBDNF, depresses unclustered synapses, together ensuring robust clustering of synaptic inputs in developing neurons.

The presence of direct, cytoplasmatic, communication between neurons in the brain of vertebrates has been demonstrated a long time ago. These gap junctions have been characterized in many brain areas in terms of subunit composition, biophysical properties, neuronal connectivity patterns, and developmental regulation. Although interesting findings emerged, showing that different subunits are specifically regulated during development, or that excitatory and inhibitory neuronal networks exhibit various electrical connectivity patterns, gap junctions did not receive much further interest. Originally, it was believed that gap junctions represent simple passageways for electrical and biochemical coordination early in development. Today, we know that gap junction connectivity is tightly regulated, following independent developmental patterns for excitatory and inhibitory networks. Electrical connections are important for many specific functions of neurons, and are, for example, required for the development of neuronal stimulus tuning in the visual system. Here, we integrate the available data on neuronal connectivity and gap junction properties, as well as the most recent findings concerning the functional implications of electrical connections in the developing thalamus and neocortex.

Corporate Governance hat in der betriebswirtschaftlichen Forschung in den letzten beiden Dekaden kontinuierlich an Bedeutung gewonnen. Ungeachtet dessen wird die Corporate Governance-Forschung nach wie vor als weitestgehend unsystematischer, in viele Einzelthemen zerfallener Strang der betriebswirtschaftlichen Literatur wahrgenommen. Der vorliegende Beitrag analysiert empirisch die Entwicklung der betriebswirtschaftlichen Corporate Governance-Forschung im deutschsprachigen Raum. Als Datenbasis fur eine Zitations-, Kozitations- und Clusteranalyse dienen 267 Corporate Governance-Beitrage mit mehr als 10.000 Zitationen. Die erhobenen Daten werden in sechs Cluster zur Darstellung der thematischen Schwerpunkte der betriebswirtschaftlichen Corporate Governance-Forschung unterteilt und als Kozitationsnetzwerk visuell dargestellt. Zudem wird die historische Entwicklung der betriebswirtschaftlichen Corporate Governance-Forschung herausgearbeitet, indem die 267 herangezogenen Corporate Governance-Beitrage den sechs Clustern unter Berucksichtigung des Publikationszeitpunktes zugeordnet werden.

Both the Groves scheme and profit-sharing can lead to truthful reports produced by the better informed divisional manager for the benefit of the less well informed headquarters in charge of intra-firm resource allocation. However, both schemes have certain shortcomings: while the Groves scheme is susceptible to collusion among divisional managers, profit-sharing does not strictly ensure that truthful reporting is the dominant strategy in the case of each divisional manager. Both shortcomings can be remedied by combining the Groves scheme with an additional penalty scheme related to the Weitzman scheme. Using a game-theoretic approach, this paper introduces a new success indicator that establishes truthful reporting as the dominant strategy and prevents collusion or contractual agreements among divisional managers. In sum, this paper’s theoretical results predict that applying the new success indicator leads to a higher level of truthful reporting, and therefore to more efficient resource allocation, than applying either the Groves scheme or profit-sharing alone.

The brain is programmed to drive behaviour by precisely wiring the appropriate neuronal circuits. Wiring and rewiring of neuronal circuits largely depends on the orchestrated changes in the strengths of synaptic contacts. Here, we review how the rules of synaptic plasticity change during development of the brain, from birth to independence. We focus on the changes that occur at the postsynaptic side of excitatory glutamatergic synapses in the rodent hippocampus and neocortex. First we summarize the current data on the structure of synapses and the developmental expression patterns of the key molecular players of synaptic plasticity, N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as pivotal kinases (Ca(2+)/calmodulin-dependent protein kinase II, protein kinase A, protein kinase C) and phosphatases (PP1, PP2A, PP2B). In the second part we relate these findings to important characteristics of the emerging network. We argue that the concerted and gradual shifts in the usage of plasticity molecules comply with the changing need for (re)wiring neuronal circuits.

Calcium imaging has become a widely used technique to probe neuronal activity on the cellular and subcellular levels. In contrast to standard electrophysiological methods, calcium imaging resolves sub- and suprathreshold activation patterns in structures as small as fine dendritic branches and spines. This review highlights recent findings gained on the subcellular level using calcium imaging, with special emphasis on synaptic transmission and plasticity in individual spines. Since imaging allows monitoring activity across populations of synapses, it has recently been adopted to investigate how dendrites integrate information from many synapses. Future experiments, ideally carried out in vivo, will reveal how the dendritic tree integrates and computes afferent signals. For example, it is now possible to directly test the concept that dendritic inputs are clustered and that single dendrites or dendritic stretches act as independent computational units.

Studying changing synaptic activity patterns during development provides a wealth of information on how activity-dependent processes shape synaptic connectivity. In this chapter we introduce a method that combines whole-cell electrophysiology with calcium imaging to map functional synaptic sites on the dendritic tree and follow their activity over time. The key strength of this method lies in its ability to distinguish between synaptic and non-synaptic calcium signaling by their coincidence with synaptic currents measured at the soma. Next to the required materials and protocols that are necessary to perform these experiments, we thoroughly discuss how the acquired data can be analyzed. Since this method can be employed in many neuronal systems we believe that it can be a valuable tool to study developmental changes in synaptic connectivity.

Studying changing synaptic activity patterns during development provides a wealth of information on how activity-dependent processes shape synaptic connectivity. In this chapter we introduce a method that combines whole-cell electrophysiology with calcium imaging to map functional synaptic sites on the dendritic tree and follow their activity over time. The key strength of this method lies in its ability to distinguish between synaptic and non-synaptic calcium signaling by their coincidence with synaptic currents measured at the soma. Next to the required materials and protocols that are necessary to perform these experiments, we thoroughly discuss how the acquired data can be analyzed. Since this method can be employed in many neuronal systems we believe that it can be a valuable tool to study developmental changes in synaptic connectivity.

In order to accurately process incoming sensory stimuli, neurons must be organized into functional networks, with both genetic and environmental factors influencing the precise arrangement of connections between cells. Teasing apart the relative contributions of molecular guidance cues, spontaneous activity and visual experience during this maturation is on-going. During development of the sensory system, the first, rough organization of connections is created by molecular factors. These connections are then modulated by the intrinsically generated activity of neurons, even before the senses have become operational. Spontaneous waves of depolarisations sweep across the nervous system, placing them in a prime position to strengthen correct connections and weaken others, shaping synapses into a useful network. A large body of work now supports the idea that, rather than being a mere side-effect of the system, spontaneous activity actually contains information which readies the nervous system so that, as soon as the senses become active, sensory information can be utilized by the animal. An example is the neonatal mouse. As soon as the eyelids first open, neurons in the cortex respond to visual information without the animal having previously encountered structured sensory input (Cang et al., 2005a; Ko et al., 2013; Rochefort et al., 2011; Zhang et al., 2012). In vivo imaging techniques have advanced considerably, allowing observation of the natural activity in the brain of living animals down to the level of the individual synapse. New (opto)genetic methods make it possible to subtly modulate the spatio-temporal properties of activity, aiding our understanding of how these characteristics relate to the function of spontaneous activity. Such experiments have had a huge impact on our knowledge by permitting direct testing of ideas about the plasticity mechanisms at play in the intact system, opening up a provocative range of fresh questions. Here, we intend to outline the most recent descriptions of spontaneous activity patterns in rodent developing sensory areas, as well as the inferences we can make about the information content of those activity patterns and ideas about the plasticity rules that allow this activity to shape the young brain.

In order to accurately process incoming sensory stimuli, neurons must be organized into functional networks, with both genetic and environmental factors influencing the precise arrangement of connections between cells. Teasing apart the relative contributions of molecular guidance cues, spontaneous activity and visual experience during this maturation is on-going. During development of the sensory system, the first, rough organization of connections is created by molecular factors. These connections are then modulated by the intrinsically generated activity of neurons, even before the senses have become operational. Spontaneous waves of depolarisations sweep across the nervous system, placing them in a prime position to strengthen correct connections and weaken others, shaping synapses into a useful network. A large body of work now supports the idea that, rather than being a mere side-effect of the system, spontaneous activity actually contains information which readies the nervous system so that, as soon as the senses become active, sensory information can be utilized by the animal. An example is the neonatal mouse. As soon as the eyelids first open, neurons in the cortex respond to visual information without the animal having previously encountered structured sensory input (Cang et al., 2005a; Ko et al., 2013; Rochefort et al., 2011; Zhang et al., 2012). In vivo imaging techniques have advanced considerably, allowing observation of the natural activity in the brain of living animals down to the level of the individual synapse. New (opto)genetic methods make it possible to subtly modulate the spatio-temporal properties of activity, aiding our understanding of how these characteristics relate to the function of spontaneous activity. Such experiments have had a huge impact on our knowledge by permitting direct testing of ideas about the plasticity mechanisms at play in the intact system, opening up a provocative range of fresh questions. Here, we intend to outline the most recent descriptions of spontaneous activity patterns in rodent developing sensory areas, as well as the inferences we can make about the information content of those activity patterns and ideas about the plasticity rules that allow this activity to shape the young brain.

Summary Mitochondria buffer intracellular Ca 2+ and provide energy [1]. Because synaptic structures with high Ca 2+ buffering [2–4] or energy demand [5] are often localized far away from the soma, mitochondria are actively transported to these sites [6–11]. Also, the removal and degradation of mitochondria are tightly regulated [9, 12, 13], because dysfunctional mitochondria are a source of reactive oxygen species, which can damage the cell [14]. Deficits in mitochondrial trafficking have been proposed to contribute to the pathogenesis of Parkinson's disease, schizophrenia, amyotrophic lateral sclerosis, optic atrophy, and Alzheimer's disease [13, 15–19]. In neuronal cultures, about a third of mitochondria are motile, whereas the majority remains stationary for several days [8, 20]. Activity-dependent mechanisms cause mitochondria to stop at synaptic sites [7, 8, 20, 21], which affects synapse function and maintenance. Reducing mitochondrial content in dendrites decreases spine density [22, 23], whereas increasing mitochondrial content or activity increases it [7]. These bidirectional interactions between synaptic activity and mitochondrial trafficking suggest that mitochondria may regulate synaptic plasticity. Here we investigated the dynamics of mitochondria in relation to axonal boutons of neocortical pyramidal neurons for the first time in vivo. We find that under these circumstances practically all mitochondria are stationary, both during development and in adulthood. In adult visual cortex, mitochondria are preferentially localized at putative boutons, where they remain for several days. Retinal-lesion-induced cortical plasticity increases turnover of putative boutons but leaves mitochondrial turnover unaffected. We conclude that in visual cortex in vivo, mitochondria are less dynamic than in vitro, and that structural plasticity does not affect mitochondrial dynamics.