Changes In Discharge Research Articles

Outflow properties of silos: The effect of arching

Engineers working on the field of agriculture, food- or pharmaceutical industry or in the architecture frequently meet problems arising from the special properties of granular assemblies. Storing large amount of particulate raw materials is mostly made by using large containers, called silos. The design of such large silos is far not an easy problem. The outflow properties are one of the most important parameters of silo design. The constant discharge rate of silos differs from the discharge rate of containers filled with liquids. In case of fluids, the flowing velocity and discharge rate changes with fluid level. In case of granular materials, the velocity is constant (independent of the filling level of silo). There are methods used for the determination of silo discharge rate, but these are mostly experimental without physical explanation of the phenomenon. In this paper we demonstrate that the constant discharge rate is caused by the formation and collapse of arches in the bin. Based on this assumption, we derive an equation for determining the discharge rate. Using the same arching hypothesis we derive the equations describing the velocity distribution at silo outlets. The usability of our new approach is demonstrated by experimental investigations.

Performance Optimization of High Specific Speed Pump-Turbines by Means of Numerical Flow Simulation (CFD) and Model Testing

In recent years, the market has shown increasing interest in pump-turbines. The prompt availability of pumped storage plants and the benefits to the power system achieved by peak lopping, providing reserve capacity, and rapid response in frequency control are providing a growing advantage. In this context, there is a need to develop pumpturbines that can reliably withstand dynamic operation modes, fast changes of discharge rate by adjusting the variable diffuser vanes, as well as fast changes from pumping to turbine operation. In the first part of the present study, various flow patterns linked to operation of a pump-turbine system are discussed. In this context, pump and turbine modes are presented separately and different load cases are shown in each operating mode. In order to create modern, competitive pump-turbine designs, this study further explains what design challenges should be considered in defining the geometry of a pump-turbine impeller. The second part of the paper describes an innovative, staggered approach to impeller development, applied to a low head pump-turbine project. The first level of the process consists of optimization strategies based on evolutionary algorithms together with 3D in-viscid flow analysis. In the next stage, the hydraulic behavior of both pump mode and turbine mode is evaluated by solving the full 3D Navier-Stokes equations in combination with a robust turbulence model. Finally, the progress in hydraulic design is demonstrated by model test results that show a significant improvement in hydraulic performance compared to an existing reference design.

Estimates of EPSP amplitude based on changes in motoneuron discharge rate and probability

When motor units are discharging tonically, transient excitatory synaptic inputs produce an increase in the probability of spike occurrence and also increase the instantaneous discharge rate. Several researchers have proposed that these induced changes in discharge rate and probability can be used to estimate the amplitude of the underlying excitatory post-synaptic potential (EPSP). We tested two different methods of estimating EPSP amplitude by comparing the amplitude of simulated EPSPs with their effects on the discharge of rat hypoglossal motoneurons recorded in an in vitro brainstem slice preparation. The first estimation method (simplified-trajectory method) is based on the assumptions that the membrane potential trajectory between spikes can be approximated by a 10mV post-spike hyperpolarization followed by a linear rise to the next spike and that EPSPs sum linearly with this trajectory. We hypothesized that this estimation method would not be accurate due to interspike variations in membrane conductance and firing threshold that are not included in the model and that an alternative method based on estimating the effective distance to threshold would provide more accurate estimates of EPSP amplitude. This second method (distance-to-threshold method) uses interspike interval statistics to estimate the effective distance to threshold throughout the interspike interval and incorporates this distance-to-threshold trajectory into a threshold-crossing model. We found that the first method systematically overestimated the amplitude of small (<5mV) EPSPs and underestimated the amplitude of large (>5mV EPSPs). For large EPSPs, the degree of underestimation increased with increasing background discharge rate. Estimates based on the second method were more accurate for small EPSPs than those based on the first model, but estimation errors were still large for large EPSPs. These errors were likely due to two factors: (1) the distance to threshold can only be directly estimated over a limited portion of the interspike interval and (2) the distance to threshold can be affected by the EPSP itself. Both methods provide the most accurate EPSP estimates for EPSP amplitudes less than 5mV and moderate background discharge rates (~15imp/s).

Instructed Delay Discharge in Primary and Secondary Somatosensory Cortex Within the Context of a Selective Attention Task

The neuronal mechanisms that contribute to tactile perception were studied using single-unit recordings from the cutaneous hand representation of primate primary (S1) and secondary (S2) somatosensory cortex. This study followed up on our recent observation that S1 and S2 neurons developed a sustained change in discharge during the instruction period of a directed-attention task. We determined the extent to which the symbolic light cues, which signaled the modality (tactile, visual) to attend and discriminate, elicited changes in discharge rate during the instructed delay (ID) period of the attention task and the functional importance of this discharge. ID responses, consisting of a sustained increase or decrease in discharge during the 2-s instruction period, were present in about 40% of the neurons in S1 and S2. ID responses in both cortical regions were very similar in most respects (frequency, sign, latency, amplitude), suggesting a common source. A major difference, however, was related to attentional modulation during the ID period: attentional influences were almost entirely restricted to S2 and these effects were always superimposed on the ID response (additive effect). These findings suggest that the underlying mechanisms for ID discharge and attention are independent. ID discharge significantly modified the initial response to the standard stimuli (competing texture and visual stimuli), usually enhancing responsiveness. We also showed that tactile detection in humans is enhanced during the ID period. Together, the results suggest that ID discharge represents a priming mechanism that prepares cortical areas to receive and process sensory inputs.

Enhanced pronociception by amygdaloid group I metabotropic glutamate receptors in nerve-injured animals

Peripheral neuropathy has been associated with structural and functional changes of the amygdala, a key player in emotions. Here we study whether peripheral neuropathy influences pain regulation by the amygdala. For this purpose, we determined discharge rates of presumably pro- and antinociceptive pain-regulatory neurons in the rostral ventromedial medulla (RVM) following microinjection of various glutamatergic compounds into the central nucleus of the amygdala. RVM neurons were recorded in pentobarbitone-anesthetized rats with a peripheral nerve injury or sham-operation. In a separate behavioral experiment, we determined whether the influence of amygdaloid administration of a glutamatergic compound on affective pain-related behavior, as assessed by an aversive place-conditioning test, is changed by neuropathy. While glutamate or an NMDA receptor antagonist in the amygdala failed to induce marked changes in discharge rates of RVM cells, amygdaloid administration of DHPG, a group I metabotropic glutamate receptor (mGluR) agonist acting on mGluR 1 and mGluR 5, increased discharge rates of presumably pronociceptive RVM ON-cells in nerve-injured but not sham-operated animals. This pronociceptive effect of DHPG was reversed by MPEP (mGluR 5 antagonist) and CPCCOEt (mGluR 1 antagonist). CHPG, an mGluR 5 agonist, failed to influence ON-cell activity and DHPG failed to influence activity of presumably antinociceptive RVM OFF-cells. Amygdaloid administration of DHPG increased and that of CPCCOEt decreased affective pain-related behavior in nerve-injured animals. The results suggest that following nerve injury, the amygdaloid group I mGluR, particularly subtype mGluR 1, has an enhanced pronociceptive effect providing a potential mechanism for emotional enhancement of pain in peripheral neuropathy.

Sympathetic‐induced changes in discharge rate and spike‐triggered average twitch torque of low‐threshold motor units in humans

Animal and in vitro studies have shown that the sympathetic nervous system modulates the contractility of skeletal muscle fibres, which may require adjustments in the motor drive to the muscle in voluntary contractions. In this study, these mechanisms were investigated in the tibialis anterior muscle of humans during sympathetic activation induced by the cold pressor test (CPT; left hand immersed in water at 4 degrees C). In the first experiment, 11 healthy men performed 20 s isometric contractions at 10% of the maximal torque, before, during and after the CPT. In the second experiment, 12 healthy men activated a target motor unit at the minimum stable discharge rate for 5 min in the same conditions as in experiment 1. Intramuscular electromyographic (EMG) signals and torque were recorded and used to assess the motor unit discharge characteristics (experiment 1) and spike-triggered average twitch torque (experiment 2). CPT increased the diastolic blood pressure and heart rate by (mean +/- S.D.) 18 +/- 9 mmHg and 4.7 +/- 6.5 beats min(-1) (P < 0.01), respectively. In experiment 1, motor unit discharge rate increased from 10.4 +/- 1.0 pulses s(-1) before to 11.1 +/- 1.4 pulses s(-1) (P < 0.05) during the CPT. In experiment 2, the twitch half-relaxation time decreased by 15.8 +/- 9.3% (P < 0.05) during the CPT with respect to baseline. These results provide the first evidence of an adrenergic modulation of contractility of muscle fibres in individual motor units in humans, under physiological sympathetic activation.

The effects of experimental muscle and skin pain on the static stretch sensitivity of human muscle spindles in relaxed leg muscles

Animal studies have shown that noxious inputs onto gamma-motoneurons can cause an increase in the activity of muscle spindles, and it has been proposed that this causes a fusimotor-driven increase in muscle stiffness that is believed to underlie many chronic pain syndromes. To test whether experimental pain also acts on the fusimotor system in humans, unitary recordings were made from 19 spindle afferents (12 Ia, 7 II) located in the ankle and toe extensors or peronei muscles of awake human subjects. Muscle pain was induced by bolus intramuscular injection of 0.5 ml 5% hypertonic saline into tibialis anterior (TA); skin pain was induced by 0.2 ml injection into the overlying skin. Changes in fusimotor drive to the muscle spindles were inferred from changes in the mean discharge frequency and discharge variability of spindle endings in relaxed muscle. During muscle pain no afferents increased their discharge activity: seven afferents (5 Ia, 2 II) showed a decrease and six (4 Ia, 2 II) afferents were not affected. During skin pain of 13 afferents discharge rate increased in one (Ia) and decreased in two (1 Ia, 1 II). On average, the overall discharge rate decreased during muscle pain by 6.1% (P < 0.05; Wilcoxon), but remained essentially the same during skin pain. There was no detectable correlation between subjective pain level and the small change in discharge rate of muscle spindles. Irrespective of the type of pain, discharge variability parameters were not influenced (P > 0.05; Wilcoxon). We conclude that, contrary to the 'vicious cycle' hypothesis, acute activation of muscle or skin nociceptors does not cause a reflex increase in fusimotor drive in humans. Rather, our results are more aligned with the pain adaptation model, based on clinical studies predicting pain-induced reductions of agonist muscle activity.

Response properties of electrosensory neurons in the lateral mesencephalic nucleus of the paddlefish

Many fishes and amphibians are able to sense weak electric fields from prey animals or other sources. The response properties of primary afferent fibers innervating the electroreceptors and information processing at the level of the hindbrain is well investigated in a number of taxa. However, there are only a few studies in higher brain areas. We recorded from electrosensory neurons in the lateral mesencephalic nucleus (LMN) and from neurons in the dorsal octavolateral nucleus (DON) of the paddlefish. We stimulated with sine wave stimuli of different amplitudes and frequencies and with moving DC stimuli. During sinusoidal stimulation, DON units increased their firing rate during the negative cycle of the sine wave and decreased their firing rate to the positive cycle. Lateral mesencephalic nucleus units increased their rate for both half cycles of the sine wave. Lateral mesencephalic nucleus units are more sensitive than DON units, especially to small moving dipoles. Dorsal octavolateral nucleus units respond to a moving DC dipole with an increase followed by a decrease in spike rate or vice versa, depending on movement direction and dipole orientation. Lateral mesencephalic nucleus units, in contrast, increased their discharge rate for all stimuli. Any change in discharge rate of DON units is converted in the LMN to a discharge rate increase. Lateral mesencephalic nucleus units therefore appear to code the presence of a stimulus regardless of orientation and motion direction.

Monday July 3, 2006 7:30-9:00 Hall 5B Teaching Session To treat or not to treat the EEG in paediatric epilepsy syndromes

Abstract 1 R. Pressler ( 1 Department of Clinical Neurophysiology, National Hospital for Neurology, UK ) Treatment of interictal discharges can improve behaviour in children with epilepsy Increased behavioural problems in children with epilepsy are a consequence of various factors including underlying brain lesion, age of onset, antiepileptic drugs, psychosocial issues, seizure type and frequency, and interictal EEG abnormalities. Suppression of discharges will improve behaviour in children with nonconvulsive status epilepticus presenting as pseudo-dementia or more subtle behavioural changes, and in children with prolonged nocturnal discharges such as ESES. The effect of intermittent interictal EEG discharges on behaviour and cognition is still controversial. Whether cognitive and behavioural problems can be directly caused by discharges or are a coexisting phenomenon can be determining through improvement of cognition and behaviour, if EEG discharges are suppressed. In children with drug resistant epilepsy and learning difficulties suppression of discharges was associated with improvement in global rating of psychosocial function. In children showing interictal discharges but without epilepsy, suppression of discharges showed no definite effect. In children with well-controlled or mild epilepsy, improved behaviour was only observed in children who showed a reduction of discharges during active treatment, but not in patients without a change in discharge rate. The issue of ‘treating the EEG’ remains controversial. The question is not whether to treat the EEG, but whether seizures, so subtle as to be recognisable only by EEG and behavioural monitoring, produce disability sufficient to justify treatment.

Responses of Monkey Vestibular-Only Neurons to Translation and Angular Rotation

Single-unit recordings were obtained from central vestibular neurons in three monkeys during passive head movements. Neurons that discharged in relation to head translation or changes in head orientation, but not eye movement ("vestibular-only," n = 154), were examined in detail. Neuronal discharge rates were analyzed during four stimulus conditions: sinusoidal head translation in the horizontal plane (0.2-4 Hz, 0.2 g peak acceleration), static head tilt in the vertical plane (+/-20 degrees ), oscillatory head tilt (0.5-2 Hz), and sinusoidal angular rotation about an earth-vertical axis (0.5 or 1 Hz). Vestibular-only cells were divided into two groups based on the regularity of their spontaneous discharge rates (CV*). One group (low-sensitivity units) exhibited regular discharge rates (CV* < 0.2), weak discharge modulation during head translation (<25 spikes . s(-1) . g(-1) at f = 1 Hz), and persistent discharge rates related to static head tilt (0.68 spikes . s(-1) . degrees (-1) of head tilt). The second group (high sensitivity neurons) exhibited irregular discharge rates (CV* > 0.2), strong discharge modulation during head translation ( approximately 100 spikes . s(-1) . g(-1) at f = 1 Hz), and little or no change in discharge rate during static head tilt (0.32 spikes . s(-1) . degrees (-1)). The firing rates of some neurons in both groups were modulated during rotation about an earth-vertical axis (42%), but the modulation was greater for neurons classified as high sensitivity units. Previous reports have described neurons similar to the high sensitivity group; however, the low sensitivity or tilt neurons have not previously been characterized. Significantly, recent theoretical models have predicted neurons with discharge patterns similar to those of low- and high-sensitivity neurons.

Stability of substantia nigra pars reticulata neuronal discharge rates during dopamine receptor blockade and its possible mechanisms

It is hypothesized that substantia nigra pars reticulata neurons become overactive during a deficit of dopamine transmission. In this study, we examined how acute dopamine receptor blockade (SCH23390 and eticlopride) affects impulse activity of substantia nigra pars reticulata neurons and their response to iontophoretic gamma-amino-n-butyric acid in awake, unrestrained rats. No changes in discharge rate were found during complete dopamine receptor blockade, but these neurons showed a diminished response to gamma-amino-n-butyric acid, suggesting gamma-amino-n-butyric acid receptor hyposensitivity. This may result from tonic increase in gamma-amino-n-butyric acid input from the striatum and globus pallidus, which are activated during dopamine receptor blockade. As substantia nigra pars reticulata neurons are autoactive and resistant to tonic increases in gamma-amino-n-butyric acid input, changes in their responsiveness to phasic gamma-amino-n-butyric acid inputs, not tonic increase discharge rate, may underlie movement disturbance following dopamine deficit.

Le cortex cingulaire antérieur dans la détection des erreurs et la gestion des conflits. Analyse de l’activité neuronale chez le singe.

Using a Stroop-like visuo-motor task in monkeys, we studied the unitary neuronal activity of the anterior cingulate cortex (ACC, CMAr : 24c) during error detection and conflict monitoring. A high percentage of cingular neurons modified their firing frequency during both attentional and evaluation periods. During the latter period, however, changes in discharge rates were always much more pronounced for erroneous responses than for successful movements that induced reward delivery. Moreover, some neurons responded more markedly to the warning stimulus when a previous trial failed In this case, the probability of a subsequent correct response increased. Such a neuronal apparatus could represent an error compensation system that serves to adapt a subject's behavioral response following an unfavorable and unexpected outcome. Abnormal activity of these neurons, which appear to take advantage of past errors, could contribute to the genesis of obsessive-compulsive disorders (OCD).

Impact of enforcing the Labour Ordinance, with 1-in-7-day off for hospital doctors, on weekend hospital discharge rate

After enforcing the Labour Ordinance, hospital doctors must have 1 day off-work every week. In this study, we aimed to evaluate its impact on the discharge pattern from an acute medical hospital. We undertook a hospital-based ecologic study with before-after design using the clinical management database of patient discharge records of all acute medical wards in a hospital from January to March 2002 (1 year before new system) and from January to March 2004 (1 year after restricted weekend service). The main outcome measures were the daily discharge rates for the two periods. The odds of being discharged on a Saturday were estimated by multivariate analyses. The number of patient discharge on a Saturday was substantially lower in 2004 as compared to 2002 (47.5 +/- 8.5 per Saturday versus 70.5 +/- 11.1 per Saturday, respectively, p < 0.001). A statistically significant decreased trend was noted in the weekend discharge rate in 2002 and 2004 (Poisson p-value for change in discharge rate, p < 0.001). On the other hand, the number of patient discharges on weekdays did not differ between the two periods. Consistently fewer patients were being discharged on Sundays and Mondays as compared to the rest of the week days in both periods. Compared with study period 2002, patients hospitalized in 2004 (with limited weekend service) had significantly lower multivariate-adjusted odds of being discharged on a Saturday (odds ratio of 0.70; 95 percent confidence interval 0.72-0.89, p < 0.0001). Length of hospital stay is influenced by the health care system delivery apart from clinical factors. Restricted weekend services in an acute medical hospital setting substantially lengthen the hospital stay, and might therefore entail a major financial burden.

Neuronal synchronicity in the pigeon “prefrontal cortex” during learning

In general electrophysiological studies focus on the investigation of changes in discharge rate of neuronal responses which are related to sensory or behavioral events. However, equally important for explanation of higher cognitive functions, learning, memory storage and complex behavior is the interaction between neurons that are connected in cell assemblies. Synchronized inputs onto a neuron are much more effective at eliciting the following activity than uncorrelated inputs. The goal of the present study was to determine either the changes in discharge rate of neurons in the pigeon nidopallium caudolaterale as well as the synchronicity of these neurons during a discriminatory learning task. We found rate modulation effects as well as modulation of synchronization during the learning process.

Controls on conduit magma flow dynamics during lava dome building eruptions

Lava dome eruptions commonly display fairly regular alternations between periods of high and low or no activity with timescales typically of weeks to years and sudden transitions between effusive and explosive activity. We develop a transient model of the magma flow in a volcanic conduit from an open‐system magma chamber with continuous replenishment. The model incorporates gas exsolution, bubble growth, gas escape through the magma, and decompression‐induced crystallization and considers variations in magma temperature, water content, conduit diameter, phenocryst size, chamber volume, and magma rheology. Calculations show the presence of periodic variations in discharge rate due to the transition from a stable regime, when discharge rate is low and crystals grow efficiently leading to high magma viscosity, to another stable state, when discharge rate is high and crystallization is negligible. The difference in discharge rates between these regimes can be several orders of magnitude. Periods are similar to the observed timescales and mainly depend on the chamber volume. The system shows strongly nonlinear responses to the variation of governing parameters. If magma has a Bingham rheology pauses in discharge rate occur between peaks of discharge and the peaks are much higher than for the case of Newtonian rheology. Large changes in discharge rate and eruptive behavior can occur as the consequence of small changes in magma temperature, water content, phenocryst size distribution, or conduit diameter. The system can fluctuate between low and high discharge rates with transitions to explosive activity.

Treatment of interictal epileptiform discharges can improve behavior in children with behavioral problems and epilepsy

It is generally agreed that children should be treated for epilepsy only if they have clinical seizures. The aim of this study was to examine whether suppressing interictal discharges can affect behavior in children with epilepsy. In a double-blinded, placebo-controlled, crossover study, 61 children with well-controlled or mild epilepsy were randomly assigned to add-on therapy with either lamotrigine followed by placebo or placebo followed by lamotrigine. Ambulatory electroencephalographic recordings and behavioral scales were performed during baseline and at the end of placebo and drug phases. The primary hypothesis to be tested was that behavioral scales would improve specifically in patients with a reduction of electroencephalographic discharges during active drug treatment. Global rating of behavior significantly improved only in patients who showed a significant reduction in either frequency ( P < .05) or duration of discharges ( P < .05) during active treatment but not in patients with without a significant change in discharge rate. This improvement was mainly seen in patients with partial epilepsy ( P < .005). Our data suggest that suppressing interictal discharges can improve behavior in children with epilepsy and behavioral problems, particularly partial epilepsy. Focal discharges may be involved in the underlying mechanisms of behavioral problems in epilepsy.

SENSITIVITY OF THIN-WALLED DRIP TAPE EMITTER DISCHARGE TO WATER TEMPERATURE

One of the primary goals in the design of microirrigation systems is to have a hydraulic balance to ensure uniformemitter discharge. However, while most design processes focus on pressure distributions and changes associated with frictionand elevation differences, elevated water temperatures will change the physical properties of the water and may change thephysical properties of some emitters. Laboratory studies were conducted to measure the effects of water operating temperatureon the sensitivity and discharge rate of emitters from thin-walled drip tape (collapsible emitting hose) products. Two differentproduct types (Roberts Ro-Drip, RD; and T-Tape, TT,) each with two wall thicknesses, were evaluated. The RD productincluded wall thicknesses of 0.20 mm (8 mil, RD-08) and 0.38 mm (15 mil, RD-15), whereas the TT product included wallthicknesses of 0.25 mm (10 mil, TT-10) and 0.38 mm (15 mil, TT-15). Additional characterization tests included a standardoperating pressure/emitter discharge rate test and a tubing tensile stress (elongation) test. All tests were conducted inaccordance with ASAE Standard S553, Collapsible Emitting Hose (Drip Tape) Specifications and Performance Testing.Increases in water operating temperature from 21.C to 50.C resulted in an 18%, 44%, and 97% increase in emitter dischargefrom the RD-08 product at operating pressures of 55, 69, and 83 kPa, respectively. Emitter discharge rate changes in theRD-15 product were not as great (10 to 12% increase) for similar water temperature changes. Effects of water temperatureon the discharge rate from the TT products were quite different from the RD products. Emitter discharge rate increasedslightly(<5%) with water temperature at 55 kPa, but decreased by up to 7% at 83 kPa. TDR values (also referred to as atemperature flow rate index) relate the emitter discharge at each measured temperature value (qt.) to the emitter dischargeat the initial base temperature (q20.) [TDR = (qt.)/(q20.)]. In this work, the RD-08 product had a quadratic relationshipbetween temperature discharge ratio and water temperature, while the RD-15 product and both TT-10 and TT-15 productshad more linear relationships.<br><br>Designers of microirrigation systems need the hydraulic performance characteristics of the products that they areconsidering in a system design. Such information should come from the manufacturers of the various collapsible emitting hose(drip tape) products. Product information should clearly provide physical characteristic data such as the emitter exponentx, constant of proportionality k, temperature discharge ratio values, and maximum recommended operatingtemperature.

Training-Related Adaptations in Motor Unit Discharge Rate in Young and Older Adults

This study evaluated changes in motor unit (MU) firing rates in young and older adults during exercise training. Vastus lateralis MU discharge rates were measured in 8 young and 7 older adults. Each participant performed isometric knee extension contractions at 10%, 50%, and 100% of maximal voluntary contraction or effort (MVC) on two separate occasions. Participants then completed a 6-week resistance exercise training protocol. Significant increases in maximal force were observed as early as 1 week after the first baseline testing session, and these were accompanied by increases in the MU discharge rate. Exercise training increased maximal voluntary force by 29% and 36% in the young and older adults, respectively. Motor unit discharge rates at 100% of maximal effort were significantly greater in the young (24.7 pps) than in the older adults (17.8 pps). Furthermore, the young adults also exhibited significantly greater discharge rates at 50% MVC, but there were no differences at the 10% force level. Maximal MU discharge rates increased during the 1-week period separating the two initial testing sessions. After the 6-week training period, maximal MU discharge rates were 15% higher for the young adults and 49% higher for the older adults. No changes in discharge rates were observed for either group at 10% or 50% MVC after exercise training. The early increase in maximal MU discharge rate with repeated maximal force assessment may comprise an important neural mechanism mediating early, rapid gains in muscular force capability.

Subregional changes in discharge rate, pattern, and drug sensitivity of putative GABAergic nigral neurons in the kindling model of epilepsy

The substantia nigra pars reticulata (SNr) is thought to act as a seizure-gating mechanism in kindling and other epilepsy models. We investigated whether the kindling process induces site-specific (anterior-posterior) and seizure-outlasting alterations in the activity of putative GABAergic SNr neurons and in their response to pharmacological manipulation. Female Wistar rats were kindled via the basolateral amygdala by daily stimulation. In vivo extracellular single unit recordings of SNr neurons were performed in kindled rats 1 day after a generalized seizure in order to examine activity changes that outlast the kindled seizures. Sham-kindled and naive rats served as controls. We found a significant and seizure-outlasting increase of discharge rates within the posterior but not within the anterior SNr of kindled rats when compared to controls. Furthermore, kindling resulted in seizure-outlasting burst-like firing pattern of SNr neurons. The antiepileptic drug valproic acid (VPA; 100 mg/kg i.v.) significantly reduced SNr discharge rates in all animal groups. Interestingly, neurons located in the anterior SNr of kindled rats were significantly less depressed by VPA compared to the reduction obtained in naive controls. The present data disclose kindling induced functional plasticity within basal ganglia regions. The findings are relevant for a better understanding of the mechanisms underlying the seizure-gating function of the SNr and might provide new targets for rational therapeutic manipulations, which aim to establish a remote control of epileptic seizures.

Pathophysiology of Parkinson's disease: the MPTP primate model of the human disorder.

The striatum is viewed as the principal input structure of the basal ganglia, while the internal pallidal segment (GPi) and the substantia nigra pars reticulata (SNr) are output structures. Input and output structures are linked via a monosynaptic "direct" pathway and a polysynaptic "indirect" pathway involving the external pallidal segment (GPe) and the subthalamic nucleus (STN). According to current schemes, striatal dopamine (DA) enhances transmission along the direct pathway (via D1 receptors), and reduces transmission over the indirect pathway (via D2 receptors). DA also acts on receptors in GPe, GPi, SNr, and STN. Electrophysiologic and other studies in primates rendered parkinsonian by treatment with the dopaminergic neurotoxin MPTP have demonstrated a reduction of neuronal activity of GPe and an increase of neuronal discharge in STN, GPi. and SNr. These findings are compatible with the view that striatal DA loss results in increased activity over the indirect pathway. Prominent bursting, oscillatory discharge patterns, and increased synchronization of neighboring neurons are found throughout the basal ganglia. These may result from changes in the activity of local circuits (e.g., the GPe-STN "pacemaker") or from more global abnormalities of the basal ganglia-thalamocortical network. These findings have been replicated in human patients undergoing microelectrode-guided stereotactic procedures targeted at GPi or STN. PET studies in patients with Parkinson's disease have lent further support to the proposed circuit abnormalities. The current models of basal ganglia function have recently been criticized. For instance, the strict separation of direct and indirect pathways and the segregation of D1 and D2 receptors have been questioned, and the almost complete absence of motor side effects of pallidal or thalamic lesions in human patients and animals is inconsistent. These results suggest that changes in discharge patterns and synchronization between basal ganglia neurons, abnormal network interactions, and compensatory mechanisms are at least as important in the pathophysiology of parkinsonism as changes in discharge rates in individual basal ganglia nuclei. Lesions of GPi or STN are effective in treating parkinsonism, because they reduce or abolish abnormal basal ganglia output, enabling remaining circuits to function more normally.