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Elaborate force coordination of precision grip could be generalized to bimanual grasping techniques.

Exceptional coordination of grip (G; the normal force that prevents slippage of the grasped object) and load force (L; the tangential force originating from the object's weight and inertia) has been interpreted as a part of evidence that both the anatomy and neural control of human hands have been predominantly designed for manipulation tasks. In the present study, we tested the hypothesis that the precision grasp (uses only the tips of fingers and the thumb of one hand) provides better indices of G and L coordination in static manipulation tasks than two bimanual grasps (palm-palm and fingers-thumb; both using opposing segments of two hands). However, in addition to a subtle difference in relative timing of G and L between the precision and two bimanual grasps, we only found that the fingers-thumb grasp is characterized with higher G/L ratio and somewhat higher modulation of G than not only the precision, but also the bimanual palm-palm grasp. However, all remaining data including the correlation coefficients between G and L demonstrated no difference among three evaluated grasping techniques. Therefore, we concluded that the elaborate G and L coordination associated with uni-manual grasps could be partly generalized to a variety of manipulation tasks including those based on bimanual grasping techniques. Taking into account the importance of manipulation tasks in both everyday life and clinical evaluation, future studies should extend the present research to both other grasping techniques and dynamic manipulation conditions.

Adaptation, Physiological↗

Mitochondrial DNA rates and biogeography in European newts (genus Euproctus).

Sequence divergence for segments of three mitochondrial DNA (mtDNA) genes encoding the 12S and 16S ribosomal RNA and cytochrome b was examined in newts belonging to the genus Euproctus (E. asper, E. montanus, E. platycephalus) and in three other species belonging to the same family (Salamandridae), Triturus carnifex, T. vulgaris, and Pleurodeles waltl. The three Euproctus species occur (one species each) in Corsica, Sardinia, and the Pyrenees. This vicariant distribution is believed to have been determined by the disjunction and rotation of the Sardinia-Corsica microplate from the Pyreneean region. Because time estimates are available for the tectonic events that led to the separation of the three landmasses, we used sequence data to estimate rates of evolution for the three gene fragments and investigated whether they conform to the rate-constancy hypothesis. By the Tajima (1993, Genetics 135:599-607) test, we could not detect rate heterogeneities for the ribosomal genes and for transversions in the cytochrome b gene. Assuming that these sites are evolving linearly over time and that cessation of gene flow occurred simultaneously with vicariant events, we compared the time of divergence estimated by molecular distances with the divergence times based on the geological estimates. Because we have two estimates of divergence time from the geological record, the split of Corsica/Sardinia from the Pyrenees and the split of Corsica from Sardinia, we could compare ratios of molecular divergence with the ratio of geological time divergence. The ratios are very similar, indicating that the molecular clock hypothesis cannot be rejected. These geological events also allowed us to calculate absolute rates of evolution for ribosomal and cytochrome b genes and compare them to rates for the same regions in other salamandrids and other vertebrates. Ribosomal mtDNA rates are comparable to those reported for other vertebrates, but cytochrome b rates are 3-7 times lower in salamanders than in other ectotherms. From a phylogenetic perspective, our data suggest that the cladogenic events leading to species formation in Euproctus and Triturus occurred very closely in time, indicating that the two genera may not be monophyletic. A duplication of the cytochrome b gene in T. carnifex was found, and the implications of this finding for mtDNA phylogenetic studies are discussed.

Animals↗

Dynamic relationship of cycle length to reentrant circuit geometry and to the slow conduction zone during ventricular tachycardia.

BACKGROUND: Knowledge of cycle-to-cycle changes in isthmus geometry is of potential importance for radiofrequency catheter ablation to stop reentrant ventricular tachycardia. It was hypothesized that isthmus geometry often undergoes continuous evolution throughout reentry and that cycle-length variability measurements could be used to segment reentry into distinct phases and to predict changes in isthmus geometry. METHODS AND RESULTS: A canine infarct model of reentrant ventricular tachycardia in the epicardial border zone with a figure 8 pattern of conduction was used for analysis (25 monomorphic reentry episodes, 20 experiments). Tachycardias were segmented, on the basis of cycle-length variations, into 2 to 3 distinct phases corresponding to onset, maintenance, and spontaneous termination, when it occurred (6/25 episodes). Trends of linear cycle-length change occurred throughout the maintenance phase in all tachycardias. For each trend, quantitative geometric parameters of the isthmus were measured, and the following linear relationships were established. During a trend, the slow conduction zone activation interval and tachycardia cycle length increased, while isthmus length decreased. When isthmus length decreased, isthmus width decreased at its narrowed portion. Larger decreases in isthmus length corresponded to higher rates of linear cycle-length prolongation. Also, greater cycle-length variability tended to prolong tachycardia. CONCLUSIONS: Cycle-length alterations occur throughout reentry in this canine model and are predictive of isthmus geometry changes. Because similar reentry dynamics, which affect catheter ablation efficacy, have been observed clinically, estimation of changes in geometry during electrophysiological study may help target ablation sites.

Animals↗

The sleep of long-haul truck drivers.

BACKGROUND: Fatigue and sleep deprivation are important safety issues for long-haul truck drivers. METHODS: We conducted round-the-clock electrophysiologic and performance monitoring of four groups of 20 male truck drivers who were carrying revenue-producing loads. We compared four driving schedules, two in the United States (five 10-hour trips of day driving beginning about the same time each day or of night driving beginning about 2 hours earlier each day) and two in Canada (four 13-hour trips of late-night-to-morning driving beginning at about the same time each evening or of afternoon-to-night driving beginning 1 hour later each day). RESULTS: Drivers averaged 5.18 hours in bed per. day and 4.78 hours of electrophysiologically verified sleep per day over the five-day study (range, 3.83 hours of sleep for those on the steady 13-hour night schedule to 5.38 hours of sleep for those on the steady 10-hour day schedule). These values compared with a mean (+/-SD) self-reported ideal amount of sleep of 7.1+/-1 hours a day. For 35 drivers (44 percent), naps augmented the sleep obtained by an average of 0.45+/-0.31 hour. No crashes or other vehicle mishaps occurred. Two drivers had undiagnosed sleep apnea, as detected by polysomnography. Two other drivers had one episode each of stage 1 sleep while driving, as detected by electroencephalography. Forty-five drivers (56 percent) had at least 1 six-minute interval of drowsiness while driving, as judged by analysis of video recordings of their faces; 1067 of the 1989 six-minute segments (54 percent) showing drowsy drivers involved just eight drivers. CONCLUSIONS: Long-haul truck drivers in this study obtained less sleep than is required for alertness on the job. The greatest vulnerability to sleep or sleep-like states is in the late night and early morning.

Adult↗

Pacemaker potentials in lymphatic smooth muscle of the guinea-pig mesentery.

1. Intracellular microelectrode recordings have been made from lymphatic smooth muscle (SM) to investigate pacemaker mechanisms underlying lymphatic pumping. 2. The SM of small lymphangions or that of short segments, cut from lymphangions of any length, behaved similarly. Both preparations exhibited spontaneous transient depolarizations (STDs) and exhibited simplified electrical characteristics approximating those of a spherical cell. 3. STDs were found to underlie activation of action potentials and hence constrictions. 4. The level of STD activity correlated to the pumping activity of lymphangions, the SM from more active chambers exhibiting increased STD activity. 5. Lymphatic SM exhibited STDs with properties similar to the STDs of mesenteric veins. STDs appeared to be of myogenic origin as they were present despite denervation or substantial destruction of the endothelium. 6. Noradrenaline enhanced the size and frequency of STDs. 7. STD activity was abolished by chelation of cytosolic Ca2+. 8. It is proposed that STDs provide a mechanism for pacemaking in the lymphatic SM studied here. Furthermore, it is postulated that STDs are the consequence of Ca(2+)-dependent pulsatile release of an intracellular messenger, probably Ca2+ itself. This mechanism provides a novel means for pacemaking.

Action Potentials↗

Conduction of hyperpolarization along hamster feed arteries: augmentation by acetylcholine.

The conduction of vasodilation along resistance vessels has been presumed to reflect the electrotonic spread of hyperpolarization from cell to cell along the vessel wall through gap junction channels. However, the vasomotor response to acetylcholine (ACh) encompasses greater distances than can be explained by passive decay. To investigate the underlying mechanism for this behavior, we tested the hypothesis that ACh augments the conduction of hyperpolarization. Feed arteries (n = 23; diameter, 58 +/- 4 microm; segment length, 2-8 mm) were isolated from the hamster retractor muscle, cannulated at each end, and pressurized to 75 mmHg (at 37 degrees C). Vessels were impaled with one or two dye-containing microelectrodes simultaneously (separation distance, 50 microm to 3.5 mm). Membrane potential (E(m)) (rest, approximately -30 mV) and electrical responses were similar between endothelium and smooth muscle, as predicted for robust myoendothelial coupling. Current injection (-0.8 nA, 1.5 s) evoked hyperpolarization (-10 +/- 1 mV; membrane time constant, 240 ms) that conducted along the vessel with a length constant (lambda) = 1.2 +/- 0.1 mm; spontaneous E(m) oscillations (approximately 1 Hz) decayed with lambda = 1.2 + 0.1 mm. In contrast, ACh microiontophoresis (500 nA, 500 ms, 1 microm tip) evoked hyperpolarization (-14 +/- 2 mV) that conducted with lambda = 1.9 +/- 0.1 mm, 60% further (P < 0.05) than responses evoked by purely electrical stimuli. These findings indicate that ACh augments the conduction of hyperpolarization along the vessel wall.

Acetylcholine↗

Phase-dependent effects of spinal cord stimulation on locomotor activity.

This paper examines how electrical stimulation of the spinal cord can modulate the output of the central pattern generator (CPG) for locomotion. Application of discrete current pulses to a single spinal segment was shown to affect multiple parameters of an ongoing locomotor pattern in an in vitro spinal cord. For any given stimulus, the effects on frequency, duration, and symmetry of locomotor output were strongly dependent on the phase at which stimulation was applied within the CPG cycle. Additionally, most stimuli had an immediate impact and evinced no effects on subsequent cycles. The most dramatic changes were seen when stimulation was applied during motor bursting: stimuli applied to the ipsilateral spinal hemicord increased the burst length, while stimuli applied to the contralateral spinal hemicord decreased the burst length. Smaller changes were observed when stimulating during delays between motor bursts. Thus, phasic stimulation was shown to influence the behavior of the CPG and spinal locomotion circuits on a cycle-by-cycle basis. This work represents the first step toward our ultimate goal of developing a neuroprosthetic device to restore locomotion after a severe spinal cord injury.

Action Potentials↗

Neural network simulations of coupled locomotor oscillators in the lamprey spinal cord.

The segmental locomotor network in the lamprey spinal cord was simulated on a computer using a connectionist-type neural network. The cells of the network were identical except for their excitatory levels and their synaptic connections. The synaptic connections used were based on previous experimental work. It was demonstrated that the connectivity of the circuit is capable of generating oscillatory activity with the appropriate phase relations among the cells. Intersegmental coordination was explored by coupling two identical segmental networks using only the cells of the network. Each of the possible couplings of a bilateral pair of cells in one oscillator with a bilateral pair of cells in the other oscillator produced stable phase locking of the two oscillators. The degree of phase difference was dependent upon synaptic weight, and the operating range of synaptic weights varied among the pairs of connections. The coupling was tested using several criteria from experimental work on the lamprey spinal cord. Coupling schemes involving several pairs of connecting cells were found which 1) achieved steady-state phase locking within a single cycle, 2) exhibited constant phase differences over a wide range of cycle periods, and 3) maintained stable phase locking in spite of large differences in the intrinsic frequencies of the two oscillators. It is concluded that the synaptic connectivity plays a large role in producing oscillations in this network and that it is not necessary to postulate a separate set of coordinating neurons between oscillators in order to achieve appropriate phase coupling.

Animals↗

Dopamine replacement therapy does not restore the full spectrum of normal pallidal activity in the 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine primate model of Parkinsonism.

Current physiological studies emphasize the role of neuronal oscillations and synchronization in the pathophysiology of Parkinson's disease; however, little is known about their specific roles in the neuronal substrate of dopamine replacement therapy (DRT). We investigated oscillatory activity and correlations throughout the different states of levodopa-naive parkinsonism as well as "Off-On" and dyskinetic states of DRT in the external globus pallidum (GPe) of tremulous (vervet) and rigid-akinetic (macaque) monkeys and in the internal globus pallidum (GPi) of the vervet monkey. We found that, although oscillatory activity of cells and interneuronal correlation in both pallidal segments increases after induction of parkinsonism with 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) and decreases in response to DRT, important differences exist between the two pallidal segments. In the GPi, the fraction of oscillatory cells and relative power of oscillations were significantly higher than in the GPe, and the dominant frequency was within the range of 7.5-13.5 Hz compared with a range of 4.5-7.5 Hz within the GPe. The interneuronal correlations were mostly oscillatory in the GPi, whereas at least half are non-oscillatory in the GPe. We demonstrate that the tremor characteristics after exposure to DRT do not resemble those of the normal or the levodopa-naive state. Moreover, although DRT reverses the MPTP-induced neuronal changes (rate, pattern, and pairwise correlations), the balance between GPe and GPi fails to restore. We therefore suggest that this imbalance reflects additional abnormal organization of the basal ganglia networks in response to dopamine replacement and may constitute the physiological substrate of the limitations and side effects of chronic DRT.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

A computational model of how an interaction between the thalamocortical and thalamic reticular neurons transforms the low-frequency oscillations of the globus pallidus.

In Parkinson's disease, neurons of the internal segment of the globus pallidus (GPi) display the low-frequency tremor-related oscillations. These oscillatory activities are transmitted to the thalamic relay nuclei. Computer models of the interacting thalamocortical (TC) and thalamic reticular (RE) neurons were used to explore how the TC-RE network processes the low-frequency oscillations of the GPi neurons. The simulation results show that, by an interaction between the TC and RE neurons, the TC-RE network transforms a low-frequency oscillatory activity of the GPi neurons to a higher frequency of oscillatory activity of the TC neurons (the superharmonic frequency transformation). In addition to the interaction between the TC and RE neurons, the low-threshold calcium current in the RE and TC neurons and the hyperpolarization-activated cation current (I (h)) in the TC neurons have significant roles in the superharmonic frequency transformation property of the TC-RE network. The external globus pallidus (GPe) oscillatory activity, which is directly transmitted to the RE nucleus also displays a significant modulatory effect on the superharmonic frequency transformation property of the TC-RE network.

Action Potentials↗

Coordination of cellular pattern-generating circuits that control limb movements: the sources of stable differences in intersegmental phases.

Neuronal mechanisms in nervous systems that keep intersegmental phase lags the same at different frequencies are not well understood. We investigated biophysical mechanisms that permit local pattern-generating circuits in neighboring segments to maintain stable phase differences. We use a modified version of an existing model of the crayfish swimmeret system that is based on three known coordinating neurons and hypothesized intersegmental synaptic connections. Weakly coupled oscillator theory was used to derive coupling functions that predict phase differences between neurons in neighboring segments. We show how features controlling the size of the lag under simplified network configurations combine to create realistic lags in the full network. Using insights from the coupled oscillator theory analysis, we identify an alternative intersegmental connection pattern producing realistic stable phase differences. We show that the persistence of a stable phase lag to changes in frequency can arise from complementary effects on the network with ascending-only or descending-only intersegmental connections. To corroborate the numerical results, we experimentally constructed phase-response curves (PRCs) for two different coordinating interneurons in the swimmeret system by perturbing the firing of individual interneurons at different points in the cycle of swimmeret movement. These curves provide information about the contribution of individual intersegmental connections to the stable phase lag. We also numerically constructed PRCs for individual connections in the model. Similarities between the experimental and numerical PRCs confirm the plausibility of the network configuration that has been proposed and suggest that the same stabilizing balance present in the model underlies the normal phase-constant behavior of the swimmeret system.

Action Potentials↗

Neuronal network models of phase separation between limb CPGs of digging sand crabs.

Ordinary differential equations are used to model a peculiar motor behaviour in the anomuran decapod crustacean Emerita analoga. Little is known about the neural circuitry that permits E. analoga to control the phase relationships between movements of the fourth legs and pair of uropods as it digs into sand, so mathematical models might aid in identifying features of the neural structures involved. The geometric arrangement of segmental ganglia controlling the movements of each limb provides an intuitive framework for modelling. Specifically, due to the rhythmic nature of movement, the network controlling the fourth legs and uropods is viewed as three coupled identical oscillators, one dedicated to the control of each fourth leg and one for the pair of uropods, which always move in bilateral synchrony. Systems of Morris-Lecar equations describe the voltage and ion channel dynamics of neurons. Each central pattern generator for a limb is first modelled as a single neuron and then, more realistically as a multi-neuron oscillator. This process results in high-dimensional systems of equations that are difficult to analyse. In either case, reduction to phase equations by averaging yields a two-dimensional system of equations where variables describe only each oscillator's phase along its limit cycle. The behaviour observed in the reduced equations approximates that of the original system. Results suggest that the phase response function in the two dimensional system, together with minimal input from asymmetric bilateral coupling parameters, is sufficient to account for the observed behaviour.

Action Potentials↗

Nonvisual photoreceptors of the deep brain, pineal organs and retina.

The role of the nonvisual photoreception is to synchronise periodic functions of living organisms to the environmental light periods in order to help survival of various species in different biotopes. In vertebrates, the so-called deep brain (septal and hypothalamic) photoreceptors, the pineal organs (pineal- and parapineal organs, frontal- and parietal eye) and the retina (of the "lateral" eye) are involved in the light-based entrain of endogenous circadian clocks present in various organs. In humans, photoperiodicity was studied in connection with sleep disturbances in shift work, seasonal depression, and in jet-lag of transmeridional travellers. In the present review, experimental and molecular aspects are discussed, focusing on the histological and histochemical basis of the function of nonvisual photoreceptors. We also offer a view about functional changes of these photoreceptors during pre- and postnatal development as well as about its possible evolution. Our scope in some points is different from the generally accepted views on the nonvisual photoreceptive systems. The deep brain photoreceptors are hypothalamic and septal nuclei of the periventricular cerebrospinal fluid (CSF)-contacting neuronal system. Already present in the lancelet and representing the most ancient type of vertebrate nerve cells ("protoneurons"), CSF-contacting neurons are sensory-type cells sitting in the wall of the brain ventricles that send a ciliated dendritic process into the CSF. Various opsins and other members of the phototransduction cascade have been demonstrated in telencephalic and hypothalamic groups of these neurons. In all species examined so far, deep brain photoreceptors play a role in the circadian and circannual regulation of periodic functions. Mainly called pineal "glands" in the last decades, the pineal organs actually represent a differentiated form of encephalic photoreceptors. Supposed to be intra- and extracranially outgrown groups of deep brain photoreceptors, pineal organs also contain neurons and glial elements. Extracranial pineal organs of submammalians are cone-dominated photoreceptors sensitive to different wavelengths of light, while intracranial pineal organs predominantly contain rod-like photoreceptor cells and thus scotopic light receptors. Vitamin B-based light-sensitive cryptochromes localized immunocytochemically in some pineal cells may take part in both the photoreception and the pacemaker function of the pineal organ. In spite of expressing phototransduction cascade molecules and forming outer segment-like cilia in some species, the mammalian pineal is considered by most of the authors as a light-insensitive organ. Expression of phototransduction cascade molecules, predominantly in young animals, is a photoreceptor-like characteristic of pinealocytes in higher vertebrates that may contribute to a light-percepting task in the perinatal entrainment of rhythmic functions. In adult mammals, adrenergic nerves--mediating daily fluctuation of sympathetic activity rather than retinal light information as generally supposed--may sustain circadian periodicity already entrained by light perinatally. Altogether three phases were supposed to exist in pineal entrainment of internal pacemakers: an embryological synchronization by light and in viviparous vertebrates by maternal effects (1); a light-based, postnatal entrainment (2); and in adults, a maintenance of periodicity by daily sympathetic rhythm of the hypothalamus. In addition to its visual function, the lateral eye retina performs a nonvisual task. Nonvisual retinal light perception primarily entrains genetically-determined periodicity, such as rod-cone dominance, EEG rhythms or retinomotor movements. It also influences the suprachiasmatic nucleus, the primary pacemaker of the brain. As neither rods nor cones seem to represent the nonvisual retinal photoreceptors, the presence of additional photoreceptors has been supposed. Cryptochrome 1, a photosensitive molecule identified in retinal nerve cells and in a subpopulation of retinal photoreceptors, is a good candidate for the nonvisual photoreceptor molecule as well as for a member of pacemaker molecules in the retina. When comparing various visual and nonvisual photoreceptors, transitory, "semi visual" (directional) light-perceptive cells can be detected among them, such as those in the parietal eye of reptiles. Measuring diffuse light intensity of the environment, semivisual photoreceptors also possess some directional light perceptive capacity aided by complementary lens-like structures, and screening pigment cells. Semivisual photoreception in aquatic animals may serve for identifying environmental areas of suitable illumination, or in poikilotermic terrestrial species for measuring direct solar irradiation for thermoregulation. As directional photoreceptors were identified among nonvisual light perceptive cells in the lancelet, but eyes are lacking, an early appearance of semivisual function, prior to a visual one (nonvisual --> semivisual --> visual?) in the vertebrate evolution was supposed.

Animals↗

Activity patterns in a model for the subthalamopallidal network of the basal ganglia.

Based on recent experimental data, we have developed a conductance-based computational network model of the subthalamic nucleus and the external segment of the globus pallidus in the indirect pathway of the basal ganglia. Computer simulations and analysis of this model illuminate the roles of the coupling architecture of the network, and associated synaptic conductances, in modulating the activity patterns displayed by this network. Depending on the relationships of these coupling parameters, the network can support three general classes of sustained firing patterns: clustering, propagating waves, and repetitive spiking that may show little regularity or correlation. Each activity pattern can occur continuously or in discrete episodes. We characterize the mechanisms underlying these rhythms, as well as the influence of parameters on details such as spiking frequency and wave speed. These results suggest that the subthalamopallidal circuit is capable both of correlated rhythmic activity and of irregular autonomous patterns of activity that block rhythmicity. Increased striatal input to, and weakened intrapallidal inhibition within, the indirect pathway can switch the behavior of the circuit from irregular to rhythmic. This may be sufficient to explain the emergence of correlated oscillatory activity in the subthalamopallidal circuit after destruction of dopaminergic neurons in Parkinson's disease and in animal models of parkinsonism.

Action Potentials↗

Acute primary angle closure: configuration of the drainage angle in the first year after laser peripheral iridotomy.

PURPOSE: To evaluate the changes in the configuration of the drainage angle in the first year after acute primary angle closure (APAC). DESIGN: Prospective observational case series. PARTICIPANTS: Forty-four Asian subjects with APAC. METHODS: Acute primary angle closure cases were treated with medical therapy followed by laser peripheral iridotomy (LPI). Static and dynamic gonioscopies were performed in APAC-affected and fellow eyes before LPI (baseline) and then at 2 weeks, 4 months, and 12 months after presentation. The angles were graded in each quadrant according to the Shaffer scheme, and the number of clock hours of peripheral anterior synechiae (PAS) was recorded. Patients who underwent intraocular surgery at any point during follow-up were excluded from the study. Intraocular pressure (IOP) and medical treatment were documented at each visit, and gonioscopic changes were correlated with the development of elevation in IOP requiring medical treatment. MAIN OUTCOME MEASURES: Average Shaffer grade and the number of clock hours of PAS. RESULTS: The majority of subjects were Chinese (84%) and female (64%), and the mean age was 60.2+/-10.7 years. At presentation, 73% of both affected and fellow eyes had very narrow angles (average Shaffer grade < or = 1), with affected eyes having more extensive PAS (P<0.001), a third of whom had > or =8 clock hours of PAS. In APAC eyes, there was a significant increase in angle width from baseline to 2 weeks after LPI (P = 0.045), but no change in angle width subsequently. Fellow eyes showed a widening of the angle between baseline and week 2 (P = 0.01) and from week 2 to month 4 (P = 0.001). There was no significant change in PAS in either affected or fellow eyes over the 12 months of follow-up. Of the 44 subjects, 19 (41.3%) subsequently developed IOP elevation during follow-up that required treatment. However, there was no difference in angle width or amount of PAS between eyes with and without a subsequent rise in IOP, and the angle configuration did not change significantly in either group over 1 year. CONCLUSION: In Asian eyes with APAC, the angle widened in the first 2 weeks after LPI, but did not change thereafter over 1 year, and the amount of PAS remained stable throughout. The results indicate the effectiveness of LPI in preventing progressive closure of the angle in the first year after APAC.

Acute Disease↗

Midline serotonergic neurones contribute to widespread synchronized activity in embryonic mouse hindbrain.

Spontaneous, synchronous activity occurs in motor neurones of the embryonic mouse hindbrain at the stage when rhombomeric segmentation disappears (embryonic day 11.5). The mechanisms generating and synchronizing the activity, however, and the extent to which it is widespread in the hindbrain, are unknown. We show here that spontaneous activity is initiated in the midline of the hindbrain, and propagates laterally to encompass virtually the entire hindbrain synchronously and bilaterally. Separation of the midline region from lateral regions abolishes or slows activity laterally, but not medially. The early differentiating neurones of the midline raphe system are present in the rostral midline and express serotonin at E11.5. Their axons ramify extensively in the marginal zone, cross the midline, and extend at the midline both rostrally into the midbrain and caudally towards the caudal hindbrain. Blockers of serotonin receptors, specifically the 5-HT(2A) receptor, abolish synchronous activity in the hindbrain, while blockers of other neurotransmitter systems, including GABA and glutamate, do not. In addition, the 5-HT(2A) receptor is expressed in the marginal regions in the entire medial-to-lateral extent of the hindbrain and in the midline commissural region. Thus, the serotonergic neurones of the developing midline raphe system may play a role in initiating and propagating spontaneous synchronous activity throughout the hindbrain.

Action Potentials↗

Ultrasound biomicroscopy and Scheimpflug photography of angle-supported phakic intraocular lens for high myopia.

PURPOSE: To evaluate the equivalence of Scheimpflug photography (SP) and ultrasound biomicroscopy (UBM) in determining corneal epithelium-intraocular lens (IOL) and border IOL-iris distances. SETTING: Universität Erlangen-Nuremberg, Erlangen, Germany. METHODS: In 26 eyes of 17 patients who had a NuVita MA20 angle-supported anterior chamber intraocular lens (Chiron-Domilens), SP and UBM were used to evaluate the distance between the endothelium and the anterior IOL face in central and peripheral regions (12 o'clock and 6 o'clock positions) and between the border of the anterior IOL face and the iris. The Wilcoxon test was used for statistical analysis. RESULTS: The mean central endothelium-anterior IOL face distance was 2.01 mm and 2.00 mm by SP and UBM, respectively. The mean peripheral endothelium-anterior IOL border distance was 1.28 mm and 1.58 mm, respectively, and the mean peripheral anterior IOL face-iris distance, 0.89 mm and 0.75 mm, respectively. CONCLUSIONS: The difference between the 2 methods in the central endothelium-anterior IOL face distance was not significant (methods were equivalent), but the difference in the peripheral endothelium-anterior IOL face distance was. This may be the result of difficulty in obtaining the exact transition point between the IOL and the haptics by SP examination. The difference between the 2 methods in the IOL border-iris distance was also significant because of the irregularity of the iris surface; therefore, measurements were performed at different sites along this structure. The significant differences in the peripheral endothelium-IOL and IOL border-iris distances indicate that although both methods are useful, they are not equivalent.

Adult↗

[Role of Ca(2+) in the pacemaker-like property of spinal motoneurons].

It is generally accepted that locomotion in vertebrate species is produced by signals coded and integrated by neurons of the spinal cord. In fact, the basic features of locomotion, including patterns and rhythms, are generated by a network of neurons called the CPG (central pattern generator) essentially localized in the lumbar segments of the spinal cord. However, the detailed mechanisms underlying the rhythmic aspect of CPG-generated locomotion are not fully understood. Here, we report data of studies that focus on the role of Ca(2+)-related mechanisms involved in the expression of the pacemaker property of lumbar motoneurons that innervate the hindlimbs. In fact, it has become increasingly clear that Ca(2+) plays a determinant function in the expression of this active and conditional rhythmic property. In addition to NMDA-mediated currents (NMDA is an agonist of the calcium permeable ionotropic glutamatergic receptor) and to a Ca(2+)-dependent K(+) current that were found twenty years ago to contribute to intrinsic voltage oscillations in motoneurons, a pivotal role for voltage-gated channels (e.g., CaV1.3) and intracellular Ca(2+) concentrations ([Ca(2+)]i) have recently been shown. Increasing evidence of a role for metabotropic receptor subtypes, calmodulin (a calcium binding protein), ryanodine and IP3-sensitive intracellular stores of Ca(2+) suggests that additional mechanisms are yet to be identified. A detailed understanding of the complex role of Ca(2+) in mediating the auto-rhythmic property of spinal neurons may contribute to the development of novel therapeutic approaches to induce locomotion after spinal cord injury.

Biological Clocks↗