Inter-hemispheric competition of sub-cortical structures is a crucial mechanism in paradoxical lesion effects and spatial neglect.
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Attention↗
Biomedical subjects
R Kötter
Publications and source records attributed to R Kötter.
Motor fluctuations in Parkinson's disease: a postsynaptic mechanism derived from a striatal model.
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Corpus Striatum↗
Cellular morphology and physiology of the perinatal rat cerebral cortex.
The cellular morphology and electrophysiology of the rat neocortex between embryonic day (E) 18 and postnatal day (P) 3 was studied in vitro by extracellular biocytin injections and whole-cell recordings, respectively. Most neurons were characterized by a small number of short-range dendrites and a main axon that was directed towards the white matter. Biocytin injections into the marginal zone and the cortical plate labeled far-reaching connections extending up to 2 mm in horizontal direction, indicating the existence of a dense network of long-range intrinsic projections in the neonatal cortex. Action potentials could be elicited as early as E18 and repetitive firing could first be observed at P0. Electrical stimulation of the immature cortex at various positions elicited polyphasic and long-lasting (up to 1 s) excitatory postsynaptic potentials and currents, which were significantly reduced in amplitude by a selective N-methyl-D-aspartate receptor antagonist. Our data indicate that the perinatal cortex manifests the structural and functional conditions for powerful excitatory interactions, which increase the likelihood for the generation of epileptiform activity during this developmental period.
Animals↗
Towards an integration of biochemical and biophysical models of neuronal information processing: a case study in the nigro-striatal system.
The experimental and theoretical study of intracellular biochemical signaling mechanisms lags considerably behind our understanding of electrical processes of neuronal membranes. Both signaling processes, however, are extensively intertwined and can be analyzed and modeled using formally similar mathematical tools. With the nigro-striatal system as an example, we review various formal approaches to describe metabotropic signaling in dopamine- and calcium-dependent pathways and their interactions with electrical membrane processes. These demonstrate the feasibility of synthetic modeling and afford insights into a variety of specific signaling mechanisms. Extending and linking hitherto isolated models has the potential to transcend descriptive levels and to provide a fuller understanding of the molecular basis of macroscopic information processing in the central nervous system.
Animals↗
Trends in European computational neuroscience.
Understanding the complex structure and function of the central nervous system requires the integration of many scientific disciplines and descriptive levels, and the development and application of adequate research tools. The fast growing field of computational neuroscience plays an important role within this integrative effort. In Europe, an active community is emerging that investigates structure-function relationships in the nervous system at subcellular, cellular, network, and behavioural levels. An increasing number of courses and conferences are offering opportunities for development and exchange of ideas between scientists interested in computational neuroscience. Thus, it is timely to present a spectrum of European activities in this field and to foster the communication between scientists across disciplines towards joint efforts.
Computational Biology↗
Species-dependence and relationship of morphological and electrophysiological properties in nigral compacta neurons.
The use of animal models in studying disorders of dopaminergic transmission in humans, such as Parkinson's disease, depends on the assumption that morphological and electrophysiological properties of dopaminergic neurons in the pars compacta of the substantia nigra are relatively constant from rodents to monkeys and humans. While the electrophysiological properties of nigral dopaminergic neurons are highly characteristic and appear to be remarkably uniform, morphological studies of nigral compacta neurons have shown significant size differences across mammalian species. This discrepancy between morphological and electrophysiological characteristics could be reconciled if scaling of neuronal size between species was such that intrinsic properties and responses to afferent inputs would not be affected. We review the principles of morphological scaling of compacta neurons and address this problem by construction and analysis of specific passive and active membrane models. These demonstrate that the size differences between compacta neurons from rats to primates lead to distinct intrinsic electrophysiological properties and that even conservative scaling is not sufficient to ensure constant activity patterns unless further compensatory mechanisms are present. Comparisons with experimental data show that the electrophysiological properties of compacta neurons are characteristic compared to other neuronal types but less uniform than generally recognized. The available data are not sufficient to prove a specific relationship between morphological and electrophysiological properties of compacta neurons but it is evident that they provide no support to the assumption that dopaminergic neurons have similar properties across mammalian species. Thus, comparative experimental studies are required to establish the validity of animal models for nigral function and pathology in humans.
Animals↗
Analysing functional connectivity in brain slices by a combination of infrared video microscopy, flash photolysis of caged compounds and scanning methods.
We evaluate a novel set-up for scanning functional connectivity in brain slices from the somatosensory cortex of the rat. Upright infrared video microscopy for targeted placement of electrodes is combined with rapid photolysis of bath-applied caged neurotransmitter induced by a xenon flash lamp. Flash photolysis of caged glutamate and electrical stimulation produce comparable field potential responses and demonstrate that the viability of the submerged slices exceeds several hours. Glutamate release leads to field potential responses whose two phases are differentially affected by selective blockade of N-methyl-D-aspartate- and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-type glutamate receptors with DL-2-amino-5-phosphonovaleric acid and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulphonamide, respectively. Rapid computer-controlled scanning of hundreds of distinct stimulation sites with simultaneous recordings at a fixed reference site allows construction of functional input maps from peak amplitudes and delays to peak of field potential responses. Selective laminar expansion of the functional input maps after bicuculline application demonstrates that the combination of this conveniently assembled set-up with pharmacological and physical manipulations can provide insights into the determinants of functional connectivity in brain slices.
2-Amino-5-phosphonovalerate↗
Striatal mechanisms in Parkinson's disease: new insights from computer modeling.
We review data and hypotheses concerning the functional anatomy of the striatum and the role of its corticostriatal and nigrostriatal afferents in Parkinson's disease (PD). Starting from molecular mechanisms of glutamatergic and dopaminergic actions in the striatum we have developed a compartmental model of striatal principal neurons that displays a significant degree of biological realism. Simulations of a network of striatal projection neurons under conditions likely to be found in healthy subjects as well as untreated and therapeutic situations of advanced PD provide clues concerning the dynamics of neuronal interactions and their possible effects on downstream motor structures in the generation of positive and negative motor symptoms. We present tentative biological explanations of the symptoms of rigidity and akinesia in PD leading to predictions concerning the origin of abnormal movements and the beneficial effects of dopaminergic treatment. Although these attempts are not yet sufficient to account for the complexity of clinical symptoms found in PD they can guide further empirical research and foster fruitful interactions between experimentalists, theoreticians, and clinicians in unraveling the functional anatomy of the basal ganglia.
Computer Simulation↗
Interactions of glutamate and dopamine in a computational model of the striatum.
A network model of simplified striatal principal neurons with mutual inhibition was used to investigate possible interactions between cortical glutamatergic and nigral dopaminergic afferents in the neostriatum. Glutamatergic and dopaminergic inputs were represented by an excitatory synaptic conductance and a slow membrane potassium conductance, respectively. Neuronal activity in the model was characterized by episodes of increased action potential firing rates of variable duration and frequency. Autocorrelation histograms constructed from the action potential activity of striatal model neurons showed that reducing peak excitatory conductance had the effect of increasing interspike intervals. On the other hand, the maximum value of the dopamine-sensitive potassium conductance was inversely related to the duration of firing episodes and the maximal firing rates. A smaller potassium conductance restored normal firing rates in the most active neurons at the expense of a larger proportion of neurons showing reduced activity. Thus, a homogeneous network with mutual inhibition can produce equally complex dynamics as have been proposed to occur in a striatal network with two neuron populations that are oppositely regulated by dopamine. Even without mutual inhibition it appears that increased dopamine concentrations could partially compensate for the effects of reduced glutamatergic input in individual neurons.
Action Potentials↗
Postsynaptic integration of glutamatergic and dopaminergic signals in the striatum.
The aim of this study was to achieve a better understanding of the integration in striatal medium-sized spiny neurons (MSNs) of converging signals from glutamatergic and dopaminergic afferents. The review of the literature in the first section shows that these two types of afferents not only contact the same striatal cell type, but that individual MSNs receive both a corticostriatal and a dopaminergic terminal. The most common sites of convergence are dendritic shafts and spines of MSNs with a distance between the terminals of less than 1-2 microns. The second section focuses on synaptic transmission and second messenger activation. Glutamate, the candidate transmitter of corticostriatal terminals, via different types of glutamate receptors can evoke an increase in intracellular free calcium concentrations. The net effect of dopamine in the striatum is a stimulation of adenylate cyclase activity leading to an increase in cAMP. The subsequent sections present information on calcium- and cAMP-sensitive biochemical pathways and review the regional and subcellular distribution of the components in the striatum. The specific biochemical reaction steps were formalized as simplified equilibrium equations. Parameter values of the model were chosen from published experimental data. Major results of this analysis are: at intracellular free calcium concentrations below 1 microM the stimulation of adenylate cyclase by calcium and dopamine is at least additive in the steady state. Free calcium concentrations exceeding 1 microM inhibit adenylate cyclase, which is not overcome by dopaminergic stimulation. The kinases and phosphatases studied can be divided in those that are almost exclusively calcium-sensitive (PP2B and CaMPK), and others that are modulated by both calcium and dopamine (PKA and PP1). Maximal threonine-phosphorylation of the phosphoprotein DARPP requires optimal concentrations of calcium (about 0.3 microM) and dopamine (above 5 microM). It seems favourable if the glutamate signal precedes phasic dopamine release by approximately 100 msec. The phosphorylation of MAP2 is under essentially calcium-dependent control of at least five kinases and phosphatases, which differentially affect its heterogeneous phosphorylation sites. Therefore, MAP2 could respond specifically to the spatio-temporal characteristics of different intracellular calcium fluxes. The quantitative description of the calcium- and dopamine-dependent regulation of DARPP and MAP2 provides insights into the crosstalk between glutamatergic and dopaminergic signals in striatal MSNs. Such insights constitute an important step towards a better understanding of the links between biochemical pathways, physiological processes, and behavioural consequences connected with striatal function. The relevance to long-term potentiation, reinforcement learning, and Parkinson's disease is discussed.
Afferent Pathways↗
The limbic system: a review of its empirical foundation.
The concept of the limbic system is highly influential in many areas of the neurosciences and in their applications to clinical medicine. The value of this concept has been questioned, denied, and defended several times in the past but a comprehensive critical evaluation has never been published. In this article we take several approaches to analyse empirical data of relevance to the limbic system. First we delineate its factual application in different areas. The limbic system has a very wide scope and divergent use. Secondly we extract criteria for its definition from research literature using the bibliographic database Medline. The limbic system has been defined variously on a number of different descriptive levels from morphology to behaviour. Thirdly we review its empirical foundations comparing evidence from different sources. The limbic system lacks an adequate empirical definition in spite of numerous efforts. Last we evaluate its construction as a scientific concept from empirical facts. The limbic system is a non-empirical explanatory concept for poorly understood brain functions. We conclude that the concept of the limbic system cannot be accepted on empirical grounds. However, it is a very attractive concept in the search for explanation of brain function. The non-empirical contents of the limbic system remains largely unexplored.
Animals↗
[Fibrous epithelial polyps of the pyelo-ureteral junction in children. Presentation of 3 cases and review of the literature (33 cases)].
Primary ureteral tumors are rare and benign ones constitute only a small portion. Of the benign neoplasms, fibro epithelial polyps are probably the most common and could be considered to be an exceedingly rare cause of Hydronephrosis in children. The exact etiology of benign ureteral polyps is not certain but it is likely that they have a congenital one. They are mesodermal in origin and consist of a thick fibrous stalk covered by a layer of normal transitional epithelium. They are more commonly found in boys (80.6%), who present usually with abdominal pains or renal colics. Fibro-epithelial polyps often rise in the proximal ureter and renal pelvis, especially at the left side (69.4%). Radiographic signs are those of a non typical uretero-pelvic Junction obstruction. IVP and retrograde ureterogram usually demonstrate a long, thin, filiform, lucent filling defect within the ureteral lumen with moderate hydronephrosis. Appropriate treatment of these benign tumors is local excision with or without segmental resection. Prognosis should be considered as excellent without a report of recurrence. A review of the literature revealed 33 cases of ureteral polyps in children. We report here 3 additional cases of obstructing fibro epithelial polyps, observed in boys aged respectively 4, 8 and 9 years.
Child↗
[Phytohaemagglutinin culture as a serial control of lymphoproliferative diseases (author's transl)].
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Adolescent↗
Useless or helpful? The "limbic system" concept.
The "limbic system" is a widespread and frequently used concept in the neurosciences although it is characterized by many different and often vague or even contradictory definitions. This concept has therefore received an increasing amount of critique during the past years. An appraisal of various opinions - ranging from rejection to limited use and support - led us to suggestions concerning its appropriate use. Most importantly, the diversity of definitions and the weak empirical foundation require careful consideration as to what extent certain aspects of the "limbic system" concept can be useful heuristic tools in scientific reasoning.
Animals↗