Brain arteriovenous malformations (bAVMs) are abnormal vessels that are prone to rupture, causing life-threatening intracranial bleeding. The mechanism of bAVM formation is poorly understood. Nevertheless, animal studies revealed that gene mutation in endothelial cells (ECs) and angiogenic stimulation are necessary for bAVM initiation. Evidence collected through analyzing bAVM specimens of human and mouse models indicate that cells other than ECs also are involved in bAVM pathogenesis. Both human and mouse bAVMs vessels showed lower mural cell-coverage, suggesting a role of (...) pericytes and vascular smooth muscle cells (vSMCs) in bAVM pathogenesis. Perivascular astrocytes also are important in maintaining cerebral vascular function and take part in bAVM development. Furthermore, higher inflammatory cytokines in bAVM tissue and blood demonstrate the contribution of inflammatory cells in bAVM progression, and rupture. The goal of this paper is to provide our current understanding of the roles of different cellular loci in bAVM pathogenesis. (shrink)

How does your mind work? How does your brain give rise to your mind? These are questions that all of us have wondered about at some point in our lives, if only because everything that we know is experienced in our minds. They are also very hard questions to answer. After all, how can a mind understand itself? How can you understand something as complex as the tool that is being used to understand it? This book provides an introductory (...) and self-contained description of some of the exciting answers to these questions that modern theories of mind and brain have recently proposed. Stephen Grossberg is broadly acknowledged to be the most important pioneer and current research leader who has, for the past 50 years, modelled how brains give rise to minds, notably how neural circuits in multiple brain regions interact together to generate psychological functions. This research has led to a unified understanding of how, where, and why our brains can consciously see, hear, feel, and know about the world, and effectively plan and act within it. The work embodies revolutionary Principia of Mind that clarify how autonomous adaptive intelligence is achieved. It provides mechanistic explanations of multiple mental disorders, including symptoms of Alzheimer's disease, autism, amnesia, and sleep disorders; biological bases of morality and religion, including why our brains are biased towards the good so that values are not purely relative; perplexing aspects of the human condition, including why many decisions are irrational and self-defeating despite evolution's selection of adaptive behaviors; and solutions to large-scale problems in machine learning, technology, and Artificial Intelligence that provide a blueprint for autonomously intelligent algorithms and robots. Because brains embody a universal developmental code, unifying insights also emerge about shared laws that are found in all living cellular tissues, from the most primitive to the most advanced, notably how the laws governing networks of interacting cells support developmental and learning processes in all species. The fundamental brain design principles of complementarity, uncertainty, and resonance that Grossberg has discovered also reflect laws of the physical world with which our brains ceaselessly interact, and which enable our brains to incrementally learn to understand those laws, thereby enabling humans to understand the world scientifically. Accessibly written, and lavishly illustrated, Conscious Mind/Resonant Brain is the magnum opus of one of the most influential scientists of the past 50 years, and will appeal to a broad readership across the sciences and humanities. (shrink)

The target article on cellular mechanisms of long-term depression appears to have been well received by most authors of the relevant commentaries. This may be due to the fact that this review aimed to give a general account of the topic, rather than just describe previous work of the present author. The present response accordingly only raises questions of major interest for future research.

Alzheimer's disease results from the degeneration of neurons. Degenerating nerve cells express atypical proteins, and amyloid is deposited. We suggest that some of these events are strongly influenced by genetic factors and age. Animal models should be useful in investigating the pathogenic mechanisms that lead to the brain abnormalities seen in this disease.

Cellular mechanisms hypothesized to underlie sleep-dependent memory consolidation are expressed throughout the brain during sleep. Use of sleep deprivation to evaluate the functional importance of these mechanisms is confounded by degradation in waking performance resulting from impaired vigilance. There is a need for methods that will permit disruption of specific mechanisms during sleep only in the neuronal circuits most critically involved in learning. This should be accomplished without global sleep disruption and with preservation of the restorative aspects of (...) sleep. (shrink)

The brain ventricular system is a series of connected cavities, filled with cerebrospinal fluid (CSF), that forms within the vertebrate central nervous system (CNS). The hollow neural tube is a hallmark of the chordate CNS, and a closed neural tube is essential for normal development. Development and function of the ventricular system is examined, emphasizing three interdigitating components that form a functional system: ventricle walls, CSF fluid properties, and activity of CSF constituent factors. The cellular lining of the (...) ventricle both can produce and is responsive to CSF. Fluid properties and conserved CSF components contribute to normal CNS development. Anomalies of the CSF/ventricular system serve as diagnostics and may cause CNS disorders, further highlighting their importance. This review focuses on the evolution and development of the brain ventricular system, associated function, and connected pathologies. It is geared as an introduction for scholars with little background in the field. (shrink)

We understand the workings of the human body as a series of interdependent physiological relationships: muscle interacts with bone as the heart responds to hormones secreted by the brain, all the way down to the inner workings of every cell. To make an organism function, no one component can work alone. In light of this, why is it that the accepted understanding that the physical phenomenon of the mind is attributed only to the brain? In The Embodied Mind, (...) internationally renowned psychiatrist Dr. Thomas R. Verny sets out to redefine our concept of the mind and consciousness. He brilliantly compiles new research that points to the mind's ties to every part of the body. The Embodied Mind collects disparate findings in physiology, genetics, and quantum physics in order to illustrate the mounting evidence that somatic cells, not just neural cells, store memory, inform genetic coding, and adapt to environmental changes-all behaviors that contribute to the mind and consciousness. Cellular memory, Verny shows, is not just an abstraction, but a well-documented scientific fact that will shift our understanding of memory. Verny describes single-celled organisms with no brains demonstrating memory, and points to the remarkable case of a French man who, despite having a brain just a fraction of the typical size, leads a normal life with a family and a job. The Embodied Mind shows how intelligence and consciousness-traits traditionally attributed to the brain alone-also permeate our entire being. Bodily cells and tissues use the same molecular mechanisms for memory as our brain, making our mind more fluid and adaptable than we could have ever imaged. (shrink)

A conscious moment occurs when an individual is in a state of awareness of one’s self and the external environment. The human brain has been extensively studied to understand the phenomena of human thought and behavior in the context of consciousness. Consciousness has always been linked to the nervous system but there are several studies that have recorded conscious behaviours in organisms without nerve cells. This paper hypothesizes that quantum energy generated consciousness emerges in each and every living cell (...) and traverses by means of electromagnetic radiation; an oldest form of energy that exist in the cosmos and which utilizes the cellular structures to flow by means of a coherent, invisible, powerful, recyclable process; a connection with the cosmic energy bridge. (shrink)

Computational neuroscientists not only employ computer models and simulations in studying brain functions. They also view the modeled nervous system itself as computing. What does it mean to say that the brain computes? And what is the utility of the ‘brain-as-computer’ assumption in studying brain functions? In previous work, I have argued that a structural conception of computation is not adequate to address these questions. Here I outline an alternative conception of computation, which I call the (...) analog-model. The term ‘analog-model’ does not mean continuous, non-discrete or non-digital. It means that the functional performance of the system simulates mathematical relations in some other system, between what is being represented. The brain-as-computer view is invoked to demonstrate that the internal cellular activity is appropriate for the pertinent information-processing task.Keywords: Computation; Computational neuroscience; Analog computers; Representation; Simulation. (shrink)

The data on the cellular mechanism of LTD that is presented in four target articles is synthesized into a new model of Purkinje cell plasticity. This model attempts to address credit assignment problems that are crucial in learning systems. Intracellular signal transduction mechanisms may provide the mechanism for a 3-factor learning rule and a trace mechanism. The latter may permit delayed information about motor error to modify the prior synaptic events that caused the error. This model may help to (...) focus future cellular studies on issues that are particularly critical for a computationally viable concept of cerebellar plasticity, [CRÉPEL et al.; HOUK et al.; KANO; LINDEN; VINCENT]. (shrink)

First of all, we would like to gratefully thank all commentators for the attention and effort they have put into reading and responding to our review paper [this issue] and for useful observations that suggest novel applications for our framework. We understand and accept that some of our claims might appear controversial and raise skepticism, because the overall neural framework we have proposed is difficult to frame in established categories, given its strong multidisciplinary character. To make an example, Elsevier is (...) publishing the British Neuroscience Association (BNA) 2017 Special Issue Collection. However, our paper could not fully fit in any of their Special Issues—attention, motivation, behavior; sensory and motor systems; novel treatments and translational neuroscience; genetics and epigenetics; learning and memory; neurodegenerative disorders and ageing; developmental neuroscience; neuronal, glial and cellular mechanisms; neuroendocrine and autonomic nervous systems; psychiatry and mental health; methods and techniques. Perhaps because our paper was mathematically, physically, biologically (neuroscientifically), and phenomenologically motivated from the start? Nevertheless, venturing in novel, fresh, testable proposals is badly needed in contemporary neuroscience, so to break into “the utter darkness of the inner mechanism of psychic acts… during the production of the concomitant phenomena of perception and thought, namely, feelings, consciousness and volition”—as Cajal had already observed in his opus magnus ‘Textura’. But as he soberly confessed: “This ideal is still very distant” (Ramon y Cajal, 1899-1904, p. 1,141). In the pursuit of that very ideal, neuroscience and psychology have had, and continue to have, a plethora of movements and schools of thought: behaviorism, cognitivism, neural Darwinism, social constructivism, Bayesian optimization...In our paper, we propose to go a step further, via the notion of topodynamics, towards “projectionism.” In what follows, trying to elucidate the main features of this Emperor’s new clothing, we proceed with the responses to the comments received. (shrink)

Enhancing the usability of the brain, as a more intriguing alloy for interaction design, by employing the Brain Current Interface model (BCIm). Instead of studying interaction design through the angle of cognitive semiotics, where signs and signifiers produce meaning, I propose, in this case, to approach the paradigm of interaction design from a metaphorical angle, as a product of perceptual and intentional consciousness. Through this disposition, I argue, it is possible to approach the hypothesis of bringing together the (...) use of non-invasive brain computer interfaces (BCI) and the field of contemporary neuroscience, especially the role of the chemical modulation on a cellular level of the brain while learning, in order to propose a model for interaction via deliberate attention, that influences cognitive performance and advances well-being of individuals of any age.That which was previously mentally projected, which was lived as a metaphor in the terrestrial habitat is from now on projected entirely without metaphor …. (shrink)

Consciousness has always been linked to the nervous system or rather the brain, but there recorded conscious behaviors in organisms without nerve cells have changed the perspective of consciousness. A living cell is a blend of resonant frequencies, due to degrees of freedom that make it vibrate as a harmonic oscillator supporting the progression of vibrations as waves in and out of the system; to the neighboring cells, to the body, to other bodies and ultimately to the Universe; all (...) of which connects. Quantum generated consciousness is energy; emerges in each and every living cell and traverses by means of resonating vibrations; which utilizes the cellular structures to flow by means of a coherent, obscured, robust, recoverable process. (shrink)

Mathematical models of tumour invasion appear as interesting tools for connecting the information extracted from medical imaging techniques and the large amount of data collected at the cellular and molecular levels. Most of the recent studies have used stochastic models of cell translocation for the comparison of computer simulations with histological solid tumour sections in order to discriminate and characterise expansive growth and active cell movements during host tissue invasion. This paper describes how a deterministic approach based on reaction-diffusion (...) models and their generalisation in the mechano-chemical framework developed in the study of biological morphogenesis can be an alternative for analysing tumour morphological patterns. We support these considerations by reviewing two studies. In the first example, successful comparison of simulated brain tumour growth with a time sequence of computerised tomography (CT) scans leads to a quantification of the clinical parameters describing the invasion process and the therapy. The second example considers minimal hypotheses relating cell motility and cell traction forces. Using this model, we can simulate the bifurcation from an homogeneous distribution of cells at the tumour surface toward a nonhomogeneous density pattern which could characterise a pre-invasive stage at the tumour-host tissue interface. (shrink)

In the present paper we formulate the hypothesis that brain glycogen is a critical determinant in the modulation of carbohydrate supply at the cellular level. Specifically, we propose that mobilization of astrocytic glycogen after an increase in AMP levels during enhanced neuronal activity controls the concentration of glucose phosphates in astrocytes. This would result in modulation of glucose phosphorylation by hexokinase and upstream cell glucose uptake. This mechanism would favor glucose channeling to activated neurons, supplementing the already rich (...) neuron‐astrocyte metabolic and functional partnership with important implications for the energy compounds used to sustain neuronal activity. The hypothesis is based on recent modeling evidence suggesting that rapid glycogen breakdown can profoundly alter the short‐term kinetics of glucose delivery to neurons and astrocytes. It is also based on review of the literature relevant to glycogen metabolism during physiological brain activity, with an emphasis on the metabolic pathways identifying both the origin and the fate of this glucose reserve. (shrink)

As opposed to the dismissive attitude toward reductionism that is popular in current philosophy of mind, a “ruthless reductionism” is alive and thriving in “molecular and cellular cognition”—a field of research within cellular and molecular neuroscience, the current mainstream of the discipline. Basic experimental practices and emerging results from this field imply that two common assertions by philosophers and cognitive scientists are false: (1) that we do not know much about how the brain works, and (2) that (...) lower-level neuroscience cannot explain cognition and complex behavior directly. These experimental practices involve intervening directly with molecular components of sub-cellular and gene expression pathways in neurons and then measuring specific behaviors. These behaviors are tracked using tests that are widely accepted by experimental psychologists to study the psychological phenomenon at issue (e.g., memory, attention, and perception). Here I illustrate these practices and their importance for explanation and reduction in current mainstream neuroscience by describing recent work on social recognition memory in mammals. (shrink)

Vertebrates respond to light with more than just their eyes. In this article, we speculate on the intriguing possibility that a link remains between non‐visual opsins and neurohormonal systems that control neuronal circuit formation and activity in mammals. Historically, the retina and pineal gland were considered the only significant light‐sensing tissues in vertebrates. However over the last century, evidence has accumulated arguing that extra‐ocular tissues in vertebrates influence behavior through non‐image‐forming photoreception. One such class of extra‐ocular light detectors are the (...) long mysterious deep brain photoreceptors. Here, we review recent findings on the cellular identity and the function of deep brain photoreceptors controlling behavior and physiology in zebrafish, and discuss their implications. (shrink)

I go deep into the biology of the human organism to argue that the psychological features and functions of persons are realized by cellular and molecular parallel distributed processing networks dispersed throughout the whole body. Persons supervene on the computational processes of nervous, endocrine, immune, and genetic networks. Persons do not go with brains.

Vertebrates respond to light with more than just their eyes. In this article, we speculate on the intriguing possibility that a link remains between non‐visual opsins and neurohormonal systems that control neuronal circuit formation and activity in mammals. Historically, the retina and pineal gland were considered the only significant light‐sensing tissues in vertebrates. However over the last century, evidence has accumulated arguing that extra‐ocular tissues in vertebrates influence behavior through non‐image‐forming photoreception. One such class of extra‐ocular light detectors are the (...) long mysterious deep brain photoreceptors. Here, we review recent findings on the cellular identity and the function of deep brain photoreceptors controlling behavior and physiology in zebrafish, and discuss their implications. (shrink)

The neuroanatomical substrates controlling and regulating sleeping and waking, and thus consciousness, are located in the brain stem. Most crucial for bringing the brain into a state conducive for consciousness and information processing is the mesencephalic part of the brain stem. This part controls the state of waking, which is generally associated with a high degree of consciousness. Wakefulness is accompanied by a low-amplitude, high-frequency electroencephalogram, due to the fact that thalamocortical neurons fire in a state of (...) tonic depolarization. Information can easily pass the low-level threshold of these neurons, leading to a high transfer ratio. The complexity of the electroencephalogram during conscious waking is high, as expressed in a high correlation dimension. Accordingly, the level of information processing is high. Spindles, and alpha waves in humans, mark the transition from wakefulness to sleep. These phenomena are related to drowsiness, associated with a reduction in consciousness. Drowsiness occurs when cells undergo moderate hyperpolarizations. Increased inhibitions result in a reduction of afferent information, with a lowered transfer ratio. Information processing subsides, which is also expressed in a diminished correlation dimension. Consciousness is further decreased at the onset of slow wave sleep. This sleep is controlled by the medullar reticular formation and is characterized by a high-voltage, low-frequency electroencephalogram. Slow wave sleep becomes manifest when neurons undergo a further hyperpolarization. Inhibitory activities are so strong that the transfer ratio further drops, as does the correlation dimension. Thus, sensory information is largely blocked and information processing is on a low level. Finally, rapid eye movement sleep is regulated by the pontine reticular formation and is associated with a ''wake-like'' electroencephalographic pattern. Just as during wakefulness, this is the expression of a depolarization of thalamocortical neurons. The transfer ratio of rapid eye movement sleep has not yet been determined, but seems to vary. Evidence exists that this type of sleep, associated with dreaming, with some kind of perception and consciousness, is involved in processing of ''internal'' information. In line with this, rapid eye movement sleep has higher correlation dimensions than slow-wave sleep and sometimes even higher than wakefulness. It is assumed that the ''near-the-threshold'' depolarized state of neurons in the thalamus and cerebral cortex is a necessary condition for perceptual processes and consciousness, such as occurs during waking and in an altered form during rapid eye movement sleep. (shrink)

Revonsuo argues that current brain imaging methods do not allow us to ‘discover’ consciousness. While all observational methods in science have limitations, consciousness is such a massive and pervasive phenomenon that we cannot fail to observe its effects at every level of brain organization: molecular, cellular, electrical, anatomical, metabolic, and even the ‘higher levels of electrophysiological organization that are crucial for the empirical discovery and theoretical explanation of consciousness’ . Indeed, the first major discovery in that respect (...) was Hans Berger's finding that scalp EEG is massively different between waking and deep sleep, already seven decades ago. We now have perhaps a dozen sophisticated methods for monitoring consciousness-related activity at multiple levels of brain observation. Theoretical progress has come quite rapidly. Recently, E.R. John and colleagues have made fundamental findings using Quantitative EEG, showing consistent brainwide changes as a result of several types of general anaesthetics . John has proposed a neuronal ‘field theory’ to account for those results. Another promising new method involves frequency-tagging of competing stimuli, allowing us to follow the activity of billions of neurons synchronized to particular conscious stimuli, always compared to very similar unconscious input . A fundamental theoretical account of such results has been provided by Tononi & Edelman . Such results and theory are in broad agreement with the cognitive theory proposed by Baars. (shrink)

The well-established techniques of the professional storyteller not only have the potential to model complex “truth” but also to dig deeply into that complexity, thereby perhaps getting closer to that truth. This applies not only to fiction, but also to medicine and even science. Compelling storytelling ability may have conferred an evolutionary survival advantage and, if so, is likely represented in the neural circuitry of the human brain. Functional imaging will likely point to a neuroanatomical basis for compelling storytelling (...) ability; this will presumably reflect underlying cellular and molecular mechanisms. (shrink)

The cerebral cortex controls our most distinguishing higher cognitive functions. Human‐specific gene expression differences are abundant in the cerebral cortex, yet we have only begun to understand how these variations impact brain function. This review discusses the current evidence linking non‐coding regulatory DNA changes, including enhancers, with neocortical evolution. Functional interrogation using animal models reveals converging roles for our genome in key aspects of cortical development including progenitor cell cycle and neuronal signaling. New technologies, including iPS cells and organoids, (...) offer potential alternatives to modeling evolutionary modifications in a relevant species context. Several diseases rooted in the cerebral cortex uniquely manifest in humans compared to other primates, thus highlighting the importance of understanding human brain differences. Future studies of regulatory loci, including those implicated in disease, will collectively help elucidate key cellular and genetic mechanisms underlying our distinguishing cognitive traits. (shrink)

Mutations in growth factor receptor signaling pathways are common in cancer cells, including the highly lethal brain tumor glioblastoma (GBM) where they drive tumor growth through mechanisms including altering the uptake and utilization of nutrients. However, the impact of changes in micro‐environmental nutrient levels on oncogenic signaling, tumor growth, and drug resistance is not well understood. We recently tested the hypothesis that external nutrients promote GBM growth and treatment resistance by maintaining the activity of mechanistic target of rapamycin complex (...) 2 (mTORC2), a critical intermediate of growth factor receptor signaling, suggesting that altered cellular metabolism is not only a consequence of oncogenic signaling, but also potentially an important determinant of its activity. Here, we describe the studies that corroborate the hypothesis and propose others that derive from them. Notably, this line of reasoning raises the possibility that systemic metabolism may contribute to responsiveness to targeted cancer therapies. (shrink)

A unifying theory of general anesthetic-induced unconsciousness must explain the common mechanism through which various anesthetic agents produce unconsciousness. Functional-brain-imaging data obtained from 11 volunteers during general anesthesia showed specific suppression of regional thalamic and midbrain reticular formation activity across two different commonly used volatile agents. These findings are discussed in relation to findings from sleep neurophysiology and the implications of this work for consciousness research. It is hypothesized that the essential common neurophysiologic mechanism underlying anesthetic-induced unconsciousness is, as (...) with sleep-induced unconsciousness, a hyperpolarization block of thalamocortical neurons. A model of anesthetic-induced unconsciousness is introduced to explain how the plethora of effects anesthetics have on cellular functioning ultimately all converge on a single neuroanatomic/neurophysiologic system, thus providing for a unitary physiologic theory of narcosis related to consciousness. (shrink)

Hippocampal neurogenesis has been implicated in the pathogenesis of and recovery from depression. However, most of the underlying studies were endpoint investigations in experimental animals yielding conflicting results, and it has been under debate to which extent these results could be transferred to human patients. Now, researchers have developed a powerful new tool to address these questions by a non‐invasive method in humans and animals in vivo, using magnetic resonance spectroscopy to detect a biomarker for proliferating progenitor cells that give (...) rise to new neurons.1 This makes it possible to study the role of neural progenitor cells in a wide variety of human brain disorders. BioEssays 30:806–810, 2008. © 2008 Wiley Periodicals, Inc. (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)

Robert Brain traces the origins of artistic modernism to specific technologies of perception developed in late-nineteenth-century laboratories. Brain argues that the thriving fin-de-siècle field of “physiological aesthetics,” which sought physiological explanations for the capacity to appreciate beauty and art, changed the way poets, artists, and musicians worked and brought a dramatic transformation to the idea of art itself.

Pericytes, like vascular smooth muscle cells, are perivascular cells closely associated with blood vessels throughout the body. Pericytes are necessary for vascular development and homeostasis, with particularly critical roles in the brain, where they are involved in regulating cerebral blood flow and establishing the blood-brain barrier. A role for pericytes during neurovascular disease pathogenesis is less clear—while some studies associate decreased pericyte coverage with select neurovascular diseases, others suggest increased pericyte infiltration in response to hypoxia or traumatic (...) class='Hi'>brain injury. Here, we used an endothelial loss-of-function Recombination signal binding protein for immunoglobulin kappa J region (Rbpj)/Notch mediated mouse model of brain arteriovenous malformation (AVM) to investigate effects on pericytes during neurovascular disease pathogenesis. We tested the hypothesis that pericyte expansion, via morphological changes, and Platelet-derived growth factor B/Platelet-derived growth factor receptor β (Pdgf-B/Pdgfrβ)-dependent endothelial cell-pericyte communication are affected, during the pathogenesis of Rbpj mediated brain AVM in mice. Our data show that pericyte coverage of vascular endothelium expanded pathologically, to maintain coverage of vascular abnormalities in brain and retina, following endothelial deletion of Rbpj. In Rbpj-mutant brain, pericyte expansion was likely attributed to cytoplasmic process extension and not to increased pericyte proliferation. Despite expanding overall area of vessel coverage, pericytes from Rbpj-mutant brains showed decreased expression of Pdgfrβ, Neural (N)-cadherin, and cluster of differentiation (CD)146, as compared to controls, which likely affected Pdgf-B/Pdgfrβ-dependent communication and appositional associations between endothelial cells and pericytes in Rbpj-mutant brain microvessels. By contrast, and perhaps by compensatory mechanism, endothelial cells showed increased expression of N-cadherin. Our data identify cellular and molecular effects on brain pericytes, following endothelial deletion of Rbpj, and suggest pericytes as potential therapeutic targets for Rbpj/Notch related brain AVM. (shrink)

Since the early 2000s, authoritarianism has risen as an increasingly powerful global phenomenon. This shift has not only social and political implications, but environmental implications too: authoritarian leaders seek to recast the relationship between society and the government in every aspect of public life, including environmental policy. When historians of technology or the environment have investigated the environmental consequences of authoritarian regimes, they have frequently argued that authoritarian regimes have been unable to produce positive environmental results or adjust successfully to (...) global structural change, if they have shown any concern for the environment at all. Put another way, the scholarly consensus holds that authoritarian regimes on both the left and the right generally have demonstrated an anti-environmentalist bias, and when opposed by environmentalist social movements, have succeeded in silencing those voices. This book explores the theme of environmental politics and authoritarian regimes on both the right and the left. The authors argue that in instances when environmentalist policies offer the possibility of bolstering a country's domestic (nationalist) appeal or its international prestige, authoritarian regimes can endorse and have endorsed environmental protective measures. The collection of essays analyse environmentalist initiatives pursued by authoritarian regimes, and provide explanations for both the successes and failures of such regimes. Looking at a range of case studies from a number of countries, including Brazil, China, Poland and Zimbabwe. (shrink)

Determining the brain properties that make people ‘brainier’ has moved well beyond early demonstrations that increasing intelligence correlates with increasing grey and white matter volumes. Both structural and functional in vivo neuroimaging techniques delineate a distributed network of brain regions, perhaps with a focus in the lateral prefrontal cortex, which varies in extent and connectivity with individual differences in intelligence. Longitudinal studies further show that the neuroanatomic correlates of intelligence are dynamic, changing most rapidly in early childhood. Several (...) promising candidate genes affecting neuronal development and neurotransmission have been proposed that might begin to explain the marked genetic overlap between cortical morphology and intelligence. A major future challenge is to determine the cellular events that underpin the neuroanatomic differences correlated with intelligence. BioEssays 29:962–973, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

The recent finding that the human version of a neurodevelopmental enhancer of the Wnt receptor Frizzled 8 (FZD8) gene alters neural progenitor cell cycle timing and brain size is a step forward to understanding human brain evolution. The human brain is distinctive in terms of its cognitive abilities as well as its susceptibility to neurological disease. Identifying which of the millions of genomic changes that occurred during human evolution led to these and other uniquely human traits is (...) extremely challenging. Recent studies have demonstrated that many of the fastest evolving regions of the human genome function as gene regulatory enhancers during embryonic development and that the human‐specific mutations in them might alter expression patterns. However, elucidating molecular and cellular effects of sequence or expression pattern changes is a major obstacle to discovering the genetic bases of the evolution of our species. There is much work to do before human‐specific genetic and genomic changes are linked to complex human traits. (shrink)

During the formation of the brain, neuronal cell migration and neurite extension are controlled by extracellular guidance cues. Here, I discuss experiments showing that the messenger nitric oxide (NO) is an additional regulator of cell motility. NO is a membrane permeant molecule, which activates soluble guanylyl cyclase (sGC) and leads to the formation of cyclic GMP (cGMP) in target cells. The analysis of specific cells types in invertebrate models such as molluscs, insects and the medicinal leech provides insight how (...) NO and cyclic nucleotides affect the wiring of nervous systems by regulating cell and growth‐cone motility. Inhibition of the NOS and sGC enzymes combined with rescue experiments show that NO signalling orchestrates neurite outgrowth and filopodial dynamics, cell migration of enteric neurons, glial migration and axonogenesis of pioneer fibers. Cultured insect embryos are accessible model systems in which cellular mechanisms of NO‐induced cytoskeletal reorganizations can be analyzed in natural settings. Finally, I will outline some indications that NO may also regulate cell motility in the developing and regenerating vertebrate nervous system. BioEssays 27:495–505, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Stem cells isolated from adult mammalian tissues may provide new approaches for the autologous treatment of disease and tissue repair. Although the potential of adult stem cells has received much attention, it has also recently been brought into question. This article reviews the recent work describing the ability of non‐hematopoietic stem cells derived from adult bone marrow to form neural derivatives and their potential for brain repair. Earlier transplantation experiments imply that grafted adult stem cells can differentiate into neural (...) derivatives. Recent reports suggest, however, that such findings may be misleading and grafted cells acquiring different identities may merely be explained by their fusion with host cells and not the result of radical changes to their program of cellular differentiation. Nonetheless, in vitro studies have shown that neural development by bone‐marrow‐derived stem cells also appears possible. Understanding the molecular mechanisms that specify the neural lineage will lead to the development of tools for the targeted production of neural cell types in vitro that may ultimately provide a source of material to treat specific neurological deficits. BioEssays 24:708–713, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

LTP is thought to be an experimental model for studying the cellular mechanism of learning and memory. Shors & Matzel review some contradictory data concerning the linkage between LTP and memory and suggest that LTP does not underlie learning and memory. LTP is a cellular and synaptic process and cannot be a memory mechanism. In fact, it is a cellular information storage mechanism.

When discussing the changing sense of reality around 1900 in the cultural arts the lexicon of early modernism reigns supreme. This essay contends that a critical condition for the possibility of many of the turn of the century modernist movements in the arts can be found in exchange of instruments, concepts, and media of representation between the sciences and the arts. One route of interaction came through physiological aesthetics, the attempt to ‘elucidate physiologically the nature of our Aesthetic feelings’ and (...) explain how works of art achieve their effects. Physiological aesthetics provided the terms for new formalist languages of art and criticism, and in some instances suggested optimistic, even utopian, possibilities for art to remake human individuals and societies.Keywords: Physiology; Psychology; Evolution; Aesthetics; Modernism; Art history. (shrink)