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Use of fractal theory in neuroscience: methods, advantages, and potential problems.

Fractal analysis has already found widespread application in the field of neuroscience and is being used in many other areas. Applications are many and include ion channel kinetics of biological membranes and classification of neurons according to their branching characteristics. In this article we review some practical methods that are now available to allow the determination of the complexity and scaling relationships of anatomical and physiological patterns. The problems of describing fractal dimensions are discussed and the concept of fractal dimensionality is introduced. Several related methodological considerations, such as preparation of the image and estimation of the fractal dimensions from the data points, as well as the advantages and problems of fractal geometric analysis, are discussed.

Algorithms↗

Microarray applications in neuroscience.

Advances in all facets of technology from molecular biology to imaging and computational biology offer unprecedented opportunities for improving our understanding of the brain in health and disease. Oligonucleotide and cDNA microarray analysis, using a variety of "DNA chips," is a recently developed high-throughput technique that allows for tour-de-force analysis of gene expression. We review this powerful technique, developed in genetics laboratories, with reference to applications in neurologic diseases in humans and the use of animal models. The typical microarray experiment is multistaged and includes preparation or purchase of arrays, preparation of target DNA and probe, target DNA hybridization, microarray scanning, and image analysis. The power and pitfalls of this technology are discussed in the context of neuroscience paradigms. Since unprecedented amounts of data are produced from microarray experiments, bioinformatics and modeling expertise are increasingly becoming critical components of this approach.

Animals↗

Cécile & Oskar Vogt: the significance of their contributions in modern neuroscience.

A) By introducing and propagating the use of multidisciplinary approaches, Cécile and Okar Vogt played a decisive role in establishing brain research as a distinct branch of science, and thus laid the foundations for modern Neuroscience. B) The Vogts' and Brodmann's monumental work on brain cytoarchitectonics, supplemented with electrical stimulation of the exposed cerebral cortex, demonstrated correlations between evoked functional responses and the topography of brain regions endowed with distinct cytoarchitectonic structure (topistic units). This opened the field of functional brain mapping, a subject hotly pursued at the present time. C) One of the most important aspects of Pathoclisis is that the Vogts based their theory on molecular genetics. They envisaged that in any topistic unit the neurons had a different specific, molecular ("physico-chemical") composition, accounting for differences observed in the dynamics of neuronal development and involution. In sublethal injury, the induced genomic reactivity varies according to the selective vulnerability of various topistic units. Thus, in cerebral ischemia, the fluctuating genomic reactivity may play a significant role in designing therapeutic strategies, which would include enhancing regenerative expressions and suppressing harmful ones. D) The pathoclisis theory may be of assistance in analyzing the nature of various genetic disorders, which could be considered for the application of gene therapy.

Germany↗

The importance of I.P. Pavlov for the development of neuroscience.

By his experimental and theoretical work on the physiology and pathophysiology of the higher nervous activity I.P. Pavlov significantly influenced the development of Neuroscience. During the 1950 Pavlovian Conference in Moscow, Stalin and the Communist Party tried to dogmatize his and his pupils' fundamental theories. But the Pavlovian ideas were developed by his pupils in open discussions with representatives of other schools in a very creative way, opening the doors for a systemic approach to understanding the integrative functional systems of brain and behavior. Pavlov emphasized the high plasticity of the central nervous system, investigated the complex functional systems within the brain and between the organism and its environment, and designed models for pathological deviations of the higher nervous activity. During his last years, he freed himself from the strong deterministic view and characterized the organism and its environment as a self-organizing system.

History, 19th Century↗

Pavlovian George Windholz (1931-2002): an exemplar of scholarly "observation and observation" and a critical contributor to psychology, and hence to behavioral neuroscience.

Although most members of the Pavlovian Society properly focus their efforts on empirical research, the scholarly, critical conceptual contributions of some individuals are also relevant to progress in psychology and behavioral neuroscience. This paper discusses the contributions of the late George Windholz (often in collaboration with Peter Lamal) as: (a) a historian of Pavlov's life and work; (b) an analyst of priority issues in psychology as a science; (c) a refuter of myths perpetrated by psychology texts. These contributions provide an example of the scholarly form of the motto "observation and observation," where the data used to test hypotheses comprise original documents (often in languages other than English) examined by the historian's critical eye.

Animals↗

[Emotional dysfunction, psychopathy and cognitive neuroscience. What is new and what are the consequences].

This article provides a review of recent findings in the cognitive neurosciences on antisocial personality disorders. There is accumulating evidence that the subtype of psychopathy is characterized by emotional dysfunction not only on the behavioral level but also by structural and functional abnormalities of the brain. Although the findings are not yet conclusive, they are already being discussed controversially with respect to the question of accountability of persons with psychopathy. False conclusions dominating these considerations are discussed and corrected. The findings open a new discussion of the relevance of emotional function and dysfunction for accountability.

Affective Symptoms↗

[Positron emission tomography in neuroscience. An integrative part of clinical diagnostic methods and experimental research].

The role of molecular neuroimaging techniques is increasing in the understanding of pathophysiological mechanism of diseases. To date, positron emission tomography is the most powerful tool for the non-invasive study of biochemical and molecular processes in humans and animals in vivo. With the development in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analyzed by PET. This opens up the exciting and rapidly field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. Besides its usefulness for basic research positron emission tomography has been proven to be superior to conventional diagnostic methods in several clinical indications. This is illustrated by detection of biological or anatomic changes that cannot be demonstrated by computed tomography or magnetic resonance imaging, as well as even before symptoms are expressed. The present review summarizes the clinical use of positron emission tomography in neuroscience that has helped elucidate the pathophysiology of a number of diseases and has suggested strategies in the treatment of these patients. Special reference is given to the neurovascular, neurodegenerative and neurooncological disease.

Animals↗

Recent advances in the application of capillary electrophoresis to neuroscience.

With fast separation times (seconds to minutes), minimal sample requirements (nanoliters to femtoliters), and excellent mass detection limits (femtomole to zeptomole), capillary electrophoresis (CE) is ideally suited for in vitro and in vivo sampling of neurological samples with a high degree of spatial resolution. Advances in extracellular fluid analysis employing improved microdialysis and push-pull perfusion sampling methodologies has enabled the resolution of neurotransmitters present in limited amounts using CE. Great progress has been made to resolve complex neuropeptides, amino acids, and biogenic amines in tissue and cell cultures. Finally, owing largely to the small volume sampling abilities of CE, investigations of single nerve cells, both invertebrate and mammalian, have been accomplished. These applications of CE to the advancement of neuroscience are presented.

Amines↗

PET-based molecular imaging in neuroscience.

Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed.

Alzheimer Disease↗

Trans-NIH neuroscience initiatives on mouse phenotyping and mutagenesis.

In the post-genomic era, the laboratory mouse will excel as a premier mammalian system to study normal and disordered biological processes, in part because of low cost, but largely because of the rich opportunities that exist for exploiting genetic tools and technologies in the mouse to systematically determine mammalian gene function. Many robust models of human disease may therefore be developed, and these in turn will provide critical clues to understanding gene function. The full potential of the mouse for understanding many of the neural and behavioral phenotypes of relevance to neuroscientists has yet to be realized. With the full anatomy of the mouse genome at hand, researchers for the first time will be able to move beyond traditional gene-by-gene approaches and take a global view of gene expression patterns crucial for neurobiological processes. In response to an action plan for mouse genomics developed on the basis of recommendations from the scientific community, seven institutes of the National Institutes of Health (NIH) initiated in 1999 a mouse genetics research program that specifically focused on neurobiology and complex behavior. The specific goals of these neuroscience initiatives are to develop high-throughput phenotyping assays and to initiate genome-wide mutagenesis projects to identify hundreds of mutant strains with heritable abnormalities of high relevance to neuroscientists. Assays and mutants generated in these efforts will be made widely available to the scientific community, and such resources will provide neuroscientists unprecedented opportunities to elucidate the molecular mechanisms of neural function and complex behavior. Such research tools ultimately will permit the manipulation and analysis of the mouse genome, as a means of gaining insight into the genetic bases of the mammalian nervous system and its complex disorders.

Animals↗

Invertebrate studies and their ongoing contributions to neuroscience.

Invertebrates have been deployed very successfully in experimental studies of the nervous system and neuromuscular junctions. Many important discoveries on axonal conduction, synaptic transmission, integrative neurobiology and behaviour have been made by investigations of these remarkable animals. Their advantages as model organisms for investigations of nervous systems include (a) the large diameter of neurons, glia and muscle cells of some invertebrates, thereby facilitating microelectrode recordings; (b) simple nervous systems with few neurons, enhancing the tractability of neuronal circuitry; and (c) well-defined behaviours, which lend themselves to physiological and genetic dissection. Genetic model organisms such as Drosophila melanogaster and Caenorhabditis elegans have provided powerful genetic approaches to central questions concerning nervous system development, learning and memory and the cellular and molecular basis of behaviour. The process of attributing function to particular gene products has been greatly accelerated in recent years with access to entire genome sequences and the application of reverse genetic (e.g. RNA interference, RNAi) and other post-genome technologies (e.g. microarrays). Studies of many other invertebrates, notably the honeybee (Apis mellifera), a nudibranch mollusc (Aplysia californica), locusts, lobsters, crabs, annelids and jellyfish have all assisted in the development of major concepts in neuroscience. The future is equally bright with ease of access to genome-wide reverse genetic technologies, and the development of optical recordings using voltage and intracellular calcium sensors genetically targeted to selected individual and groups of neurons.

Animals↗

RNA interference in neuroscience: progress and challenges.

1.RNA interference (RNAi) is a recently discovered biological pathway that mediates post-transcriptional gene silencing. The process of RNAi is orchestrated by an increasingly well-understood cellular machinery. 2. The common entry point for both natural and engineered RNAi are double stranded RNA molecules known as short interfering RNAs (siRNAs), that mediate the sequence-specific identification and degradation of the targeted messenger RNA (mRNA). The study and manipulation of these siRNAs has recently revolutionized biomedical research. 3. In this review, we first provide a brief overview of the process of RNAi, focusing on its potential role in brain function and involvement in neurological disease. We then describe the methods developed to manipulate RNAi in the laboratory and its applications to neuroscience. Finally, we focus on the potential therapeutic application of RNAi to neurological disease.

Animals↗

Implementing ethics in the professions: preparing guidelines on scientific communication for the Society for Neuroscience. Commentary on 'Implementing ethics in the professions: examples from environmental epidemiology' (Soskolne and Sieswerda).

In 1994, the governing council of the Society for Neuroscience was asked to make a brief statement on an issue regarding responsible conduct in publishing. The present article reviews how that initial request grew over the next four years into a lengthy document. Drawing on that experience, which was presided over by the author, comments are made about the potential impact of such guidelines, the lessons learned, and the proper role of professional societies in promoting responsible conduct in research.

Ethics, Professional↗

Lick sensors as tools in behavioral and neuroscience research.

Lick sensors can be valuable tools in behavioral and neuroscience research on licking and drinking behavior. The focus of this discussion is the recording of licking in the rat. However, comments on the application of these sensors to the measuring of fluid intake are included as well. Lick sensors should be used with adequate precautions. Some constraint on the access of the animal to the drinking tube is necessary for the adequate recording of each single lick. Published drawbacks to the use of electrically operated lick sensors are discussed, and reduced to realistic proportions. With these latter sensors one can obtain behavioral and electrophysiological data that are directly related to the time of making and breaking contact of the tongue with the fluid that is drunk.

Animals↗

Institutional Review Board evaluation of neuroscience protocols involving human subjects.

We analyzed our Institutional Review Board's (IRB) critiques of neuroscience protocols to identify areas of difficulty for investigators. Minutes from IRB meetings were reviewed, and criticisms were collated under applicable Code of Federal Regulations sections, coalescing into four categories: procedural issues, protocol critique, consent critique, and patient rights. Better communication with research subjects would have avoided a majority (66%) of criticisms. Procedural criticisms could have been reduced by adherence to IRB technical requirements. The small number of protocol design criticisms suggests either a lack of rigor in committee analysis or reliance on prior reviewers; it may also reflect the ongoing debate about the role of the IRB in evaluating scientific merit.

Clinical Protocols↗

From basic research to public health policy: WHO report on the neuroscience of substance dependence.

The World Health Organization (WHO) report on the Neuroscience of Psychoactive Substance Use and Dependence represents a summary of the latest scientific knowledge on the role of the brain in substance dependence. The findings of the report have important applications to both interventions and public health policy. Specifically, the report notes that psychoactive substances have physical and symbolic effects that are rewarding to the user. It notes that adverse consequences of psychoactive substance use are related to the level, pattern, mode, and context of use. Dependence is seen as a complex disorder involving brain mechanisms rather than a failure of will. The report notes that psychoactive substance use often coexists with other mental health problems, and that stigma associated with substance misuse inhibits treatment seeking. There is growing evidence for the efficacy and effectiveness of interventions, including advances in pharmacotherapy. However, these advances raise ethical issues that need to be addressed.

Ethics, Clinical↗

Perspectives on the neuroscience of cognition and consciousness.

The origin and current use of the concepts of computation, representation and information in Neuroscience are examined and conceptual flaws are identified which vitiate their usefulness for addressing the problem of the neural basis of Cognition and Consciousness. In contrast, a convergence of views is presented to support the characterization of the Nervous System as a complex dynamical system operating in a metastable regime, and capable of evolving to configurations and transitions in phase space with potential relevance for Cognition and Consciousness.

Cognition↗

Peptide-enhanced cellular internalization of proteins in neuroscience.

Over the last 15 years, many publications described the use of peptide sequences that have been dubbed cell penetrating peptides (CPP), Trojan Horse peptides, protein transduction domains, or membrane-translocating sequences. These mostly positively charged domains bring attached cargo across biological membranes. One of the reasons for the interest in CPP is their potential as delivery tools to enhance the pharmacodynamics of drugs otherwise poorly bioavailable. In particular, the neuroscientist aiming to deliver a protein or other compound into the brain for analytical or therapeutic reasons is faced with the challenge that few drugs cross the blood-brain barrier. CPP are valuable tools to overcome the plasma membrane or the blood-brain barrier in basic research, and in relevant models of neural disease, and will hopefully help to increase the precious few treatments or even cures for people with diseases of the brain and nervous system. Here, we review applications in neuroscience and recent insights into the mechanism of CPP-mediated trafficking.

Animals↗