Intracellular Recording,Sensory Field Mapping,and Culturing Identified Neurons in the Leech,Hirudo medicinalis

The freshwater leech, Hirudo medicinalis, is a versatile model organism that has been used to address scientific questions in the fields of neurophysiology, neuroethology, and developmental biology. The goal of this report is to consolidate experimental techniques from the leech system into a single article that will be of use to physiologists with expertise in other nervous system preparations, or to biology students with little or no electrophysiology experience. We demonstrate how to dissect the leech for recording intracellularly from identified neural circuits in the ganglion. Next we show how individual cells of known function can be removed from the ganglion to be cultured in a Petri dish, and how to record from those neurons in culture. Then we demonstrate how to prepare a patch of innervated skin to be used for mapping sensory or motor fields. These leech preparations are still widely used to address basic electrical properties of neural networks, behavior, synaptogenesis, and development. They are also an appropriate training module for neuroscience or physiology teaching laboratories.     

Incorporating neurophysiological concepts in mathematical thermoregulation models

Skin blood flow (SBF) is a key player in human thermoregulation during mild thermal challenges. Various numerical models of SBF regulation exist. However, none explicitly incorporates the neurophysiology of thermal reception. This study tested a new SBF model that is in line with experimental data on thermal reception and the neurophysiological pathways involved in thermoregulatory SBF control. Additionally, a numerical thermoregulation model was used as a platform to test the function of the neurophysiological SBF model for skin temperature simulation. The prediction-error of the SBF-model was quantified by root-mean-squared-residual (RMSR) between simulations and experimental measurement data. Measurement data consisted of SBF (abdomen, forearm, hand), core and skin temperature recordings of young males during three transient thermal challenges (1 development and 2 validation). Additionally, ThermoSEM, a thermoregulation model, was used to simulate body temperatures using the new neurophysiological SBF-model. The RMSR between simulated and measured mean skin temperature was used to validate the model. The neurophysiological model predicted SBF with an accuracy of RMSR?<?0.27. Tskin simulation results were within 0.37 °C of the measured mean skin temperature. This study shows that (1) thermal reception and neurophysiological pathways involved in thermoregulatory SBF control can be captured in a mathematical model, and (2) human thermoregulation models can be equipped with SBF control functions that are based on neurophysiology without loss of performance. The neurophysiological approach in modelling thermoregulation is favourable over engineering approaches because it is more in line with the underlying physiology.     

The role of the circadian system in fractal neurophysiological control

Many neurophysiological variables such as heart rate, motor activity, and neural activity are known to exhibit intrinsic fractal fluctuations – similar temporal fluctuation patterns at different time scales. These fractal patterns contain information about health, as many pathological conditions are accompanied by their alteration or absence. In physical systems, such fluctuations are characteristic of critical states on the border between randomness and order, frequently arising from nonlinear feedback interactions between mechanisms operating on multiple scales. Thus, the existence of fractal fluctuations in physiology challenges traditional conceptions of health and disease, suggesting that high levels of integrity and adaptability are marked by complex variability, not constancy, and are properties of a neurophysiological network, not individual components. Despite the subject's theoretical and clinical interest, the neurophysiological mechanisms underlying fractal regulation remain largely unknown. The recent discovery that the circadian pacemaker (suprachiasmatic nucleus) plays a crucial role in generating fractal patterns in motor activity and heart rate sheds an entirely new light on both fractal control networks and the function of this master circadian clock, and builds a bridge between the fields of circadian biology and fractal physiology. In this review, we sketch the emerging picture of the developing interdisciplinary field of fractal neurophysiology by examining the circadian system's role in fractal regulation.     

海葵神经毒素研究进展

过去30多年的研究表明,海葵毒液中富含多肽或蛋白类生物毒素活性物质,分子量从3000到80000Da不等。这些毒素可以特异地与某些离子通道或细胞膜受体相结合,从而影响生物的某些生理功能。按照它们功能的不同,可以将海葵毒素大致分为两大类:神经毒素和溶细胞素。由于海葵神经毒素对它们的作用位点具有高度的特异性和亲和性,使得它们成为神经生理学和药理学研究的一种重要工具。就海葵毒素的类型、结构特征、生物活性、应用状况及开发前景的新进展进行综述,以期对同类研究些微启迪。     

Japanese quail (Coturnix japonica) as a laboratory animal model

For the past 50 years, the Japanese quail (Coturnix japonica) has been a popular animal model in numerous fields of research. The quail's 16-d developmental period and its easily accessible embryo make C. japonica a convenient model for studies of developmental biology. Because its lifespan is relatively short and its physiology is comparable to that of humans, the adult quail is useful for studies of aging and disease. The authors describe the Japanese quail as an animal model and, drawing on their experience raising a quail colony at the California Institute of Technology, present detailed guidelines for the husbandry of the species.     

Bibliography of the living coelacanth Latimeria chalumnae,with comments on publication trends

Synopsis A list of published references on the coelacanth Latimeria chalumnae is provided. All known publications in the scientific literature are included as well as popular articles and press reports that are considered to provide new information or interpretations. Marked trends are noticeable in the literature as different disciplines have been applied to research on the coelacanth over the past five decades. The bibliography lists a total of 823 publications including 490 papers in journals, 37 books, 3 theses, 45 chapters in books, 166 popular articles, 22 reports and 60 newspaper articles. Studies on taxonomy and morphology initially dominated the literature followed by reports on research in the fields of physiology, behaviour, breeding biology, ecology and conservation as frozen and eventually live specimens became available for study. The literature on the living coelacanth is predominantly in English, French, Japanese and German but references in 12 other languages were also traced. The dominant authors in the first decades of coelacanth research were the French scientists J. Millot and J. Anthony and the South African describer of the first and second coelacanths, J.L.B. Smith. In subsequent years French, British, American, South African, Japanese, Canadian and German authors, among others, have made significant contributions.     

An analysis of the scientific publications of the A. A. Bogomolets Institute of Physiology of the Academy of Sciences of Ukraine]

Scientific publications from three sectors of the Institute have analyzed for the period since 1979 till 1988 inclusive. The analysis is based on data of annual reference books Science Citation Index (SCI) and lists of publications of each researcher of the Institute. It is shown that with almost equal numerical strength of researchers and similar number of publications the sector of molecular physiology contributed 43.6% to cited works 48.2% of these works are included into database of SCI. Such indices for the sectors of neurophysiology and physiology of visceral systems accounted for 33%, 33.4% and 23.4, 18.4% respectively. It is of interest that 47.5% of references to the cited works of the molecular physiology sector were made by foreign scientists and self-citation constituted 17.4%, while for the other sectors such indices had a reverse relationship. The problem on objectification of estimation of research is under discussion.     

Coming changes in accepted wisdom about "osteoporosis"

Here a voice from the past suggests 28 changes that will affect how people study, manage, classify and think about "osteoporoses" today. Those changes depend mainly on two things: (i) "Connecting the dots" between diverse evidence and ideas from many fields and sources in order to find larger "messages" hidden in mountains of often poorly-organized lesser details, (ii) and features of the still-evolving Utah paradigm of skeletal physiology. That paradigm sums contributions from many people who worked in many fields for over 100 years. In one view it is the most important development in skeletal physiology since Rudolf Virchow and others realized approximately 150 years ago that cells provide the basis for human physiology and diseases. This article emphasizes the above messages instead of the details. The messages affect ideas about the nature, pathogenesis, diagnosis, classification, study and management of osteopenias and osteoporoses, as well as some roles of muscle, drugs, hormones, other agents and fatigue damage, in those disorders. Those larger messages also concern how to classify "osteoporosis fractures", how to define bone health, the choice of absorptiometric methods for noninvasive evaluations of bones, osteopenias and muscle strength, and new criteria for selecting patient cohorts for "risk-of-fracture" analyses and in searches for genetic roles in "osteoporoses". Finally, those larger messages identify many new targets for research that should prove unusually useful in clinical and pharmaceutical domains and work.     

Synaptic Plasticity in Neurodegenerative Diseases Evaluated and Modulated by In Vivo Neurophysiological Techniques

Several studies demonstrated in experimental models and in humans synaptic plasticity impairment in some neurodegenerative and neuropsychiatric diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and schizophrenia. Recently new neurophysiological tools, such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation, have been introduced in experimental and clinical settings for studying physiology of the brain and modulating cortical activity. These techniques use noninvasive transcranial electrical or magnetic stimulation to modulate neurons activity in the human brain. Cortical stimulation might enhance or inhibit the activity of cortico?Csubcortical networks, depending on stimulus frequency and intensity, current polarity, and other stimulation parameters such as the configuration of the induced electric field and stimulation protocols. On this basis, in the last two decades, these techniques have rapidly become valuable tools to investigate physiology of the human brain and have been applied to treat drug-resistant neurological and psychiatric diseases. Here we describe these techniques and discuss the mechanisms that may explain these effects.     

Training Rats to Voluntarily Dive Underwater: Investigations of the Mammalian Diving Response

Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a parasympathetically-induced bradycardia and a sympathetically-induced alteration of vascular resistance that maintains blood flow to the heart, brain and exercising muscles. While many of the metabolic and cardiorespiratory aspects of the diving response have been studied in marine animals, investigations of the central integrative aspects of this brainstem reflex have been relatively lacking. Because the physiology and neuroanatomy of the rat are well characterized, the rat can be used to help ascertain the central pathways of the mammalian diving response. Detailed instructions are provided on how to train rats to swim and voluntarily dive underwater through a 5 m long Plexiglas maze. Considerations regarding tank design and procedure room requirements are also given. The behavioral training is conducted in such a way as to reduce the stressfulness that could otherwise be associated with forced underwater submergence, thus minimizing activation of central stress pathways. The training procedures are not technically difficult, but they can be time-consuming. Since behavioral training of animals can only provide a model to be used with other experimental techniques, examples of how voluntarily diving rats have been used in conjunction with other physiological and neuroanatomical research techniques, and how the basic training procedures may need to be modified to accommodate these techniques, are also provided. These experiments show that voluntarily diving rats exhibit the same cardiorespiratory changes typically seen in other diving animals. The ease with which rats can be trained to voluntarily dive underwater, and the already available data from rats collected in other neurophysiological studies, makes voluntarily diving rats a good behavioral model to be used in studies investigating the central aspects of the mammalian diving response.     

Current concepts in ejaculatory dysfunction

Although erectile dysfunction has recently become the most well-known aspect of male sexual dysfunction, the most prevalent male sexual disorders are ejaculatory dysfunctions. Ejaculatory disorders are divided into 4 categories: premature ejaculation (PE), delayed ejaculation, retrograde ejaculation, and anejaculation/anorgasmia. Pharmacologic treatment for certain ejaculatory disorders exists, for example the off-label use of selective serotonin reuptake inhibitors for PE. Unfortunately, the other ejaculatory disorders are less studied and not as well understood. This review revisits the physiology of the normal ejaculatory response, specifically explores the mechanisms of anejaculation, and presents emerging data. The neurophysiology of the ejaculatory reflex is complex, making classification of the role of individual neurotransmitters extremely difficult. However, recent research has elucidated more about the role of serotonin and dopamine at the central level in the physiology of both arousal and orgasm. Other recent studies that look at differing pharmacokinetic profiles and binding affinities of the alpha(1)-antagonists serve as an indication of the centrally mediated role of ejaculation and orgasm. As our understanding of the interaction between central and peripheral modulations and regulation of the process of ejaculation increases, the probability of developing centrally acting pharmaceutical agents for the treatment of sexual dysfunction approaches reality.     

Using manipulatives to improve learning in the undergraduate neurophysiology curriculum

Educational research has demonstrated that the use of concrete objects or manipulatives in the classroom enhances problem-solving skills and conceptual learning. This project examines the use of manipulatives in a neurophysiology curriculum and assesses their effectiveness on student comprehension. Three activities, building an ion channel, building a nerve cell, and passive membrane properties, were developed using modeling clay and beads as manipulatives. Their effect on learning was assessed in a neurobiology class that had been divided into an experimental group that worked with manipulative-based activities and a control group that did not. After the experimental group had completed the manipulative activity, both groups were given a quiz. Students who had used manipulatives scored significantly better than those who had not. In a second study, students were given a quiz before and after completing a manipulative activity. Students who had used manipulatives showed the greatest grade improvement. These studies suggest that manipulative activities can be used to enhance learning in the neurophysiology curriculum.     

Cell biology, chemogenomics and chemoproteomics

The scientific techniques used in molecular biological research and drug discovery have changed dramatically over the past 10 years due to the influence of genomics, proteomics and bioinformatics. Furthermore, genomics and functional genomics are now merging into a new scientific approach called chemogenomics. Advancements in the study of molecular cell biology are dependent upon "omics" researchers realizing the importance of and using the experimental tools currently available to cell biologists. For example, novel microscopic techniques utilizing advanced computer imaging allow for the examination of live specimens in a fourth dimension, viz., time. Yet, molecular biologists have not taken full advantage of these and other traditional and novel cell biology techniques for the further advancement of genomic and proteomic-oriented research. The application of traditional and novel cellular biological techniques will enhance the science of genomics. The authors hypothesize that a stronger interdisciplinary approach must be taken between cell biology (and its closely related fields) and genomics, proteomics and bio-chemoinformatics. Since there is a lot of confusion regarding many of the "omics" definitions, this article also clarifies some of the basic terminology used in genomics, and related fields. It also reviews the current status and future potential of chemogenomics and its relationship to cell biology. The authors also discuss and expand upon the differences between chemogenomics and the relatively new term--chemoproteomics. We conclude that the advances in cell biology methods and approaches and their adoption by "omics" researchers will allow scientists to maximize our knowledge about life.     

The Relationship Between Psychology and Physiology

A major theoretical problem for Soviety psychophysiologists, many of whom base their work on Pavlovian research and theory, is the integration of Pavlovian doctrine into contemporary knowledge from neurophysiology and the burgeoning theoretical work on cybernetics. Neither modern electrophysiological techniques nor cybernetic ideas were available to Pavlov.     

Prediction of tandem repeat polymorphisms in the coding region of dog genome

After the dog genome was sequenced, an increasing number of studies involving genetic research of dogs have been conducted to understand gene functions and mammalian evolution. To study the genetic diversity in dogs and other mammals, genetic markers linked to function and conserved in wide lineages are necessary. Thus far, few polymorphic markers have been used in dogs. In this study, we surveyed the entire dog genome and predicted a total of 109 tandem repeats (TRs) located on the protein coding region that may be polymorphic by our prediction model. We selected 10 TRs that may be related to neurophysiology and neural developments, and tested them in 167 individuals of 8 dog breeds: 5 European dog breeds (Beagle, Golden Retriever, Labrador Retriever, German Shepherd, and Toy Poodle) and 3 Japanese dog breeds (Japanese Spitz, Shiba, and Shikoku). Among the tested TRs, nine were polymorphic indicating that 90% of the TRs were successfully predicted to be polymorphic. PCR fragments of the TRs were amplified from dog brain cDNA, showing their expression in the dog brain. Our results provide abundant opportunities for the study of phenotypic variations in dogs, and our prediction method for variable number of tandem repeats (VNTRs) can be applied to any other animal genome sequences for the survey of functional and polymorphic markers.     

Neurology,neurosurgery and psychiatry

Neurology, neurosurgery and psychiatry over the past few decades have become more and more segregated in spite of their common foundation in the basic sciences of neuroanatomy, physiology, neurophysiology and neurochemistry. The reasons leading to this unhealthy dichotomy or trichotomy of these specialties dealing with disorders of the nervous system (including behavior) are discussed. Recent advances in the neurobiological sciences are reviewed from the point of view of encouraging and justifying a more healthy integration and working together of these three closely related specialties.     

Genetic Models in Applied Physiology. Functional genomics in the mouse: powerful techniques for unraveling the basis of human development and disease.

Now that near-complete DNA sequences of both the mouse and human genomes are available, the next major challenge will be to determine how each of these genes functions, both alone and in combination with other genes in the genome. The mouse has a long and rich history in biological research, and many consider it a model organism for the study of human development and disease. Over the past few years, exciting progress has been made in developing techniques for chromosome engineering, mutagenesis, mapping and maintenance of mutations, and identification of mutant genes in the mouse. In this mini-review, many of these powerful techniques will be presented along with their application to the study of development, physiology, and disease.     

Future directions for the analysis of musculoskeletal design and locomotor performance

New techniques and conceptual frameworks offer new challenges and exciting opportunities for research on the biomechanics and physiology of vertebrate musculoskeletal design and locomotor performance. Past research based on electromyography and two-dimensional kinematics has greatly advanced the field of vertebrate functional morphology. Studies using these approaches have revealed much about vertebrate structure and function and have emphasized the importance of incorporating historical and developmental constraint and ecological context. Continued use of these experimental tools, but with greater emphasis on three-dimensional analysis of body movement, in combination with 3D kinetics and flow visualization of fluid movement past moving organisms, can now take advantage of the considerable advances in computing power and digital video technology. Indeed, surprisingly few detailed 3D analyses of movement for many locomotor modes and differing organisms are presently available. A challenge of 3D analyses will be to reduce the complexity of the data obtained in order to identify general principles of movement and biomechanics. New techniques and approaches for measuring muscle forces and length changes, together with activation patterns and movement, under dynamic conditions of more varied motor behavior are now also available. These provide the opportunity to study the mechanics and physiology of muscle function at greater depth and under more realistic conditions than has been previously possible. The importance of studying intact, behaving organisms under a broader range of locomotor conditions (other than steady state) and in the context of their natural environment remains a critical need for vertebrate biologists. This provides the much-needed opportunity for placing advances at more cellular and molecular levels into the context of whole organism function. Hence, studies at the organismal level remain paramount.     

The human brain: rewired and running hot

The past two decades have witnessed tremendous advances in noninvasive and postmortem neuroscientific techniques, advances that have made it possible, for the first time, to compare in detail the organization of the human brain to that of other primates. Studies comparing humans to chimpanzees and other great apes reveal that human brain evolution was not merely a matter of enlargement, but involved changes at all levels of organization that have been examined. These include the cellular and laminar organization of cortical areas; the higher order organization of the cortex, as reflected in the expansion of association cortex (in absolute terms, as well as relative to primary areas); the distribution of long-distance cortical connections; and hemispheric asymmetry. Additionally, genetic differences between humans and other primates have proven to be more extensive than previously thought, raising the possibility that human brain evolution involved significant modifications of neurophysiology and cerebral energy metabolism.