We propose that sleep is linked to synaptic homeostasis. Specifically, we propose that: (1) Wakefulness is associated with synaptic potentiation in cortical circuits; (2) synaptic potentiation is tied to the homeostatic regulation of slow wave activity; (3) slow wave activity is associated with synaptic downscaling; and (4) synaptic downscaling is tied to several beneficial effects of sleep, including performance enhancement.

Complex functions of the central nervous system such as learning and memory are believed to result from the modulation of the synaptic transmission between neurons. The sequence of events leading to the fusion of synaptic vesicles at the presynaptic active zone and the detection of this signal at the postsynaptic density involve the activity of ion channels and neurotransmitter receptors. Their accumulation and dynamic exchange at synapses are dependent on their interaction with synaptic scaffolds. These are (...) class='Hi'>synaptic structures composed of adaptor proteins that provide binding sites for receptors and channels as well as other synaptic proteins. While in its entirety the synaptic scaffold is a relatively stable structure, individual adaptor proteins exchange at a fast time scale. These properties of scaffolds help to ensure the stability of synaptic transmission while permitting the modulation of synaptic strength. Here, we review the dynamics of the synaptic scaffold and of adaptor proteins in relation to their roles in the organisation of the synapse as well as in the clustering and trafficking of receptor proteins. BioEssays 30:1062–1074, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Our model integrates the nativist assumption of prespecified neural structures underpinning basic emotions with the constructionist view that emotions are assembled from psychological constituents. From a dynamic systems perspective, the nervous system self-organizes in different ways at different time scales, in relation to functions served by emotions. At the evolutionary scale, brain parts and their connections are specified by selective pressures. At the scale of development, connectivity is revised through synaptic shaping. At the scale of real time, temporary networks (...) of synchronized activity mediate responses to situations. To the degree that humans share common emotional functions, neural structuration is similar across scales, giving rise to “basic” emotions. However, unique developmental and situational factors select for neural configurations mediating emotional variants. (shrink)

A general conceptual framework for large-scale neocortical dynamics based on data from many laboratories is applied to a variety of experimental designs, spatial scales, and brain states. Partly distinct, but interacting local processes (e.g., neural networks) arise from functional segregation. Global processes arise from functional integration and can facilitate (top down) synchronous activity in remote cell groups that function simultaneously at several different spatial scales. Simultaneous local processes may help drive (bottom up) macroscopic global dynamics observed with electroencephalography (EEG) or (...) magnetoencephalography (MEG). A local/global dynamic theory that is consistent with EEG data and the proposed conceptual framework is outlined. This theory is neutral about properties of neural networks embedded in macroscopic fields, but its global component makes several qualitative and semiquantitative predictions about EEG measures of traveling and standing wave phenomena. A more general “metatheory” suggests what large-scale quantitative theories of neocortical dynamics may be like when more accurate treatment of local and nonlinear effects is achieved. The theory describes the dynamics of excitatory and inhibitory synaptic action fields. EEG and MEG provide large-scale estimates of modulation of these synaptic fields around background levels. Brain states are determined by neuromodulatory control parameters. Purely local states are dominated by local feedback gains and rise and decay times of postsynaptic potentials. Dominant local frequencies vary with brain region. Other states are purely global, with moderate to high coherence over large distances. Multiple global mode frequencies arise from a combination of delays in corticocortical axons and neocortical boundary conditions. Global frequencies are identical in all cortical regions, but most states involve dynamic interactions between local networks and the global system. EEG frequencies may involve a “matching” of local resonant frequencies with one or more of the many, closely spaced global frequencies. Key Words: binding problem; cell assemblies; coherence; EEG; limit cycles; neocortical dynamics; pacemakers; phase locking; spatial scale; standing waves; synchronization. Footnotes1 The relationship between the synaptic action fields proposed in the target article and cell assemblies is clarified with Figure R1 (p. 416) of the Response. (This figure was not available to Commentators. (shrink)

There is some complementarity of models for the origin of the electroencephalogram (EEG) and neural network models for information storage in brainlike systems. From the EEG models of Freeman, of Nunez, and of the authors' group we argue that the wavelike processes revealed in the EEG exhibit linear and near-equilibrium dynamics at macroscopic scale, despite extremely nonlinear – probably chaotic – dynamics at microscopic scale. Simulations of cortical neuronal interactions at global and microscopic scales are then presented. The simulations depend (...) on anatomical and physiological estimates of synaptic densities, coupling symmetries, synaptic gain, dendritic time constants, and axonal delays. It is shown that the frequency content, wave velocities, frequency/wavenumber spectra and response to cortical activation of the electrocorticogram (ECoG) can be reproduced by a “lumped” simulation treating small cortical areas as single-function units. The corresponding cellular neural network simulation has properties that include those of attractor neural networks proposed by Amit and by Parisi. Within the simulations at both scales, sharp transitions occur between low and high cell firing rates. These transitions may form a basis for neural interactions across scale. To maintain overall cortical dynamics in the normal low firing-rate range, interactions between the cortex and the subcortical systems are required to prevent runaway global excitation. Thus, the interaction of cortex and subcortex via corticostriatal and related pathways may partly regulate global dynamics by a principle analogous to adiabatic control of artificial neural networks. (shrink)

Our families are our first and most important ethical training grounds. But what is the family? And what are our ethical commitments to our family members and to the broader moral community? After a brief introductory chapter on basic ethical concepts and theories, the essays in this volume provide readers with ethical analyses of issues ranging from same-sex marriage to a controversial proposal to "license" parents. The chapters cover love, sex, marriage, parents and children, the relationship between the family and (...) the larger moral community, and the influence of emerging technologies on the ethical issues inherent in family life. The volume is intended to open up this exciting territory in applied ethics to those interested in philosophy, family studies, social work, and to anyone who wants a deeper understanding of the ethical forces at work in this most basic social institution. (shrink)

Irecently admitted a 93-year-old Spanish-speaking woman with bilateral flank pain. A thorough history revealed her pain was due to constipation and intense straining with each bowel movement, but a language barrier, a mild troponin elevation, and "new atrial fibrillation" on her EKG triggered the Emergency Department physician to admit her for observation. When I went to see her, she mentioned her pain was worse since she was told we would need to monitor her heart overnight. She asked, "Is everything ok (...) with my heart?"To assess that question, I prepared to perform a bedside ultrasound, also known as point-of-care ultrasound. We moved from a hallway in the ED to a room for more privacy, and the patient... (shrink)

Critical discussion of Quine's concepts of purely referential occurrence/position. It is argued from the perspective of a Russellian view of truth that existential generalization and substitutivity of identity are non-equivalent tests for referential occurrence/position, and that the former rather than the latter is the appropriate test.

Critical discussion of Quine's concepts of purely referential occurrence/position. It is argued from the perspective of a Russellian view of truth that existential generalization and substitutivity of identity are non-equivalent tests for referential occurrence/position, and that the former rather than the latter is the appropriate test.

Human–Human and Human–Robot Interaction are known to be influenced by a variety of modalities and parameters. Nevertheless, it remains a challenge to anticipate how a given mobile robot’s navigation and appearance will impact how it is perceived by humans. Drawing a parallel with vocal prosody, we introduce the notion of movement prosody, which encompasses spatio-temporal and appearance dimensions which are involved in a person’s perceptual experience of interacting with a mobile robot. We design a novel robot motion corpus, encompassing variables (...) related to the kinematics, gaze, and appearance of the robot, which we hypothesize are involved in movement prosody. Initial results of three perception experiments suggest that these variables have significant influences on participants’ perceptions of robot socio-affects and physical attributes. (shrink)

Written in an engaging narrative style these philosophical investigations undermine racist hierarchies along with false natualistic conceptions of the meanings of race and universalistic understandings of gender, by considering whiteness as it shapes and is infused by gender, class, sexuality, and culture. Central to this project are questions about how it is that culture and the state create such a wide range of different people who understand themselves as white. The essays collected here discuss how one learns to be a (...) good white Southern woman, what it means to pass as white, and whether there really is a dilemma that accompanies white privilege. (shrink)

We implemented a user-centered approach to the design of an artificial intelligence (AI) system that provides users with access to information about the workings of the United States federal court system regardless of their technical background. Presently, most of the records associated with the federal judiciary are provided through a federal system that does not support exploration aimed at discovering systematic patterns about court activities. In addition, many users lack the data analytical skills necessary to conduct their own analyses and (...) convert data into information. We conducted interviews, observations, and surveys to uncover the needs of our users and discuss the development of an intuitive platform informed from these needs that makes it possible for legal scholars, lawyers, and journalists to discover answers to more advanced questions about the federal court system. We report on results from usability testing and discuss design implications for AI and law practitioners and researchers. (shrink)

Intensive care physicians often must rely on substitute decision makers to address all dimensions of the construct of.

The COVID-19 global health emergency has greatly impacted the educational field. Faced with unprecedented stress situations, professors, students, and families have employed various coping and resilience strategies throughout the confinement period. High and persistent stress levels are associated with other pathologies; hence, their detection and prevention are needed. Consequently, this study aimed to design a predictive model of stress in the educational field based on artificial intelligence that included certain sociodemographic variables, coping strategies, and resilience capacity, and to study the (...) relationship between them. The non-probabilistic snowball sampling method was used, involving 337 people from the university education community in south-eastern Spain. The Perceived Stress Scale, Stress Management Questionnaire, and Brief Resilience Scale were administered. The Statistical Package for the Social Sciences was used to design the architecture of artificial neural networks. The results found that stress levels could be predicted by the synaptic weights of coping strategies and timing of the epidemic, with a predictive capacity of over 80% found in the neural network model. Additionally, direct and significant associations were identified between the use of certain coping strategies, stress levels, and resilience. The conclusions of this research are essential for effective stress detection, and therefore, early intervention in the field of educational psychology, by discussing the influence of resilience or lack thereof on the prediction of stress levels. Identifying the variables that maintain a greater predictive power in stress levels is an effective strategy to design more adjusted prevention programs and to anticipate the needs of the community. (shrink)

Sleep strengthens memories by repeatedly reactivating associated neuron ensembles. Our studies show that although long-term memory for a medium number of word-pairs benefits from sleep, a large number does not. This suggests an upper limit to the amount of information that has access to sleep-dependent declarative memory consolidation, which is possibly linked to the availability of reactivation opportunities. Due to competing processes of global forgetting that are active during sleep, we hypothesized that even larger amounts of information would enhance the (...) proportion of information that is actively forgotten during sleep. In the present study, we aimed to induce such forgetting by challenging the sleeping brain with vast amounts of to be remembered information. For this, 78 participants learned a very large number of 640 word-pairs interspersed with periods of quiet awake rest over the course of an entire day and then either slept or stayed awake during the night. Recall was tested after another night of regular sleep. Results revealed comparable retention rates between the sleep and wake groups. Although this null-effect can be reconciled with the concept of limited capacities available for sleep-dependent consolidation, it contradicts our hypothesis that sleep would increase forgetting compared to the wake group. Additional exploratory analyses relying on equivalence testing and Bayesian statistics reveal that there is evidence against sleep having a detrimental effect on the retention of declarative memory at high information loads. We argue that forgetting occurs in both wake and sleep states through different mechanisms, i.e., through increased interference and through global synaptic downscaling, respectively. Both of these processes might scale similarly with information load. (shrink)

Many kinds of complex systems exhibit characteristic patterns of temporal correlations that emerge as the result of functional interactions within a structured network. One such complex system is the brain, composed of numerous neuronal units linked by synaptic connections. The activity of these neuronal units gives rise to dynamic states that are characterized by specific patterns of neuronal activation and co-activation. These patterns, called functional connectivity, are possible neural correlates of perceptual and cognitive processes. Which functional connectivity patterns arise (...) depends on the anatomical structure of the underlying network, which in turn is modified by a broad range of activity-dependent processes. Given this intricate relationship between structure and function, the question of how patterns of anatomical connectivity constrain or determine dynamical patterns is of considerable theoretical importance. The present study develops computational tools to analyze networks in terms of their structure and dynamics. We identify different classes of network, including networks that are characterized by high complexity. These highly complex networks have distinct structural characteristics such as clustered connectivity and short wiring length similar to those of large-scale networks of the cerebral cortex. (shrink)

Traditionally, the impairment of cognitive functions in Alzheimeŕs disease (AD) is thought to result from a reduction in neuronal and synaptic activities, and ultimately cell death. Here, we review recent in vivo evidence from mouse models and human patients indicating that, particularly in early stages of AD, neuronal circuits are hyperactive instead of hypoactive. Functional analyses at many levels, from single neurons to neuronal populations to large‐scale networks, with a variety of electrophysiological and imaging techniques have revealed two forms (...) of AD‐related hyperactivity and provided first insights into the synaptic mechanisms. The unexpected finding that hyperactivity is an early neuronal dysfunction represents a major conceptual shift in our understanding of AD that may have important implications for the development of therapeutic approaches. (shrink)

Invertebrate genetic models with their tractable neuromuscular systems are effective vehicles for the study of human nerve and muscle disorders. This is exemplified by insights made into spinal muscular atrophy (SMA) using the fruit fly Drosophila melanogaster and the nematode worm Caenorhabditis elegans. For speed and economy, these invertebrates offer convenient, whole‐organism platforms for genetic screening as well as RNA interference (RNAi) and chemical library screens, permitting the rapid testing of hypotheses related to disease mechanisms and the exploration of new (...) therapeutic routes and drug candidates. Here, we discuss recent developments encompassing synaptic physiology, RNA processing, and screening of compound and genome‐scale RNAi libraries, showcasing the importance of invertebrate SMA models.Editor's suggested further reading in BioEssays: SMN and Gemins: ‘We are family’... or are we? Abstract. (shrink)

Human brains exhibit complex dynamic behaviour measured by external recordings of electric (EEG) and magnetic fields (MEG). These data reveal synaptic field oscillations in neocortex at millisecond temporal and centimetre spatial scales. We suggest that the neural networks underlying behaviour and cognition may be viewed as embedded in these synaptic action fields, analogous to social networks embedded in a culture. These synaptic fields may facilitate the binding of disparate networks to produce a behaviour and consciousness that appears (...) unified to external observers. EEG, MEG, anatomy, physiology, and complex physical systems are considered here to suggest fundamental physical and biological properties of human brains that may be required for human consciousness to occur. We do not claim that these tissue properties are necessarily causal; however, they appear to be strongly correlated with human consciousness. Emphasis is placed on the hierarchical structure of brains, non-local connections between distant cortical regions, and resonant interactions between networks. While several of these ideas are supported by both experimental data and mathematical theory, the mathematics is replaced by metaphor for this paper. One conjecture is that the schizophrenias and other diseases occur when neural networks fail to conform to global synaptic fields. Perhaps consciousness is a resonance phenomenon and only properly tuned brains can orchestrate the beautiful music of sentience. (shrink)

Bidirectional trans‐synaptic signaling is essential for the formation, maturation, and plasticity of synaptic connections. Synaptic cell adhesion molecules (CAMs) are prime drivers in shaping the identities of trans‐synaptic signaling pathways. A series of recent studies provide evidence that diverse presynaptic cell adhesion proteins dictate the regulation of specific synaptic properties in postsynaptic neurons. Focusing on mammalian synaptic CAMs, this article outlines several exemplary cases supporting this notion and highlights how these trans‐synaptic signaling pathways (...) collectively contribute to the specificity and diversity of neural circuit architecture. (shrink)

Long‐term potentiation (LTP) of excitatory synapses is a leading model to explain the concept of information storage in the brain. Multiple mechanisms contribute to LTP, but central amongst them is an increased sensitivity of the postsynaptic membrane to neurotransmitter release. This sensitivity is predominantly determined by the abundance and localization of AMPA‐type glutamate receptors (AMPARs). A combination of AMPAR structural data, super‐resolution imaging of excitatory synapses, and an abundance of electrophysiological studies are providing an ever‐clearer picture of how AMPARs are (...) recruited and organized at synaptic junctions. Here, we review the latest insights into this process, and discuss how both cytoplasmic and extracellular receptor elements cooperate to tune the AMPAR response at the hippocampal CA1 synapse. (shrink)

The neuromuscular junction has been used for several decades as an excellent model system to examine the cellular and molecular events involved in the formation and maintenance of a differentiated chemical synapse. In this context, several laboratories have focused their efforts over the last 15 years on the important contribution of transcriptional mechanisms to the regulation of the development and plasticity of the postsynaptic apparatus in muscle fibers. Converging lines of evidence now indicate that post‐transcriptional events, operating at the level (...) of mRNA stability and targeting, are likely to also play key roles at the neuromuscular junction. Here, we present the recent findings highlighting the role of these additional molecular events and extend our review to include data showing that post‐transcriptional events are also important in the control of the expression of genes encoding synaptic proteins in muscle cells placed under different conditions. Finally, we discuss the possibility that mis‐regulation of post‐transcriptional events can occur in certain neuromuscular diseases and cause abnormalities of the neuromuscular junction. BioEssays 25:25–31, 2003. © 2002 Wiley Periodicals, Inc. (shrink)