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High-frequency Stimulation (high-frequency + stimulation)
Selected AbstractsAnatomy and Physiology of the Right Interganglionic Nerve: Implications for the Pathophysiology of Inappropriate Sinus TachycardiaJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2008JING ZHOU M.D. Objective: To simulate inappropriate sinus tachycardia (IST) in experimental animals. Background: We recently found that epinephrine injected into the anterior right ganglionated plexi (ARGP) adjacent to the sinoatrial (SA) node induced an arrhythmia simulating IST. Methods: In 19 anesthetized dogs, via a right thoracotomy, the course of the interganglionic nerve (IGN) from the right stellate ganglion along the superior vena cava to the heart was delineated. High-frequency stimulation (HFS; 0.1 msec duration, 20 Hz, 4.5,9.3 V) was applied to IGN at the junction of innominate vein and SVC. Results: HFS of the IGN significantly increased the sinus rate (SR) (baseline: 156 ± 19 beats/minutes [bpm], 4.5 V: 191 ± 28 bpm*, 8.0 V: 207 ± 23 bpm*, 9.3 V: 216 ± 18 bpm*; *P < 0.01 compared to baseline) without significant changes in A-H interval or blood pressure. P-wave morphology, ice mapping, and noncontact mapping indicated that this tachycardia was sinus tachycardia. In 8 of 19 dogs, injecting hexamethonium (5 mg), a ganglionic blocker, into the ARGP attenuated the response elicited by IGN stimulation (baseline: 160 ± 21 bpm, 4.5 V: 172 ± 32 bpm, 8.0 V: 197 ± 32 bpm*, 9.3 V: 206 ± 26 bpm*; *P < 0.05 compared to baseline). In 19 of 19 animals, after formaldehyde injection into the ARGP, SR acceleration induced by IGN stimulation was markedly attenuated (baseline: 149 ± 17 bpm, 4.5 V: 151 ± 21 bpm, 8.0 V: 155 ± 23 bpm, 9.3 V: 167 ± 24 bpm*; *P < 0.05 compared to baseline). Conclusions: HFS of the IGN caused a selective and significant acceleration of the SR. A significant portion of IGN traverses the ARGP or synapses with the autonomic ganglia in the ARGP before en route to the SA node. Dysautonomia involving the IGN and/or ARGP may play an important role in IST. [source] Influence of the frequency parameter on extracellular glutamate and ,-aminobutyric acid in substantia nigra and globus pallidus during electrical stimulation of subthalamic nucleus in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003François Windels Abstract High-frequency stimulation (HFS) of the subthalamic nucleus (STN) proves to be an efficient treatment for alleviating motor symptoms in Parkinson's disease (PD). However, the mechanisms of HFS underlying these clinical effects remain unknown. Using intracerebral microdialysis, we previously reported that HFS induces, in normal rats, a significant increase of extracellular glutamate (Glu) in the globus pallidus (GP in rats or GPe in primates) and the substantia nigra pars reticulata (SNr), whereas ,-aminobutyric acid (GABA) was increased only in the SNr. Bradykinesia can be improved by STN stimulation in a frequency-dependent manner, a plateau being reached around 130 Hz. The aim of the present study was to determine whether neurochemical changes are also frequency dependent. Electrical STN stimulation was applied at various frequencies (10, 60, 130, and 350 Hz) in normal rats. The results show that, for Glu, the amplitude of increase detected in GP and SNr is maximal at 130 Hz and is maintained at 350 Hz. No modifications of GABA were observed in GP whatever the frequency applied, whereas, in SNr, GABA increased from 60 to 350 Hz. Our results provide new neurochemical data implicating STN target structures in deep-brain-stimulation mechanisms. © 2003 Wiley-Liss, Inc. [source] Dysfunction of the subthalamic nucleus induces behavioral and movement disorders in monkeys,MOVEMENT DISORDERS, Issue 8 2009Carine Karachi MD Abstract High-frequency stimulation of the subthalamic nucleus (STN) in parkinsonian patients is reported to induce psychiatric effects. The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo-functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances. To test this hypothesis, neuronal dysfunction of the STN was induced by microinjections of the GABA agonist muscimol, or antagonist bicucculline, in various parts of the nucleus in three monkeys. Stereotyped behaviors (licking and biting fingers) and/or violent hyperactivity were obtained with bicuculline injected into the anteromedial, associative, and limbic territories, whereas injections of muscimol induced no major effects. Abnormal limb movements (contralateral ballism) were obtained after muscimol or bicuculline injections into the posterolateral, sensorimotor territory. Control injections localized around the STN induced other effects (mainly torticollis), which underlines the specificity of STN injection effects. Our study supports the hypothesis that the anteromedial part of the STN is involved in behavioral control. © 2009 Movement Disorder Society [source] Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: A functional MRI case studyMOVEMENT DISORDERS, Issue 12 2003Taresa Stefurak MD Abstract Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity at the level of the STN and the adjacent white matter tracts (Fields of Forel/zona incerta). © 2003 Movement Disorder Society [source] Excitatory synaptic inputs on myenteric Dogiel type II neurones of the pig ileumTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 2 2001Wim Cornelissen Abstract The synaptic input on myenteric Dogiel type II neurones (n = 63) obtained from the ileum of 17 pigs was studied by intracellular recording. In 77% of the neurones, electrical stimulation of a fibre tract evoked fast excitatory postsynaptic potentials (fEPSPs) with an amplitude of 6 ± 5 mV (mean ± S.D.) and lasting 49 ± 29 ms. The nicotinic nature of the fEPSPs was demonstrated by superfusing hexamethonium (20 ,M). High-frequency stimulation (up to 20 Hz, 3 seconds) did not result in a rundown of the fEPSPs, and did not evoke slow excitatory or inhibitory postsynaptic potentials. The effects of neurotransmitters, possibly involved in these excitatory responses, were investigated. Pressure microejection of acetylcholine (10 mM in pipette) resulted in a fast nicotinic depolarisation in 67%(18/27) of the neurones (13 ± 9 mV, duration 7.0 ± 7.2 seconds) as did 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) application (10 mM; 14 ± 10 mV, duration 4.1 ± 2.8 seconds) in 76%of the cells. The fast nicotinic response to acetylcholine was sometimes (6/27) followed by a slow muscarinic depolarisation (8 ± 4 mV; duration 38.7 ± 10.8 seconds). Immunostaining revealed 5-hydroxytryptamine hydrochloride (5-HT)- and calcitonin gene-related peptide (CGRP)-positive neuronal baskets distributed around and in close vicinity to Dogiel type II neuronal cell bodies. Microejection of 5-HT (10 mM) resulted in a fast nicotinic-like depolarisation (12 ± 6 mV, duration 3.0 ± 1.3 seconds) in 4 of 8 neurones tested, whereas microejection of CGRP (20 mM) gave rise to a slow muscarinic-like depolarisation (6 ± 2 mV, duration 56.0 ± 27.5 seconds) in 8 of 12 neurones tested. In conclusion, myenteric Dogiel type II neurones in the porcine ileum receive diverse synaptic input. Mainly with regard to the prominent presence of nicotinic responses, these neurones behave contrary to their guinea pig counterparts. J. Comp. Neurol. 432:137,154, 2001. © 2001 Wiley-Liss, Inc. [source] Deep brain stimulation mechanisms: beyond the concept of local functional inhibitionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2010Jean-Michel Deniau Abstract Deep brain electrical stimulation has become a recognized therapy in the treatment of a variety of motor disorders and has potentially promising applications in a wide range of neurological diseases including neuropsychiatry. Behavioural observation that electrical high-frequency stimulation of a given brain area induces an effect similar to a lesion suggested a mechanism of functional inhibition. In vitro and in vivo experiments as well as per operative recordings in patients have revealed a variety of effects involving local changes of neuronal excitability as well as widespread effects throughout the connected network resulting from activation of axons, including antidromic activation. Here we review current data regarding the local and network activity changes induced by high-frequency stimulation of the subthalamic nucleus and discuss this in the context of motor restoration in Parkinson's disease. Stressing the important functional consequences of axonal activation in deep brain stimulation mechanisms, we highlight the importance of developing anatomical knowledge concerning the fibre connections of the putative therapeutic targets. [source] Adenosine drives recycled vesicles to a slow-release pool at the mouse neuromuscular junctionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2010Paula P. Perissinotti Abstract The effects of adenosine on neurotransmission have been widely studied by monitoring transmitter release. However, the effects of adenosine on vesicle recycling are still unknown. We used fluorescence microscopy of FM2-10-labeled synaptic vesicles in combination with intracellular recordings to examine whether adenosine regulates vesicle recycling during high-frequency stimulation at mouse neuromuscular junctions. The A1 adenosine receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine) increased the quantal content released during the first endplate potential, suggesting that vesicle exocytosis can be restricted by endogenous adenosine, which accordingly decreases the size of the recycling vesicle pool. Staining protocols designed to label specific vesicle pools that differ in their kinetics of release showed that all vesicles retrieved in the presence of 8-cyclopentyl-1,3-dipropylxanthine were recycled towards the fast-release pool, favoring its loading with FM2-10 and suggesting that endogenous adenosine promotes vesicle recycling towards the slow-release pool. In accordance with this effect, exogenous applied adenosine prevented the replenishment of the fast-release vesicle pool and, thus, hindered its loading with the dye. We had found that, during high-frequency stimulation, Ca2+ influx through L-type channels directs newly formed vesicles to a fast-release pool (Perissinotti et al., 2008). We demonstrated that adenosine did not prevent the effect of the L-type blocker on transmitter release. Therefore, activation of the A1 receptor promotes vesicle recycling towards the slow-release pool without a direct effect on the L-type channel. Further studies are necessary to elucidate the molecular mechanisms involved in the regulation of vesicle recycling by adenosine. [source] L-type calcium channels are involved in fast endocytosis at the mouse neuromuscular junctionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2008Paula P. Perissinotti Abstract We used fluorescence microscopy of FM dyes-labeled synaptic vesicles and electrophysiological recordings to examine the functional characteristics of vesicle recycling and study how different types of voltage-dependent Ca2+ channels (VDCCs) regulate the coupling of exocytosis and endocytosis at mouse neuromuscular junction. Our results demonstrate the presence of at least two different pools of recycling vesicles: a high-probability release pool (i.e. a fast destaining vesicle pool), which is preferentially loaded during the first 5 s (250 action potentials) at 50 Hz; and a low-probability release pool (i.e. a slow destaining vesicle pool), which is loaded during prolonged stimulation and keeps on refilling after end of stimulation. Our results suggest that a fast recycling pool mediates neurotransmitter release when vesicle use is minimal (i.e. during brief high-frequency stimulation), while vesicle mobilization from a reserve pool is the prevailing mechanism when the level of synaptic activity increases. We observed that specific N- and L -type VDCC blockers had no effect on evoked transmitter release upon low-frequency stimulation (5 Hz). However, at high-frequency stimulation (50 Hz), L -type Ca2+ channel blocker increased FM2-10 destaining and at the same time diminished quantal release. Furthermore, when L -type channels were blocked, FM2-10 loading during stimulation was diminished, while the amount of endocytosis after stimulation was increased. Our experiments suggest that L -type VDCCs promote endocytosis of synaptic vesicles, directing the newly formed vesicles to a high-probability release pool where they compete against unused vesicles. [source] CD4+CD25, effector T-cells inhibit hippocampal long-term potentiation in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Gil M. Lewitus Abstract During neuroinflammation T-cells invade the CNS, and may lead to the development and progression of several pathologies, of which multiple sclerosis is the most common. In these pathologies neuroinflammation is often associated with cognitive dysfunction. Using mouse hippocampal slices, we show here that CD4+CD25, T-cells inhibit long-term potentiation (LTP) induced by high-frequency stimulation. The T-cell-mediated inhibition of LTP can be prevented by blockade of ,-aminobutyric acid (GABA)A receptors. These findings provide additional insight into the multiple functions of T-cells in CNS pathologies. [source] Stress reverses plasticity in the pathway projecting from the ventromedial prefrontal cortex to the basolateral amygdalaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2006Mouna Maroun Abstract We have previously shown that high-frequency stimulation to the basolateral amygdala (BLA) induces long-term potentiation (LTP) in the ventromedial prefrontal cortex (vmPFC) and that prior exposure to inescapable stress inhibits the induction of LTP in this pathway [Maroun & Richter-Levin (2003)J. Neurosci., 23, 4406,4409]. Here, we show that the reciprocal pathway projecting from the vmPFC to the BLA is resistant to the induction of LTP. Conversely, long-term depression (LTD) is robustly induced in the BLA in response to low-frequency stimulation to the vmPFC. Furthermore, prior exposure to inescapable stress reverses plasticity in this pathway, resulting in the promotion of LTP and the inhibition of LTD. Our findings suggest that, under normal and safe conditions, the vmPFC is unable to exert excitatory synaptic plasticity over the BLA; rather, LTD, which encodes memory of safety in the BLA, is favoured. Following stressful experiences, LTP in the BLA is promoted to encode memory of fear. [source] Cellular mechanisms of the trigeminally evoked startle responseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2003Susanne Schmid Abstract The startle response is an important mammalian model for studying the cellular mechanisms of emotions and of learning. It consists of contractions of facial and skeletal muscles in response to sudden acoustic, tactile or vestibular stimuli. Whereas the acoustic startle pathway is well described, only a few recent studies have investigated the tactile startle pathway. It was proposed that there is a direct projection from the principal sensory nucleus to the central sensorimotor interface of the startle response, which is formed by the giant neurons in the caudal pontine reticular formation. We explored this projection in greater detail in vitro. Anterograde tracing in rat brain slices confirmed projections with large axon terminals from the ventral part of the principal sensory nucleus to the lateral caudal pontine reticular formation. Electrophysiological studies revealed a monosynaptic glutamatergic connection between principal sensory nucleus neurons and caudal pontine reticular formation giant neurons. The synapses displayed paired-pulse facilitation at high-frequency stimulation, and homosynaptic depression at 1 Hz stimulation. The latter form of plasticity is thought to underlie habituation of the startle response. Furthermore, postsynaptic currents in caudal pontine reticular formation giant neurons evoked by principal sensory nucleus neuron stimulation summed in a linear way with signals evoked by stimulation of auditory afferents. Synaptic plasticity and summation of synaptic currents correspond well with in vivo data previously published by other groups. We thus presume that these synapses mediate trigeminal input to the startle pathway. [source] Transcription factor NF-,B activation after in vivo perforant path LTP in mouse hippocampusHIPPOCAMPUS, Issue 6 2004Ramiro Freudenthal Abstract There is increasing evidence that transcription factors (TFs) play a critical role in maintaining later phases of hippocampal long-term potentiation (LTP). We have been led to study the role in synaptic plasticity of the powerful, yet generally unheralded, NF-,B TF because it may serve as both a signaling molecule after its activation at the synapse and then a transcription initiator upon reaching the nucleus. In the present study, we show that LTP activates NF-,B in the intact mouse hippocampus. Mice were sacrificed 15 min after one of three treatments: tetanization (high-frequency stimulation [HFS]), low-frequency stimulation (LFS), or no stimulated control animals (CT). In a first study, nuclear NF-,B activity from hippocampus was estimated by electrophoretic mobility shift assays (EMSAs). A higher level of hippocampal TF binding to the NF-,B recognition element was found in the HFS group compared with LFS or CT. In a second study, NF-,B activity was evaluated by immunohistochemistry with a specific antibody that recognizes the activated form of NF-,B. This antibody binds to the exposed nuclear location sequence on the p65 subunit of NF-,B consequent to its dissociation from the inhibitory I,B molecule. In the four subfields of hippocampus examined,granule cell layer, hilus of the dentate gyrus, CA3 and CA1 pyramidal fields of the hippocampal gyrus,the highest levels of activated NF-,B, statistically significant in all cases were found after HFS. In certain comparisons, LFS animals also showed significant elevation with respect to CT. These results support the role of NF-,B as part of the synaptic signaling and transcriptional regulation mechanism required in long-term plasticity, emphasizing the combinatorial nature of TF function. © 2004 Wiley-Liss, Inc. [source] Ethanol Attenuates the HFS-Induced, ERK-Mediated LTP in a Dose-Dependent Manner in Rat StriatumALCOHOLISM, Issue 1 2009Gui Qin Xie Background:, The striatum has been implicated to play a role in the control of voluntary behavior, and striatal synaptic plasticity is involved in instrumental learning. Ethanol is known to alter synaptic plasticity, in turn altering the behavior of human and animals. However, it remains unclear whether the striatum plays a role in the effects of ethanol on the central nervous system. The objective of this investigation was to study the effects of acute perfusion of ethanol on long-term potentiation (LTP) to elucidate the mechanisms of addictive drugs in the striatum. In addition, we investigated the contribution of intracellular extracellular signal regulated protein kinase (ERK) signaling pathway to corticostriatal LTP induction. Methods:, The stimulation evoked population spikes (PS) were recorded from the dorsomedial striatum (DMS) slices of rat using the extracellular recording technique. The LTP in DMS slices was induced by high-frequency stimulation (HFS). The ERK level of the DMS was assessed with the Western blot technique. Results:, U0126, the inhibitor of ERK, eliminated or significantly attenuated the LTP induced by HFS of the PS in the DMS. MK801 and APV, N -methyl- d -aspartic acid receptor (NMDAR) antagonists, inhibited the induction of striatal LTP, and HFS-induced ERK activation decreased in the slices treated with MK801 in the DMS. Clinically relevant concentrations of ethanol (22 to 88 mM) dose-dependently attenuated the HFS-induced striatal LTP and ERK activation in this brain region. Conclusions:, The LTP of the PS in the DMS is, at least partly, mediated by the ERK pathway coupling to NMDARs. Ethanol attenuated the HFS-induced, ERK-mediated LTP in a dose-dependent manner in this brain region. These results indicate that ethanol may change the synaptic plasticity of corticostriatal circuits underlying the learning of goal-directed instrumental actions, which is mediated by an intracellular ERK signaling pathway associated with NMDARs. [source] Alterations of Rat Corticostriatal Synaptic Plasticity After Chronic Ethanol Exposure and WithdrawalALCOHOLISM, Issue 5 2006Jian Xun Xia Background: The purpose of this study was to investigate the effects of chronic ethanol exposure (CEE) and withdrawal on corticostriatal plasticity in rats. Methods: We established an animal model of alcoholism using the method of Turchan et al. (1999). A synaptic model of long-term memory (long-term depression, LTD) was used as an index and the striatum, which is related to habit learning, was selected as a target region in the present study. The effects of CEE and withdrawal on the LTD were studied in striatal slices of ethanol-dependent rats using the extracellular recording method. Results: A stable LTD can be induced after high-frequency stimulation (HFS) in the slices of control rats. Chronic ethanol exposure and withdrawal suppressed the induction of corticostriatal LTD to different extents, with the strongest suppressive effects on LTD occurring in the slices of rats exposed to ethanol for 10 days and in those withdrawn from ethanol for 1 day. Notably, 3 days of withdrawal resulted in the shift of corticostriatal synaptic plasticity from LTD to long-term potentiation, and the peak latencies of the population spikes were obviously shortened compared with those of control rats. After 7 days of withdrawal, ethanol's effects tended to disappear. Conclusions: These results suggest that the alterations of corticostriatal synaptic plasticity produced by CEE and withdrawal may play a prominent role in alcohol abuse and alcoholism. [source] Partial lesion of thalamic ventral intermediate nucleus after chronic high-frequency stimulationMOVEMENT DISORDERS, Issue 6 2004Jasmine Henderson PhD Abstract A 73-year-old man with Parkinson's disease underwent thalamic stimulation for disabling tremor with excellent results only when stimulation on. Post-mortem neuropathology (7 years postoperatively) revealed 60% cell loss within 0.5 mm of the electrode tip. Tremor improvement was attributable to chronic stimulation, not microthalamotomy. © 2004 Movement Disorder Society [source] Hypothalamic Deep Brain Stimulation for the Treatment of Chronic Cluster Headaches: A Series ReportNEUROMODULATION, Issue 1 2004Angelo Franzini MD Abstract The objective of this study was to introduce a new surgical treatment for drug-resistant chronic cluster headaches (CH). Because recent functional studies suggested that a hyperactivity of the posterior hypothalamus might be the primary cause of Cluster Headaches (CH) bouts, we designed a prospective study to explore the therapeutic effectiveness of chronic high-frequency stimulation of this region for the treatment of CH. Nine electrodes were stereotactically implanted in the posterior hypothalamus in eight patients suffering from intractable chronic CH. The stereotactic coordinates of the targeted area were 3 mm behind the mid-commissural point, 5 mm below the mid-commissural point, and 2 mm lateral from the midline. Since initiating this treatment in our center, all of the eight patients have improved. Steroid administration has been progressively withdrawn. All of the patients reported that they were pain-free at 1,26 months of follow-up. Three of the eight patients were pain-free without any medication while five of the eight required low doses of methysergide and/or verapamil. No noxious side effects from chronic high-frequency hypothalamic stimulation have been observed nor have we encountered any acute complications from the implant procedure. Tolerance was not observed. We conclude that these preliminary results indicate that hypothalamic stimulation is safe and effective for the treatment of drug-resistant, chronic CH. In addition, these data confirm the "central" pathogenesis for chronic CH. [source] The K+,Cl, cotransporter KCC2 promotes GABAergic excitation in the mature rat hippocampusTHE JOURNAL OF PHYSIOLOGY, Issue 9 2010Tero Viitanen GABAergic excitatory [K+]o transients can be readily evoked in the mature rat hippocampus by intense activation of GABAA receptors (GABAARs). Here we show that these [K+]o responses induced by high-frequency stimulation or GABAA agonist application are generated by the neuronal K+,Cl, cotransporter KCC2 and that the transporter-mediated KCl extrusion is critically dependent on the bicarbonate-driven accumulation of Cl, in pyramidal neurons. The mechanism underlying GABAergic [K+]o transients was studied in CA1 stratum pyramidale using intracellular sharp microelectrodes and extracellular ion-sensitive microelectrodes. The evoked [K+]o transients, as well as the associated afterdischarges, were strongly suppressed by 0.5,1 mm furosemide, a KCl cotransport inhibitor. Importantly, the GABAAR-mediated intrapyramidal accumulation of Cl,, as measured by monitoring the reversal potential of fused IPSPs, was unaffected by the drug. It was further confirmed that the reduction in the [K+]o transients was not due to effects of furosemide on the Na+ -dependent K+ -Cl, cotransporter NKCC1 or on intraneuronal carbonic anhydrase activity. Blocking potassium channels by Ba2+ enhanced [K+]o transients whereas pyramidal cell depolarizations were attenuated in further agreement with a lack of contribution by channel-mediated K+ efflux. The key role of the GABAAR channel-mediated anion fluxes in the generation of the [K+]o transients was examined in experiments where bicarbonate was replaced with formate. This anion substitution had no significant effect on the rate of Cl, accumulation, [K+]o response or afterdischarges. Our findings reveal a novel excitatory mode of action of KCC2 that can have substantial implications for the role of GABAergic transmission during ictal epileptiform activity. [source] Phorbol esters and adenosine affect the readily releasable neurotransmitter pool by different mechanisms at amphibian motor nerve endingsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2003T. J. Searl Phorbol esters and adenosine have been proposed to interact at common sites downstream of calcium entry at amphibian motor nerve endings. We thus studied the actions and interactions of phorbol esters and adenosine using electrophysiological recording techniques in conjunction with both binomial statistical analysis and high-frequency stimulation at the amphibian neuromuscular junction. To begin this study, we confirmed previous observations that synchronous evoked acetylcholine (ACh) release (reflected as endplate potentials, EPPs) is well described by a simple binomial distribution. We then used binomial analysis to study the effects of the phorbol ester phorbol dibutyrate (PDBu, 100 nm) and adenosine (50 µm) on the binomial parameters n (the number of calcium charged ACh quanta available for release) and p (the average probability of release), where the mean level of evoked ACh release (m) =np. We found that PDBu increased m by increasing the parameter n whilst adenosine reduced m by reducing n; neither agent affected the parameter p. PDBu had no effect on either the potency or efficacy of the inhibition produced by adenosine. Subtle differences between these two agents were revealed by the patterns of EPPs evoked by high-frequency trains of stimuli. Phorbol esters increased ACh release during the early phase of stimulation but not during the subsequent plateau phase. The inhibitory effect of adenosine was maximal at the beginning of the train and was still present with reduced efficacy during the plateau phase. When taken together with previous findings, these present results suggest that phorbol esters increase the immediately available store of synaptic vesicles by increasing the number of primed vesicles whilst adenosine acts at a later stage of the secretory process to decrease the number of calcium-charged primed vesicles. [source] Sleep induced by stimulation in the human pedunculopontine nucleus areaANNALS OF NEUROLOGY, Issue 4 2010Isabelle Arnulf MD The pedunculopontine nucleus is part of the reticular ascending arousal system and is involved in locomotion and sleep. Two patients with Parkinson disease received electrodes that stimulated the pedunculopontine nucleus area to alleviate their severe gait impairment. Instead, we found that low-frequency stimulation of the pedunculopontine nucleus area increased alertness, whereas high-frequency stimulation induced non-rapid eye movement sleep. In addition, the sudden withdrawal of the low-frequency stimulation was consistently followed by rapid eye movement sleep episodes in 1 patient. These data have the potential to benefit patients who suffer from sleep disorders. ANN NEUROL 2010;67:546,549 [source] | |||||||||||||