In the development of the immune response, the dendritic cell subset of leukocytes plays a key role in enhancing immunogenicity. Dendritic cells can pick up antigens in the tissues and move to lymphoid organs, through which T cells continually recirculate. It is proposed that dendritic cells at these sites express functions which have beenidentified in tissue culture models. These involve efficient binding to antigen‐specific T lymphocytes, as well as the induction of the lymphokines and growth factor (...) receptors required for immunity. The dendritic cell system, apparently under the control of cytokines, is a sentinel designed to signal T cells that a significant antigen burden is present, and to generate the activated T lymphoblasts that interact with many other cell types to bring about an immune response. (shrink)

The Cell Ontology (CL) is designed to provide a standardized representation of cell types for data annotation. Currently, the CL employs multiple is_a relations, defining cell types in terms of histological, functional, and lineage properties, and the majority of definitions are written with sufficient generality to hold across multiple species. This approach limits the CL’s utility for cross-species data integration. To address this problem, we developed a method for the ontological representation of cells and applied this method (...) to develop a dendritic cell ontology (DC-CL). DC-CL subtypes are delineated on the basis of surface protein expression, systematically including both species-general and species-specific types and optimizing DC-CL for the analysis of flow cytometry data. This approach brings benefits in the form of increased accuracy, support for reasoning, and interoperability with other ontology resources. 104. Barry Smith, “Toward a Realistic Science of Environments”, Ecological Psychology, 2009, 21 (2), April-June, 121-130. Abstract: The perceptual psychologist J. J. Gibson embraces a radically externalistic view of mind and action. We have, for Gibson, not a Cartesian mind or soul, with its interior theater of contents and the consequent problem of explaining how this mind or soul and its psychological environment can succeed in grasping physical objects external to itself. Rather, we have a perceiving, acting organism, whose perceptions and actions are always already tuned to the parts and moments, the things and surfaces, of its external environment. We describe how on this basis Gibson sought to develop a realist science of environments which will be ‘consistent with physics, mechanics, optics, acoustics, and chemistry’. (shrink)

The idea that the thalamo-cortical system is the crucial constituent of the neurobiological mechanisms of consciousness has a long history. For the last few decades, however, consciousness research has to a large extent overlooked the interplay between the cortex and thalamus. Here we revive an integrated view of the neurobiology of consciousness by presenting and discussing several recent major findings about the role of the thalamocortical interactions in consciousness. Based on these findings we propose a specific cellular mechanism how thalamic (...) nuclei modulate the integration of different processing streams within single cortical pyramidal neurons. This theory is inspired by recent work done in rodents, but it integrates decades of work conducted on various species. We illustrate how this new view readily explains various properties and experimental phenomena associated with conscious experience. We discuss the implications of this idea and some of the experiments that need to be done in order to test it. Our view bridges two long-standing perspectives on the neural mechanisms of consciousness and proposes that cortical and thalamo-cortical processing interact at the level of single pyramidal cells. (shrink)

Coordination of immune responses in the gut is a complex task. In order to fight pathogens and maintain a defined population of commensal microbes, the mucosal immune system has to coordinate information from the external (luminal) and internal (abluminal) environment and respond accordingly. Dendritic cells (DCs) are crucial cell types involved in this process as they integrate these signals and direct immunogenic or tolerogenic responses. Here, we review how various functions of DCs depend on microbial stimuli and how (...) these stimuli influence the course of immune activation. (shrink)

Langerhans cells (LCs), residing in the epidermis, are able to induce potent immunogenic responses and also to mediate immune tolerance. We propose that tolerogenic and immunogenic responses of LCs are directed by signaling from the epidermis and involve counter‐acting gene circuits that are coupled to a core maturation gene module. We base our analysis on recent genetic and genomic findings facilitating the understanding of the molecular mechanisms controlling these divergent immune functions. Comparing gene regulatory network (GRN) analyses of various types (...) of dendritic cells (DCs) including LCs we integrate signaling‐dependent (TGFβ, EpCAM, β‐Catenin) and transcription factor (IRF4, IRF1, NFκB) regulated gene circuits that appear to orchestrate the distinctive LC functional states. Our model proposes, that while epidermal signaling in the steady‐state promotes LC tolerogenic function, the disruption of cell‐cell contacts coupled with inflammatory signaling induces LC immunogenic programing. The conceptual framework emphasizes the sensing of discrete epidermal and inflammatory cues by resident LCs in dictating their genomic programing and cell state dynamics. (shrink)

In the mammalian central nervous system (CNS), each neuron receives signals from other neurons through numerous synapses located on its cell body and dendrites. Molecules involved in the postsynaptic signaling pathways need to be targeted to the appropriate subcellular domains at the right time during both synaptogenesis and the maintenance of synaptic functions. The presence of messenger RNAs (mRNAs) in dendrites offers a mechanism for synthesizing the appropriate molecules at the right place in response to local extracellular stimuli. Several (...) dendritic mRNAs have been identified, and the mechanisms controlling their localization are beginning to be understood. In many cell types, controls on mRNA stability play an important role in the regulation of gene expression, but it is unclear to what extent this type of control operates in dendrites. The regulation of protein synthesis and the control of mRNA stability in dendrites could have important implications for neuronal function. BioEssays 20:70–78, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

In the mammalian central nervous system (CNS), each neuron receives signals from other neurons through numerous synapses located on its cell body and dendrites. Molecules involved in the postsynaptic signaling pathways need to be targeted to the appropriate subcellular domains at the right time during both synaptogenesis and the maintenance of synaptic functions. The presence of messenger RNAs (mRNAs) in dendrites offers a mechanism for synthesizing the appropriate molecules at the right place in response to local extracellular stimuli. Several (...) dendritic mRNAs have been identified, and the mechanisms controlling their localization are beginning to be understood. In many cell types, controls on mRNA stability play an important role in the regulation of gene expression, but it is unclear to what extent this type of control operates in dendrites. The regulation of protein synthesis and the control of mRNA stability in dendrites could have important implications for neuronal function. BioEssays 20:70–78, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

The affinities of antibodies (Abs) for their target antigens (Ags) gradually increase in vivo following an infection or vaccination, but reach saturation at values well below those realisable in vitro. This ‘affinity ceiling’ could in many cases restrict our ability to fight infections and compromise vaccines. What determines the affinity ceiling has been an unresolved question for decades. Here, we argue that it arises from the strength of the chain of protein complexes that is pulled by B cells during the (...) process of Ag acquisition. The affinity ceiling is determined by the strength of the weakest link in the chain. We identify the weakest link and show that the resulting affinity ceiling can explain the Ab affinities realized in vivo, providing a conceptual understanding of Ab affinity maturation. We explore plausible evolutionary underpinnings of the affinity ceiling, examine supporting evidence and alternative hypotheses and discuss implications for vaccination strategies. (shrink)

Apoptosis is a physiological mechanism for the removal of unwanted or damaged cells. Apoptotic cells are rarely seen in living tissues, however, because of their rapid and efficient removal by phagocytosis. Phagocytotic cells such as macrophages or dendritic cells recognize apoptotic cells by specific changes of cell surface markers, which usually are not present on normal cells. One such event is the exposure of phosphatidylserine, which moves from the plasma membrane inner leaflet to the outer leaflet in preapoptotic (...) cells. An unresolved problem, however, was the nature of the phosphatidylserine receptor on the phagocytotic cells. In a recent issue of Nature, Fadok et al.(1) have reported the cloning of a phosphatidylserine receptor using an antibody raised against activated macrophages. Antibody treatment of these macrophages blocks this capacity to engulf. BioEssays 22:878–881, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

HIV‐1 infects dendritic cells (DCs) without triggering an effective innate antiviral immune response. As a consequence, the induction of adaptive immune responses controlling virus spread is limited. In a recent issue of Immunity, Lahaye and colleagues show that intricate interactions of HIV capsid with the cellular cofactor cyclophilin A (CypA) control infection and innate immune activation in DCs. Manipulation of HIV‐1 capsid to increase its affinity for CypA results in reduced virus infectivity and facilitates access of the cytosolic DNA (...) sensor cGAS to reverse transcribed DNA. This in turn induces a strong host response. Here, we discuss these findings in the context of recent developments in innate immunity and consider the implications for disease control and vaccine design. (shrink)

Receptors on cytotoxic T lymphocytes and natural killer cells play well‐established roles in the immunological response and share a common ligand in the form of MHC‐I. We discuss how a variety of MHC‐I receptors are also expressed on myelomonocytic cells such as macrophages and dendritic cells. Since myelomonocytic MHC‐I receptors recognise a broad range of alleles and MHC‐I structures, we propose that their task is to discern expression levels and folding forms of MHC. We describe a model in which (...) these recognition events would regulate bidirectional cross talk between cells of innate and adaptive immune systems to organise an ongoing combined immune response. We discuss how such a model is supported by recent literature and might function in a variety of contexts, including immunoregulation during pregnancy. Our model also offers an alternative explanation of immune dysregulation rather than autoimmunity during HLA‐B27‐associated spondyloarthropathies and addresses a number of conundrums in this field. BioEssays 27: 542–550, 2005. © 2005 Wiley periodicals, Inc. (shrink)

Cognition or higher brain activity is sometimes seen as a phenomenon greater than the sum of its parts. This viewpoint however is largely dependent on the state of the art of experimental techniques that endeavor to characterize morphology and its association to function. Retinal ganglion cells are readily accessible for this work and we discuss recent advances in computational techniques in identifying novel parameters that describe structural attributes possibly associated with specific function. These parameters are based on calculating wavelet gradients (...) from cell images followed by the extraction of meaningful measures including 2nd wavelet moment, entropy of orientation, and curvature. For the three cell types analyzed, the mean 2nd wavelet moment, which relates to the field of influence of the dendritic-tree segments was significantly different. cells had the highest mean 2nd wavelet moment, followed by the and cells (134 ± 22, 93 ± 19 and 63 ± 12, respectively). There was no significant difference between cells for entropy of orientation, indicating no class with a preferential orientation of their dendritic tree. Curvature provided similar results to the 2nd wavelet moment with cells having the highest curvature followed by and the cells (mean ± SD: 161 ± 15; 134 ± 22; 121 ± 15). Our feature space analysis also indicated a difference between these cell types. No difference was found between the and cell types and their physiological counterparts the Y and X cells based on wavelet analysis. Both the X and Y cells can be divided into two subtypes, the ON- and OFF-center cells based on the stratification level of the dendritic tree within the retina. Using 2nd wavelet moment, a difference in their morphological attributes, not reported previously, was noted for these subtypes. The 2nd wavelet moment and curvature are further discussed with respect to explaining regularity of spacing and coverage associated with retinal ganglion cell mosaics. (shrink)

The demonstration that dendritic cell (DC)‐derived exosomes can be exploited for targeted RNAi delivery to the brain after systemic injection provides the first proof‐of‐concept for the potential of these naturally occurring vesicles as vehicles of drug delivery. As well as being amenable to existing in vivo targeting strategies already in use for viruses and liposomes, this novel approach offers the added advantages of in vivo safety and low immunogenicity. Fulfilment of the potential of exosome delivery methods warrants a (...) better understanding of their biology, as well as the development of novel production, characterisation, targeting and cargo‐loading nanotechnologies. Ultimately, exosome‐mediated drug delivery promises to overcome important challenges in the field of therapeutics, such as delivery of drugs across otherwise impermeable biological barriers, such as the blood brain barrier, and using patient‐derived tissue as a source of individualised and biocompatible therapeutic drug delivery vehicles. (shrink)

Mononuclear phagocytes (MPs), which consist of dendritic cells, monocytes, and macrophages, are distributed throughout the body and actively eliminate invading microorganisms and abnormal cells. Depending on the local microenvironment, MPs manifest considerably various lifespans and phenotypes to maintain tissue homeostasis. Vascular‐associated mononuclear phagocytes (VaMPs) are the special subsets of MPs that are localized either within the lumen side or on the apical surface of vessels, acting as the critical sentinels to recognize and defend against disseminated tumor cells. In this (...) review, we introduce three major types of VaMPs, patrolling monocytes, Kupffer cells, and perivascular macrophages, and discuss their emerging roles in immunosurveillance during incipient metastasis. We also explore the roles of lineage‐determining transcription factors and cell surface receptors that endow VaMPs with potent anti‐tumor activity. Finally, we highlight the molecular and cellular mechanisms that drive the phenotypic plasticity of VaMPs and summarize combinatory strategies for targeting VaMPs in overt metastasis. (shrink)

Protein turnover (PT) has been formally defined only in equilibrium conditions, which is ill‐suited to quantify PT during dynamic processes that occur during embryogenesis or (extra) cellular signaling. In this Hypothesis, we propose a definition of PT in an out‐of‐equilibrium regime that allows the quantification of PT in virtually any biological context. We propose a simple mathematical and conceptual framework applicable to a broad range of available data, such as RNA sequencing coupled with pulsed‐SILAC datasets. We apply our framework to (...) a published dataset and show that stimulation of mouse dendritic cells with LPS leads to a proteome‐wide change in PT. This is the first quantification of PT out‐of‐equilibrium, paving the way for the analysis of biological systems in other contexts. (shrink)

Vaccines represent preventative interventions amenable to immunogenetic prediction of how human variability will influence their safety and efficacy. The genetic polymorphism among individuals within any population can render possible that the immunity elicited by a vaccine is variable in length and strength. The same immune challenge (virus and/or vaccine) could provoke partial, complete or even failed protection for some individuals treated under the same conditions. We review genetic variants and mechanistic relationships among chemokines, chemokine receptors, interleukins, interferons, interferon receptors, toll‐like (...) receptors, histocompatibility antigens, various immunoglobulins and major histocompatibility complex antigens. These are the targets for variation among macrophages, dendritic cells, natural killer cells, T‐ and B‐lymphocytes, and complement. The technology platforms (mRNA, viral vectors, proteins) utilized to produce vaccines against SARS‐CoV‐2 infections may each trigger genetically distinct immune reactogenic profiles. With DNA biobanking and immunoprofiling of recipients, global COVID‐19 vaccinations could launch a new era of personalized healthcare. (shrink)

_Figure 1. Dendrites and cell bodies of schematic neurons connected by dendritic-dendritic gap junctions form a laterally connected input_ _layer (“dendritic web”) within a neurocomputational architecture. Dendritic web dynamics are temporally coupled to gamma synchrony_ _EEG, and correspond with integration phases of “integrate and fire” cycles. Axonal firings provide input to, and output from, integration_ _phases (only one input, and three output axons are shown). Cell bodies/soma contain nuclei shown as black circles; microtubule networks_ (...) _pervade the cytoplasm. According to the Orch OR theory, gamma EEG-synchronized integration phases include quantum computations in_ _microtubule networks which culminate with conscious moments. Insert closeup shows a gap junction through which microtubule quantum_ _states entangle among different neurons, enabling macroscopic quantum states in dendritic webs extending throughout cortex and other_ _brain regions._. (shrink)

Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis which has infected one third of the mankind and causes 2–3 million deaths worldwide each year. The persistence of the infection ensues from the ability of M. tuberculosis to subvert host immune responses in favor of survival and growth of mycobacteria in macrophages. The mechanisms by which M. tuberculosis manipulates the host immune system have only recently come to light. These activities are attributed to lipoarabinomannans (LAM) and their precursors lipomannans (LM), (...) two predominant glycolipids of M. tuberculosis cell wall. LM are able to skew anti‐mycobacterial immune responses into un‐protective ones, while LAM evoke immunosupression upon binding to macrophage and dendritic cell receptors specialized in binding to “self” host components. A newly emerging idea implicates plasma membrane rafts in LM and LAM signaling. Depending on acylation patterns, the glycolipids may either directly incorporate into the raft membrane via mannosylphosphatidylinositol anchors or interact with raft‐associated proteins to affect the assembly of receptor signaling complexes. BioEssays 30:943–954, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Inflammatory immune cells, when activated, display much the same metabolic profile as a glycolytic tumor cell. This involves a shift in metabolism away from oxidative phosphorylation towards aerobic glycolysis, a phenomenon known as the Warburg effect. The result of this change in macrophages is to rapidly provide ATP and metabolic intermediates for the biosynthesis of immune and inflammatory proteins. In addition, a rise in certain tricarboxylic acid cycle intermediates occurs notably in citrate for lipid biosynthesis, and succinate, which activates (...) the transcription factor Hypoxia‐inducible factor. In this review we take a look at the emerging evidence for a role for the Warburg effect in the immune and inflammatory responses. The reprogramming of metabolic pathways in macrophages, dendritic cells, and T cells could have relevance in the pathogenesis of inflammatory and metabolic diseases and might provide novel therapeutic strategies. (shrink)

This chapter contains section titled: Introduction Theoretical Perspectives Challenges Conclusion References Further Reading.

Mammalian neural cells contain at least two forms of brain spectrin: brain spectrin (240/235) which is located primarily in the axons and presynaptic terminals of neurons, and brain spectrin (240/235E) which is found in the cell bodies, dendrites and postsynaptic terminals of neurones. Brain spectrin (240/235E) is also found in certain glial cell types. Antibodies against red blood cell spectrin detect only brain spectrin (240/235E), while antibodies against brain spectrin isolated from axonal and synaptic membranes detect brain (...) spectrin (240/235). Previous apparent discrepancies in the literature concerning brain spectrin localization at the light microscope level were undoubtedly due to different laboratories detecting distinct brain spectrin subtypes, based on the particular antibody being utilized for immunohistochemistry. In this review we (1) discuss the data supporting the presence of at least two distinct subtypes of mammalian brain spectrin, (2) explain how these results reconcile previous discrepancies concerning the localization of spectrin within neural cells, and (3) suggest the future implications of these findings. (shrink)

Mormyrid teleosts have Purkinje cells with palisade dendrites, which probably represent coincidence detectors of parallel fiber activity. Their existence strongly supports the ideas of Braitenberg et al. on cerebellar function. However, the organization of mormyrid granule cells and parallel fibers suggests that a key to cerebellar function is not in interactions within one wave, but between twoopposite tidal waves.

We present a theoretical view of the cellular foundations for network-level processes involved in producing our conscious experience. Inputs to apical synapses in layer 1 of a large subset of neocortical cells are summed at an integration zone near the top of their apical trunk. These inputs come from diverse sources and provide a context within which the transmission of information abstracted from sensory input to their basal and perisomatic synapses can be amplified when relevant. We argue that apical amplification (...) enables conscious perceptual experience and makes it more flexible, and thus more adaptive, by being sensitive to context. Apical amplification provides a possible mechanism for recurrent processing theory that avoids strong loops. It makes the broadcasting hypothesized by global neuronal workspace theories feasible while preserving the distinct contributions of the individual cells receiving the broadcast. It also provides mechanisms that contribute to the holistic aspects of integrated information theory. As apical amplification is highly dependent on cholinergic, aminergic, and other neuromodulators, it relates the specific contents of conscious experience to global mental states and to fluctuations in arousal when awake. We conclude that apical dendrites provide a cellular mechanism for the context-sensitive selective amplification that is a cardinal prerequisite of conscious perception. (shrink)

The tidal-wave theory is inspired by the particular morphology of the cerebellar cortex. It elegantly attributes function to the anisotropy of the cerebellar wiring and the geometry of Purkinje cell dendrites. In this commentary, physiological considerations are used to elaborate temporal and spatial constraints of the tidal-wave theory. It is shown, first, that limitations of temporal precision in the cortical inputs to the mammalian cerebellum delimit the spatial resolution of an input sequence (i.e., the minimal distance along the parallel (...) fibers which can detect sequential input) to the range of a millimeter at best. Second, temporal characteristics of Purkinje cell postsynaptic potentials are argued to predict a distance of at least several millimeters along the parallel fiber beam in order to generate a sequence in the cerebellar output. It is concluded that the implementation of tidal waves as a general principle of cerebellar function is questionable as there exist cerebelli too small to match these constraints. (shrink)

Early in animal development, gradients of secreted morphogenic molecules, such as Sonic hedgehog (Shh), Wnt and TGFβ/Bmp family members, regulate cell proliferation and determine the fate and phenotype of the target cells by activating well‐characterized signalling pathways, which ultimately control gene transcription. Shh, Wnt and TGFβ/Bmp signalling also play an important and evolutionary conserved role in neural circuit assembly. They regulate neuronal polarization, axon and dendrite development and synaptogenesis, processes that require rapid and local changes in cytoskeletal organization and (...) plasma membrane components. A key question then is whether morphogen signalling at the growth cone uses similar mechanisms and intracellular pathway components to those described for morphogen‐mediated cell specification. This review discusses recent advances towards the understanding of this problem, showing how Shh, Wnt and TGFβ/Bmp have adapted their ‘classical’ signalling pathways or adopted alternative and novel molecular mechanisms to influence different aspects of neuronal circuit formation. (shrink)

In a companion review1 we discussed the data supporting the conclusion that at least two subtypes of spectrin exist in mammalian brain. One form is found in the cell bodies, dendrites, and post‐synaptic terminals of neurons (brain spectrin(240/235E)) and the other subtype is located in the axons and presynaptic terminals (brain spectrin(240/235)). Our recent understanding of brain spectrin subtype localization suggests a possible explanation for a conundrum concerning brain 4.1 localization. Amelin, an immunoreactive analogue of red blood cell (...) (rbc) cytoskeletal protein 4.1, is localized in neuronal cell bodies and dendrites when brain sections are stained with antibody against rbc protein 4.1. However, it has recently been suggested that synapsin I, a neuron‐specific phosphoprotein associated with the cytoplasmic surface of small synaptic vesicles, is related to erythrocyte 4.1. In this review we hypothesize that there are at least two forms of brain 4.1: a cell body/dendritic form (amelin) which is detected with rbc protein 4.1 antibody, and a unique form found exclusively in the presynaptic terminal (synapsin I). The binding of synapsin I to brain spectrin(240/235), and its ability to stimulate the spectrin/F‐actin interaction in a phosphorylation‐dependent manner suggests a model for the regulation of synaptic transmission mediated by the neuronal cytoskeleton. (shrink)

Neurofilaments and microtubules are important components of the neuronal cytoskeleton. In axons or dendrites, these filaments are aligned in parallel arrays, and separated from one another by nonrandom distances. This distinctive organization has been attributed to cross bridges formed by NF side arms or microtubule‐associated proteins. We recently proposed a polymer‐brush‐based mechanism for regulating interactions between neurofilaments and between microtubules. In this model, the side arms of neurofilaments and the projection domains of microtubule‐associated proteins are highly unstructured and exert long‐range (...) repulsive forces that are largely entropic in origin; these forces then act to organize the cytoskeleton in axons and dendrites. Here, we review the biochemical, biophysical, genetic and cell biological data for the polymer‐brush and cross‐bridging models. We explore how the data traditionally used to support cross bridging may be reconciled with a polymer‐brush mechanism and compare the implications of recent experimental insights into axonal transport and physiology for each model. BioEssays 26:1017–1025, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The idea that individual nerve cells might have conscious experiences has been around ever since cells were identified in the seventeenth century, but in the era of modern neuroscience the case for individual human neuronal experience has received little attention. A series of arguments will be presented suggesting that all the human conscious experiences that we talk about are events in individual neurons, not global to the brain or organism. We conclude that cellular consciousness is the only plausible way to (...) explain ‘our’ experiences within current physics and biology, however implausible it might at first seem. This implies that our experiences are multiple in space as well as time, consistent with the neuroscience watchword that there is ‘no single place where everything comes together in the brain’. The central argument is that events of experience must involve rich integration of information and individual neurons are the only places in brains where integration of information occurs. Any more global ‘binding’ is neither required nor physically possible. The detailed nature of events of integration of signals in a neuron’s dendrites remains uncertain but recent developments provide some candidates. (shrink)

Love, fear, hope, calculus, and game shows-how do all these spring from a few delicate pounds of meat? Neurophysiologist Ian Glynn lays the foundation for answering this question in his expansive An Anatomy of Thought, but stops short of committing to one particular theory. The book is a pleasant challenge, presenting the reader with the latest research and thinking about neuroscience and how it relates to various models of consciousness. Combining the aim of a textbook with the style of a (...) popularization, it provides all the lay reader needs to know to participate in the philosophical debate that is redefining our attitudes about our minds. Drawing on the rich history of neurological case studies, Glynn picks through the building blocks of our nervous system, examines our visual and linguistic systems, and probes deeply into our higher thought processes. The stories of great scientists, like Ramon y Cajal, and famous patients, like Sperry's split-brained epileptics, illuminate the scientific issues Glynn selects as essential for understanding consciousness. Some might argue that his lengthy explorations of natural selection overemphasize evolutionary explanations of psychological phenomena, but they must also agree that evolutionary psychology has distanced itself mightily from social Darwinism in recent years and merits a reappraisal. The great consciousness debate may form the core of the 21st-century Zeitgeist; get ready for it with An Anatomy of Thought. -Rob Lightner From Publishers Weekly How do we know? What do we think? How could a philosophical problem-'the mind-body problem,' say-induce a headache? What can evolutionary theory, molecular biology, the history of medicine and experimental psychology tell us about the features of human consciousness, and (once again) how do we know? Glynn, a physician and Cambridge University professor, meticulously attempts to answer these questions and more, setting forth the results of all sorts of research relevant to our brains-from 19th-century dissections to Oliver Sacks-like case studies, work with monkeys and supercomputers, and the enduring puzzles of philosophy, which he rightly saves for near the end. After explaining evolution by natural selection and 'clearing away much dross,' Glynn lays out the experiments and theories that have shown 'how nerve cells can carry information about the body, how they can interact' and how sense organs work; demonstrates the 'mixture of parallel and hierarchical organization' in our brains and 'the striking localization of function within it'; considers where neuroscience is likely to go; and admits that, among the many fields of exciting research just ahead, 'we can be least confident of progress toward a complete, scientific explanation of our sensations and thoughts and feelings.' Other recent explaining-the-brain books have sometimes advanced simplistic, or implausibly grand, claims about the nature and features of consciousness in general. Instead, Glynn offers a patient, informative, well-laid-out researcher's-eye view of what we have learned, how we figured it out and what we still don't know about neurons, senses, feelings, brains and minds. (Apr.) Copyright 2000 Reed Business Information, Inc. From Library Journal The nature of consciousness, which perennially troubles the minds of scientists and philosophers, is the subject of an ever-growing body of literature. Two of the latest entries approach the topic from different perspectives. Glynn, a professor of physiology and head of the Physiological Laboratory at Cambridge, offers a comprehensive summary of what we know about the brain-both its evolution and its mechanisms. Among the topics he covers are natural selection, molecular evolution, nerves and the nervous system, sensory perception, and the specific structures responsible for our intellect. Using the mechanisms involved in vision and speech as models, Glynn skillfully describes various neurological deficiencies that can lead to 'disordered seeing' and problems with the use of language. He carefully distinguishes what we know through experimental evidence from what we know through the observation of patients with neurological damage. He also describes some of the major theories that attempt to explain why these structures arose. While his book concentrates on the structures that make up the mind, Glynn is well aware that some physical events appear explicable only in terms of conscious mental events-a situation that conflicts with the laws of modern physics. Only briefly, however, does he consider the various approaches that have been taken to deal with the issues of mind/body and free will. In contrast, this is the primary focus of The Physics of Consciousness. After reviewing the fundamentals of classic physics, Walker (who has a Ph.D. in physics) summarizes elements of the new physics in which our knowledge of space, time, matter, and energy are all dependent on the moment of observation. Walker explores the meaning of consciousness as a characteristic of the observer. In this context both the observer and the act of measurement are critical. In essence, Walker leads his reader on a journey through his concept of a 'quantum mind,' which can both affect matter (including other minds) and can be affected by other distant matter/minds. To break up what would otherwise be an extremely dense text, Walker also relates the very touching story of the loss of his high-school sweetheart to leukemia. Indeed, it is his memory of their relationship that drives Walker to seek an understanding of ultimate reality. At times, he has a tendency to be dogmatic-as when he concludes, 'our consciousness, our mind, and the will of God are the same mind.' While An Anatomy of Thought is appropriate for most academic libraries, the Physics of Consciousness will be most accessible to readers with some knowledge of advanced physics. -Laurie Bartolini, Illinois State Lib., Springfield Copyright 2000 Reed Business Information, Inc. From Booklist The codiscoverers of natural selection-Charles Darwin and Alfred Wallace-disagreed over the possibility of finding an evolutionary explanation for the human mind. Glynn here argues Darwin's side of the debate, tracing an eons-long path of development starting from simple amino acids floating in primal seas and extending through the erect hominids in which the powers of a massive brain first manifest themselves. Patiently adducing evidence of an evolutionary origin for the underlying molecular machinery, Glynn dissects the nerve centers that make possible speech and hearing, sight, and reading. Pressing deeper, he lays bare the cortical foundations of personality. But those who deal with the mind must attend also to the arguments advanced by philosophers. And it is when he turns from dendrites to syllogisms (especially the vexing mind-body paradox) that Glynn's empirical reasoning fails him. In the end, he concedes his perplexity in trying to conceive of an evolutionary origin for human consciousness. This concession may set the shade of Alfred Wallace to chortling, but it will draw readers into an honest confrontation with a profound enigma. Bryce Christensen. (shrink)

The presence of asymmetry in the human cerebral hemispheres is detectable at both the macroscopic and microscopic scales. The horizontal expansion of cortical surface during development (within individual brains), and across evolutionary time (between species), is largely due to the proliferation and spacing of the microscopic vertical columns of cells that form the cortex. In the asymmetric planum temporale (PT), minicolumn width asymmetry is associated with surface area asymmetry. Although the human minicolumn asymmetry is not large, it is estimated to (...) account for a surface area asymmetry of approximately 9% of the region’s size. Critically, this asymmetry of minicolumns is absent in the equivalent areas of the brains of other apes. The left-hemisphere dominance for processing speech is thought to depend, partly, on a bias for higher resolution processing across widely spaced minicolumns with less overlapping dendritic fields, whereas dense minicolumn spacing in the right hemisphere is associated with more overlapping, lower resolution, holistic processing. This concept refines the simple notion that a larger brain area is associated with dominance for a function and offers an alternative explanation associated with “processing type.” This account is mechanistic in the sense that it offers a mechanism whereby asymmetrical components of structure are related to specific functional biases yielding testable predictions, rather than the generalization that “bigger is better” for any given function. Face processing provides a test case – it is the opposite of language, being dominant in the right hemisphere. Consistent with the bias for holistic, configural processing of faces, the minicolumns in the right-hemisphere fusiform gyrus are thinner than in the left hemisphere, which is associated with featural processing. Again, this asymmetry is not found in chimpanzees. The difference between hemispheres may also be seen in terms of processing speed, facilitated by asymmetric myelination of white matter tracts ( Anderson et al., 1999 found that axons of the left posterior superior temporal lobe were more thickly myelinated). By cross-referencing the differences between the active fields of the two hemispheres, via tracts such as the corpus callosum, the relationship of local features to global features may be encoded. The emergent hierarchy of features within features is a recursive structure that may functionally contribute to generativity – the ability to perceive and express layers of structure and their relations to each other. The inference is that recursive generativity, an essential component of language, reflects an interaction between processing biases that may be traceable in the microstructure of the cerebral cortex. Minicolumn organization in the PT and the prefrontal cortex has been found to correlate with cognitive scores in humans. Altered minicolumn organization is also observed in neuropsychiatric disorders including autism and schizophrenia. Indeed, altered interhemispheric connections correlated with minicolumn asymmetry in schizophrenia may relate to language-processing anomalies that occur in the disorder. Schizophrenia is associated with over-interpretation of word meaning at the semantic level and over-interpretation of relevance at the level of pragmatic competence, whereas autism is associated with overly literal interpretation of word meaning and under-interpretation of social relevance at the pragmatic level. Both appear to emerge from a disruption of the ability to interpret layers of meaning and their relations to each other. This may be a consequence of disequilibrium in the processing of local and global features related to disorganization of minicolumnar units of processing. (shrink)

We propose that a top priority of the cerebral cortex must be the discovery and explicit representation of the environmental variables that contribute as major factors to environmental regularities. Any neural representation in which such variables are represented only implicitly (thus requiring extra computing to use them) will make the regularities more complex and therefore more difficult, if not impossible, to learn. The task of discovering such important environmental variables is not an easy one, since their existence is only indirectly (...) suggested by the sensory input patterns the cortex receives – these variables are “hidden.” We present a candidate computational strategy for (1) discovering regularity-simplifying environmental variables, (2) learning the regularities, and (3) using regularities in perceptual and decision-making tasks. The SINBAD computational model discovers useful environmental variables through a search for different, but nevertheless highly correlated functions of any kind over non-overlapping subsets of the known variables, this being indicative of some important environmental variable that is responsible for the correlation. We suggest that such a search is performed in the neocortex by the dendritic trees of individual pyramidal cells. According to the SINBAD model, the basic function of each pyramidal cell is (1) to discover and represent one of the regularity-simplifying environmental variables, and (2) to learn to infer the state of its variable from the states of other variables, represented by other pyramidal cells. A network of such cells – each cell just attending to representation of its variable – can function as a sophisticated and useful inferential model of the outside world. (shrink)

The present review highlights an association between autism, Alzheimer disease , and fragile X syndrome . We propose a conceptual framework involving the amyloid-beta peptide , Abeta precursor protein , and fragile X mental retardation protein based on experimental evidence. The anabolic effect of the secreted alpha form of the amyloid-beta precursor protein may contribute to the state of brain overgrowth implicated in autism and FXS. Our previous report demonstrated that higher plasma sAPPalpha levels associate with more severe symptoms of (...) autism, including aggression. This molecular effect could contribute to intellectual disability due to repression of cell-cell adhesion, promotion of dense, long, thin dendritic spines, and the potential for disorganized brain structure as a result of disrupted neurogenesis and migration. At the molecular level, APP and FMRP are linked via the metabotropic glutamate receptor 5 . Specifically, mGluR5 activation releases FMRP repression of APP mRNA translation and stimulates sAPP secretion. The relatively lower sAPPalpha level in AD may contribute to AD symptoms that significantly contrast with those of FXS and autism. Low sAPPalpha and production of insoluble Abeta would favor a degenerative process, with the brain atrophy seen in AD. Treatment with mGluR antagonists may help repress APP mRNA translation and reduce secretion of sAPP in FXS and perhaps autism. (shrink)

We argue that prediction success maximization is a basic objective of cognition and cortex, that it is compatible with but distinct from prediction error minimization, that neither objective requires subtractive coding, that there is clear neurobiological evidence for the amplification of predicted signals, and that we are unconvinced by evidence proposed in support of subtractive coding. We outline recent discoveries showing that pyramidal cells on which our cognitive capabilities depend usually transmit information about input to their basal dendrites and amplify (...) that transmission when input to their distal apical dendrites provides a context that agrees with the feedforward basal input in that both are depolarizing, i.e., both are excitatory rather than inhibitory. Though these intracellular discoveries require a level of technical expertise that is beyond the current abilities of most neuroscience labs, they are not controversial and acclaimed as groundbreaking. We note that this cellular cooperative context-sensitivity greatly enhances the cognitive capabilities of the mammalian neocortex, and that much remains to be discovered concerning its evolution, development, and pathology. (shrink)

The shapes of neurons and glial cells dictate many important aspects of their functions. In olfactory systems, certain architectural features are characteristics of these two cell types across a wide variety of species. The accumulated evidence suggests that these common features may play fundamental roles in olfactoryinformation processing. For instance, the primary olfactory neuropil in most vertebrate and invertebrate olfactory systems is organized into discrete modules called glomeruli. Inside each glomerulus, sensory axons and CNS neurons branch and synapse in (...) patterns that are repeated across species. In many species, moreover, the glomeruli are enveloped by a thin and ordered layer of glial processes. Theglomerular arrangement reflects the processing of odor information in modules that encode the discrete molecular attributes of odorant stimuli being processed. Recent studies of the mechanisms that guide the development of olfactory neurons and glial cells have revealed complex reciprocal interactions between these two cell types, which may be necessary for the establishment of modular compartments. Collectively, the findings reviewed here suggest that specialized cellular architecture plays key functional roles in the detection, analysis, and discrimination of odors at early steps in olfactory processing. (shrink)

Excitation at widely dispersed loci in the cerebral cortex may represent a neural correlate of consciousness. Accordingly, each unique combination of excited neurons would determine the content of a conscious moment. This conceptualization would be strengthened if we could identify what orchestrates the various combinations of excited neurons. In the present paper, cholinergic afferents to the cerebral cortex are hypothesized to enhance activity at specific cortical circuits and determine the content of a conscious moment by activating certain combinations of postsynaptic (...) sites in select cortical modules. It is proposed that these selections are enabled by learning-related restructuring that simultaneously adjusts the cytoskeletal matrix at specific constellations of postsynaptic sites giving all a similar geometry. The underlying mechanism of conscious awareness hypothetically involves cholinergic mediation of linkages between microtubules and microtubule-associated protein-2 . The first reason for proposing this mechanism is that previous studies indicate cognitive-related changes in MAP-2 occur in cholinoceptive cells within discrete cortical modules. These cortical modules are found throughout the cerebral cortex, measure 1–2 mm2, and contain approximately 103–104cholinoceptive cells that are enriched with MAP-2. The subsectors of the hippocampus may function similarly to cortical modules. The second reason for proposing the current mechanism is that the MAP-2 rich cells throughout the cerebral cortex correspond almost exactly with the cortical cells containing muscarinic receptors. Many of these cholinoceptive, MAP-2 rich cells are large pyramidal cell types, but some are also small pyramidal cells and nonpyramidal types. The third reason for proposing the current mechanism is that cholinergic afferents are module-specific; cholinergic axons terminate wholly within individual cortical modules. The cholinergic afferents may be unique in this regard. Finally, the tapering apical dendrites of pyramidal cells are proposed as primary sites for cholinergic mediation of linkages between MAP-2 and microtubules because especially high amounts of MAP-2 are found here. Also, the possibility is raised that muscarinic actions on MAP-2 could modulate microtubular coherence and self-collapse, phenomena that have been suggested to underlie consciousness. (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)

In the beginning of the 20th century the groundbreaking work of Ramon y Cajal firmly established the neuron doctrine, according to which neurons are the basic structural and functional units of the nervous system. Von Weldeyer coined the term “neuron” in 1891, but the huge leap forward in neuroscience was due to Cajal’s meticulous microscopic observations of brain sections stained with an improved version of Golgi’s la reazione nera (black reaction). The latter improvement of Golgi’s technique made it possible to (...) visualize the arborizations of single neurons that were “colored brownish black even to their finest branchlets, standing out with unsurpassable clarity upon a transparent yellow background. All was sharp as a sketch with Chinese ink”. The high quality of both the visualization of individual nerve cells and the work performed on studying the anatomy of the central nervous system lead Ramon y Cajal to the conclusion that axons output the nervous impulses to the dendrites or the soma of other target neurons. (shrink)

The ability to predict is the most importantability of the brain. Somehow, the cortex isable to extract regularities from theenvironment and use those regularities as abasis for prediction. This is a most remarkableskill, considering that behaviourallysignificant environmental regularities are noteasy to discern: they operate not only betweenpairs of simple environmental conditions, astraditional associationism has assumed, butamong complex functions of conditions that areorders of complexity removed from raw sensoryinputs. We propose that the brain's basicmechanism for discovering such complexregularities is implemented in (...) the dendritictrees of individual pyramidal cells in thecerebral cortex. Pyramidal cells have 5–8principal dendrites, each of which is capableof learning nonlinear input-to-outputtransfer functions. We propose that eachdendrite is trained, in learning its transferfunction, by all the other principal dendritesof the same cell. These dendrites teach eachother to respond to their separate inputs with matching outputs. Exposed to differentbut related information about the sensoryenvironment, principal dendrites of the samecell tune to functions over environmentalconditions that, while different, are correlated . As a result, the cell as awhole tunes to the source of the regularitiesdiscovered by the cooperating dendrites,creating a new representation. When organizedinto feed-forward/feedback layers, pyramidalcells can build their discoveries on thediscoveries of other cells, graduallyuncovering nature's hidden order. Theresulting associative network is powerfulenough to meet a troubling traditionalobjection to associationism: that it is toosimple an architecture to implement rationalprocesses. (shrink)

Among emotions, surprise has been extensively studied in psychology. In linguistics, surprise, like other emotions, has mainly been studied through the syntactic patterns involving surprise lexemes. However, little has been done so far to correlate the reaction of surprise investigated in psychological approaches and the effects of surprise on language. This cross-disciplinary volume aims to bridge the gap between emotion, cognition and language by bringing together nine contributions on surprise from different backgrounds - psychology, human-agent interaction, linguistics. Using different methods (...) at different levels of analysis, all contributors concur in defining surprise as a cognitive operation and as a component of emotion rather than as a pure emotion. Surprise results from expectations not being met and is therefore related to epistemicity. Linguistically, there does not exist an unequivocal marker of surprise. Surprise may be either described by surprise lexemes, which are often associated with figurative language, or it may be expressed by grammatical and syntactic constructions. Originally published as a special issue of Review of Cognitive Linguistics 13:2 (2015). (shrink)

Nous étudions dans cet article les différentes formes de prédication seconde détachée en position initiale dans un corpus comparable composé de textes d’économie en anglais et en français. Ce corpus a été annoté sous le logiciel Analec. L’enjeu est de montrer en quoi un même phénomène syntaxique est exploité, sur le plan discursif, de façon divergente dans chacune des deux langues. Une étude qualitative et quantitative des prédications secondes du corpus montre que la prédication seconde prend le plus souvent la (...) forme d’une participiale en –ing en anglais, où elle se spécialise dans un rôle méta-énonciatif de balise textuelle pour le lecteur, ce qui n’est pas le cas en français. (shrink)

This study presents a sociological profile of Peruvian female industrialists and some narratives of their struggle for personal independence and entrepreneurial success within the context of global restructuring and local deindustrialization. The study adopts the classical definition of woman's economic independence as a result of women's participation in the world of paid labor.