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PubMed1991

Regulation of hippocampal NMDA receptors by magnesium and glycine during development.

N-Methyl-D-aspartate (NMDA) receptors play an important role in the development of neuronal connections in the retina and visual cortex, and in synaptic plasticity in the hippocampus. The objective of this study was to determine whether the sensitivity of hippocampal NMDA receptors to magnesium, glycine or NMDA changes during development. Xenopus oocytes were injected with mRNA prepared from hippocampi from rats of different ages, and NMDA receptor properties studied under voltage clamp. Voltage-dependent block of the NMDA receptor by magnesium was studied with voltage steps of -90 mV to -30 mV, in increments of 10 mV, during application of 100 microM NMDA, 3 microM glycine and 0-1000 microM Mg2+. The IC50 of Mg2+ for blocking NMDA receptor-mediated currents varied e-fold (2.72-fold) for approximately every 15 mV of membrane potential in the middle range of membrane potential (-70 to -50 mV), but the relationship between log[IC50] for Mg2+ and membrane potential was not linear, as would be expected for simple channel block. The slopes of the curves did not change with development, indicating no change in the voltage-dependence of Mg2+ block with age. However, the IC50 of Mg2+ block did change with age at every membrane potential tested. NMDA receptors expressed from mRNA isolated from 14-15 day old rats were nearly 2-fold less sensitive to block by Mg2+ (IC50 = 33 microM at -60 mV) than those from 1-2 day old rats (IC50 = 18 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

PDZ domain-phosphoinositide interactions in cell-signaling.

Proteins containing PDZ domains function as scaffolds for the formation and spatial confinement of large signaling complexes. They play an important role in the establishment and maintenance of cell polarity and neuronal connectivity. Therefore, they are intensively studied in the context of neurobiology and cancer. It is well established that PDZ domains are protein-interaction modules recognizing short peptide sequences generally situated at the C-terminal end of transmembrane receptors. Yet, it is not clear how those interactions are regulated. Our recent studies revealed that PDZ domains can also interact with phosphoinositides (PIPs), signaling lipids with key-roles in receptor signal transduction, membrane trafficking, cytoskeleton remodeling, subcellular compartmentalization and nuclear processes. In particular, we established that the PDZ domains of syntenin-1 and syntenin-2 bind to phosphatidylinositol 4, 5-bisphosphate (PIP2) with high-affinity. Syntenin-1/PIP2 interaction is important for receptor cargo recycling and syntenin-2 plays a role in the organization of nuclear PIP2. Those study cases indicate that cellular phosphoinositides might function as essential regulators of PDZ proteins. Here, we summarize and discuss our present knowledge about the occurrence, the biochemistry and the functionality of PDZ domain-lipid interactions.

Adaptor Proteins, Signal Transducing↗
PubMed1990

[Development of memory-improving drugs].

Knowledge on the diverse processes involved in memory has been gained from multiple approaches, all necessary for the development of molecules aimed at enhancing memory. However, the neurobiological aspects of apprenticeship and memory remain to be fully elucidated. Long-term storage of information in the nervous system is under the control of glycoprotein synthesis. The chemistry of storage has been extensively studied in mollusks because of their simple neuroarchitecture. In mammals, the phenomenon of hippocampic long-term potentialization (HLTP), to a large extent linked to modification of glutamatergic transmissions, has been demonstrated. Stimulation of N-methyl-DL-aspartase (NMDA) receptors induces an influx of calcium, which is needed for HLTP maintenance, as are the activation of protein kinase C (PKC) and the synthesis of new proteins, for example calmodulin. At the molecular level, a cascade of biochemical events leads to modifications of neuronal connections, thus constituting the basis of memory. Memory-improving substances can be classified according to their theoretical mechanism of action: molecular pharmacology (agents inducing phenomena that mimic HLTP), neurotransmission (molecules acting on the cholinergic, noradrenergic, serotoninergic, GABAergic or dopaminergic systems), pathophysiology (substances antagonizing or correcting anomalies responsible for the memory deficiency, i.e., the cognitive enhancers). The development of memory-enhancing drugs has encountered many obstacles, notably the difficulty in evaluating the effectiveness of a medication in improving memory. It is imperative that guidelines be established for the clinical and experimental development of such substances as well as the standardization of tests in animals and man.

Animals↗
PubMed1989

Transport and targeting of scrapie infectivity and pathology in the optic nerve projections following intraocular infection.

The initial development of scrapie lesions can be seen following intraocular infection to be directly related to sequential infection of connecting neuronal relays within the projections of the optic nerve. For example, intraocular infection of VM mice with 22A virus produces lesions in the contralateral dorsal lateral geniculate nucleus (dLGN) and superior colliculus around halfway through the incubation period of about 360 days; the next lesions appear in the visual cortex, presumably as a result of the transport of infection through the geniculo-cortical tract. Infection of the same strain of mouse with 87V virus produces similar lesions in the dLGN slightly later in the incubation period of about 440 days, although cortical lesions are never seen with this agent. Subsequent lesions with both strains of the virus occur symmetrically in sites which are recognised targets with other routes of infection. Differences of this type provide the opportunity to relate levels of infectivity in sets of neurons directly to subsequent pathological changes. If the two murine Sinc genotypes (Sinc controls incubation period length) are compared after intraocular infection with ME7 virus, the timing of the appearance of the first lesions is in proportion to the length of the incubation period; this may provide a means of identifying the action of Sinc at a cellular level. Serial enucleation following infection of the right eye with ME7 virus has shown that infection takes between 7 and 14 days to reach the superior colliculus and initiate infection via this pathway. This slow rate of spread of infectivity suggests that ME7 is carried in an anterograde direction by the slow rate of axonal transport.

Animals↗
PubMedDate not supplied

[Activity of callosal neurons of the visual cortex in the cat].

Activity of 28 identified neurones of the visual cortex was recorded in cats immobilized by d-tubocurarine. Stimulation of the callosal body with a single stimulus or high-frequency train elicited a short-latency antidromic reaction of neurones in the visual cortex whose axons constitute the main part of the large cerebral commissure. Some commissural neurones responded to a single callosal stimulation by two action potentials the first one being antidromic, the second one being of long-latency postsynaptic origin. The second action potential was generated as a result of activation of axonal collaterals of the same neurone or the neighboring callosal neurones. More than a half of callosal neurones responded to a single stimulation of the lateral geniculate body by short-latency antidromic discharges and by long-latency postsynaptic reactions. These data indicate the existence of the systems of two-way neuronal connections, i.e. calloso-geniculate and geniculo-callosal ones.

Animals↗
PubMed1987

[Serial changes in evoked potentials in kainic acid (KA)-induced limbic seizures in chronic cats].

On the basis of careful histological works including the use of experimental techniques, nearly all of the workers came to the conclusion that no neuronal connections between amygdala and hippocampus exist, regardless of close topographical localization or intimate functional cooperation. We examined ipsilateral amygdalo-hippocampal responses (A-H), hippocampo-amygdaloid responses (H-A) and amygdalo-cortical responses (A-Cx) in normal or epileptic cats by means of evoked potential method. Stereotaxic operations were carried out in ten adult cats. Bipolar electrodes were placed in the left amygdala and ipsilateral dorsal hippocampus, and stainless screws on the dura over the bilateral anterior sigmoid gyrus. A teflon needle with an inner needle guide was also inserted obliquely into the ipsilateral amygdala. The bipolar electrodes allowed both to stimulate and to record the electrical activity. Two hundred rectangular pulses (0.3 msec, 5 V, 2 Hz) were given and evoked responses summed and averaged by a computer. These evoked studies were made before and after KA injection (1 microgram) into the ipsilateral amygdala. In controls, only A-H were observed. During limbic status stage, H-A began to appear and peak latencies of A-H shortened in accordance with seizure development. During generalized seizure stage, A-Cx was newly observed and peak latencies of both A-H and H-A shortened. Peak latencies of the evoked potentials began to shorten soon after development of limbic seizure, and stepwise shortening of peak latencies were recognized in some cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1987

A study on the pattern of alkaline phosphatase activity correlated with observations on silver-impregnated structures in the developing mouse brain.

Alkaline phosphatase activity was localised in specific groups of cellular processes, nuclei and fibre tracts in fetal mouse brain at 9.5-17.5 days post coitum. A radial band of intense enzymatic activity extended longitudinally within the rhombencephalon at 10.5 to 15.5 days. This enzymatic band was topographically related to the efferent nuclei of the cranial nerves, except those nuclei which had migrated laterally to their final positions. The enzymatic activity was seen in some but not all silver-impregnated fibre tracts that appeared early in development, but such association disappeared upon further maturation of the brain. Alkaline phosphatase activity may be related to an enhanced metabolism occurring during the formation of the cranial nerve efferent nuclei and the establishment of neuronal connections in the fetal brain.

Alkaline Phosphatase↗
PubMed1986

A time-comparison circuit in the electric fish midbrain. I. Behavior and physiology.

Behavioral experiments show that the weakly electric fish, Eigenmannia, detects differences in timing as small as 400 nsec between electric signals from different parts of its body surface. The neural basis of this remarkable temporal resolution was investigated by recording from elements of the phase-coding system, a chain of electrotonically connected neurons devoted to the processing of temporal information. Each element of this system fires a single action potential for every cycle of the electric signal (either the fish's own electric organ discharge or a sinusoidal signal of similar frequency). For phase-coding primary afferents and midbrain neurons, the temporal resolution was determined by measuring each unit's capacity to lock its spike to a particular phase of the stimulus cycle. The jitter of a neuron's response (measured as the standard deviation of the timing of the spikes with respect to the stimulus) decreases from the level of the primary afferent (mean = 30 microsec) to the midbrain torus (mean = 11 microsec); these results can be correlated with morphological measures of convergence. The temporal resolution of single neurons is still inferior to that displayed at the behavioral level.

Action Potentials↗
PubMedDate not supplied

Effects of a midsagittal lesion of the rabbit medulla. II. Vagal modulation of respiratory activity.

Vagal reflexes were studied in 12 anaesthetized rabbits after a midsagittal lesion of the medulla oblongata. The rabbits were either breathing spontaneously or were ventilated by a phrenic nerve-controlled servorespirator without the use of muscle relaxants. After splitting the medulla, asynchronous respiratory activity of the left and right phrenic nerves was frequently seen. The vagal reflexes evoked by lung inflation and deflation, cigarette smoke and respiratory loading persisted after the lesion. After unilateral vagotomy, all reflexes were transmitted ipsilaterally to the applied stimulus. On the contralateral side, only reinforcement of inspiration was observed when both phrenic nerves fired in phase. In comparison with the nonlesioned rabbits, vagal input in the split-brainstem preparation has a stronger excitatory effect on inspiratory generation. The existence of self-excitatory neuronal connections in spinal motoneuronal pools is also suggested.

Animals↗
PubMed1983

The persistence of kindled amygdaloid seizures in rats exposed to lindane.

The persistence of the kindled seizure state produced during exposure to 5 mg/kg/day lindane was compared to that produced in nonexposed subjects. Persistence was evaluated at intervals of 2 weeks and 2 months. Rats were kindled on corn oil alone or corn oil + lindane until each rat exhibited a fully kindled seizure. Two weeks later subjects were tested for persistence using a crossover design where half the lindane-kindled rats were retested under lindane and the other half under oil. Two months later, subjects were retested again, without further exposure. The results demonstrate that the kindled state during lindane exposure was equally as stable and persistent as that produced under control conditions. This was true even though kindling required about 40% fewer trials with lindane exposure than without. The equivalence of the control and lindane kindled state is an important finding. It suggests that the proconvulsant action of lindane on kindling is not simply an additive one. Rather, lindane appears to directly increase the rte at which the permanent alterations in neuronal connectivity occur which are responsible for kindling expression.

Amygdala↗
PubMed1981

[Participation of the brain serotoninergic system in creating the stress reactivity of the hypophyseal-adrenal axis].

The concentration of corticosteroids in the blood of rats was shown to increase in response to the immobilization stress at an earlier age than the brain serotonin metabolism changes. The level of corticosteroids in blood increased in response to the intraperitoneal serotonin injection also earlier than the reaction to the serotonin injection in the brain lateral ventricle sets up. The increase of the reaction of hypophysial-suprarenal system to stress during the period from the 12th till the 16th day of postnatal development coincided with the changes in serotonin metabolism in the brain stem and the reaction to serotonin injection in the brain lateral ventricle. It is suggested that the system of serotonin brain neurons connected with the hypophysial-suprarenal complex matures later tran the serotonin receptors in the periphery; the reaction to immobilization may be realized at the early developmental stages without the participation of brain serotonin.

Aging↗
PubMed1980

From reflex to skill: the training of coordination.

All motor activity is based on inherent reflexes and on modification of those reflexes by higher centers. The reflex patterns are developed as the result of the neuronal connections and remain consistent rather than showing variability. It is only the extent of spread of excitation through the entire distribution of the reflex pathway that changes with intensity of stimulation byt the reflex pathway remains constant. Control of reflex activity by the pyramidal system precedes and is the basis for the development of the automatic engrams of coordination. However, precise control can be exerted through the pyramidal system only when the patient is related, the effort is low, and attention is directed to the single activity being attempted. An engram is formed only by repetition of the precise pattern of that engram. In the repetition of a precise pattern the inhibition of muscles which should not be in the pattern is as important as the excitation of the muscles which participate in the pattern. Thousands of repetitions are required to begin to form an engram and millions of repetitions are necessary to perfect it. Coordination is developed in proportion to the number of repetitions of an engram practiced just below the maximal level of ability to perform. The performance of our strongest, fastest, and most complex motor patterns is a function of the extrapyramidal system.

Adult↗
PubMed1995

Simultaneous demonstration of CD15 and alkaline phosphatase activity in cryostat sections of rat fetuses: a detailed technical description for the developing brain.

CD15 and alkaline phosphatase are significant markers of the developing central nervous system. CD15 is known for its interaction in cell-cell contacts, while the presence of alkaline phosphatase is related to the formation of neuronal connections. This paper describes a combined immunocytochemical and enzyme histochemical technique to demonstrate both embryonic markers in the same cryostat section. The monoclonal antibody 3B9, which was used for the detection of CD15 recognizes the immunodominant carbohydrate structure alpha-1,3-Fucosyl-N-Acetyl-Lactosamine also known as X, LewisX, FAL or SSEA-1. This antigen dissolves and is easily rinsed out of the section. The procedure starts off with the detection of CD15. The results of the immunocytochemical procedure is a reaction product which is stable at a high pH, preventing loss of the immunocytochemical reaction product during the subsequent alkaline phosphatase detection. The other embryonic marker, alkaline phosphatase, can only be demonstrated enzymehistochemically if the enzyme is still active. The immunocytochemical localization procedure decided for, does not inactivate alkaline phosphatase totally. From the colorimetrical and histochemical alkaline phosphatase determinations it was concluded that the residual alkaline phosphatase activity detected with this technique, could be intensified by adding Mg(2+)-ions to both the colorimetrical and histochemical incubation media.

Alkaline Phosphatase↗
PubMed1994

Gravitational neuromorphology.

This review shows that morphological studies of the central, peripheral and autonomic nervous system of animals exposed to altered gravity yield data which are extremely significant for our understanding of the mechanisms of adaptation of the nervous system, and of the mammalian organism as a whole, to increased and decreased loading. Neuromorphological studies, correlating structure and function, indicate a decreased activity in weightlessness for spinal ganglia neurons and motoneurons of the spinal cord, as well as the neurons of the hypothalamic nuclei producing arginine vasopressin and growth hormone releasing factor. Structural changes of the somatosensory cortex and spinal ganglia suggest a decreased afferent flow to the somatosensory cortex in microgravity. The results characterize the mechanisms of structural adaptation to a decreased afferent flow in microgravity by the neurons in the hemisphere cortex and brain stem nuclei. There is also morphological evidence for an increased sensitivity of the otolith apparatus and for the development of a hyponoradrenergic syndrome in weightlessness. These studies have shown that both microgravity and the simulation of microgravity effects by tail suspension-induced structural changes in the large neurons of lumbar spinal ganglia and motoneurons of the lumbar spinal cord, which occur under conditions of nerve cell hypoactivity. The structural changes, and consequently the development of neuron hypoactivity, are expressed more extensively after microgravity than after tail suspension for the same length of time. The influence of microgravity and hypergravity on animals is expressed by opposing changes in nervous tissue structure in the spinal ganglia, spinal cord, and nodulus of cerebellar vermis. These changes indicate neuron hypoactivity under microgravity and neuron hyperactivity under 2 G. Morphological assessment of the functional state of other structures of the brain under hypergravity will require further study. Can all structural changes which occur in nerve tissue under microgravity or under hypergravity be explained on the basis of increased or decreased activity of its structural elements? The presently available data regarding the correlation of structure and functional state of cells in brain and spinal cord suggest an affirmative answer. Ultrastructural studies of the nodular cortex of the cerebellum in rats after different duration spaceflights provide what appears to be a convincing example. However, it should be pointed out that the criteria for the morphological assessment of the functional state of single nerve cells will certainly be different from those for groups of neurons connected in a nerve cell network.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Artificial neural networks for predicting failure to survive following in-hospital cardiopulmonary resuscitation.

BACKGROUND: Neural networks are an artificial intelligence technique that uses a set of nonlinear equations to mimic the neuronal connections of biological systems. They have been shown to be useful for pattern recognition and outcome prediction applications, and have the potential to bring artificial intelligence techniques to the personal computers of practicing physicians, assisting them with a variety of medical decisions. It is proposed that such an artificial neural network can be trained, using information available at the time of admission to the hospital, to predict failure to survive following in-hospital cardiopulmonary resuscitation (CPR). METHODS: The age, sex, heart rate, and 21 other clinical variables were collected on a consecutive series of 218 adult patients undergoing CPR at a 295-bed public acute-care hospital. The data set was divided into two groups. A neural network was trained to predict failure to survive to discharge following CPR, using one group as the training set and the other as the testing set. The procedure was then reversed, and the results of the two networks were combined to form an aggregate network. RESULTS: The trained aggregate neural network had a sensitivity of 52.1% and a positive predictive value of 97% for the prediction of failure to survive following CPR. The relative risk of actually failing to survive to discharge following CPR for a patient predicted not to survive was 11.3 (95% CI 3.3 to 38.2). CONCLUSIONS: Predicting failure to survive following CPR is but one possible application of neural network technology. It demonstrates how this technique can assist physicians in medical decision making. Future work should attempt to improve the positive predictive value of the neural network, to consider combining it with an expert system, and to compare it with other predictive tools. Once validated, the network can be distributed as a separate application for use by practicing physicians.

Adolescent↗
PubMed1995

Understanding the functional architecture of cortical tissue in the XIXth century.

This paper outlines the historical development of the idea that the cerebral cortex is responsible for the integration of sensory information and the co-ordination of complex movement patterns. The concept of a functional compartmentalisation of the cortex was developed in the 19th century, based on electrophysiological experiments. In spite of conceptual frameworks like those of Meynert and Wernicke, neuroanatomy did not contribute significantly to the conceptual development of neurobiology during the end of the 19th century. For electrophysiologists, an analysis of neuronal connections in the cortex was of minor interest. Data about the fine texture of the brain did not significantly influence the development of early 20th century neurobiology.

Cerebral Cortex↗
PubMed1996

Joint entropy loci of M and P cells: a hypothesis for parallel processing in the primate visual system.

The M and P neurons connect the retinal inner plexiform layer to the magnicellular and parvicellular layers of the lateral geniculate nucleus and to layer 4 of the primary visual cortex. The M and P pathways transmit visual signals with different six-dimensional joint entropy for space, spatial frequency, time and temporal frequency. Beyond V1 layer 4, M and P influences mix in information processing streams which connect different visual cortical areas. Some visual cortical cells perform better than it is possible for linear filters, regarding to simultaneous spatial and spatial frequency localization of their response. This can be explained by nonlinear combination of M and P input on such cells.

Animals↗
PubMed1998

Brain protein phosphatase 2A: developmental regulation and distinct cellular and subcellular localization by B subunits.

Protein phosphatase 2A (PP2A) is a heterotrimeric enzyme consisting of a catalytic subunit (C), a structural subunit (A), and a variable regulatory subunit (B). We have investigated the spatial and temporal expression patterns of three members of the B subunit family, Balpha, Bbeta, and Bgamma, both at the message level by using ribonuclease protection analysis and at the protein level by using specific antibodies. Although A, Balpha, and C protein are expressed in many tissues, Bbeta and Bgamma were detectable only in brain. Balpha, Bbeta, and Bgamma are components of the brain PP2A heterotrimer, because they copurified with A and C subunits on immobilized microcystin. Whereas Balpha and Bbeta are mainly cytosolic, Bgamma is enriched in the cytoskeletal fraction. In contrast to A, C, and Balpha, which are expressed at constant levels, Bbeta and Bgamma RNA and protein are developmentally regulated, with Bbeta levels decreasing and Bgamma levels increasing sharply after birth. RNA and immunoblot analyses of subdissected brain regions as well as immunohistochemistry demonstrated that B subunits are expressed in distinct but overlapping neuronal populations and cellular domains. These data indicate that B subunits confer tissue and cell specificity, subcellular localization, and developmental regulation to the PP2A holoenzyme. The Balpha-containing heterotrimer may be important in general neuronal functions that involve its partially nuclear localization. Holoenzymes containing B likely function in early brain development as well as in somata and processes of subsets of mature neurons. Bgamma may target PP2A to cytoskeletal substrates that are important in the establishment and maintenance of neuronal connections.

Amino Acid Sequence↗