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Extracellular Recordings (extracellular + recording)
Selected AbstractsDiamond Transistor Array for Extracellular Recording From Electrogenic CellsADVANCED FUNCTIONAL MATERIALS, Issue 18 2009Markus Dankerl Abstract The transduction of electric signals from cells to electronic devices is mandatory for medical applications such as neuroprostheses and fundamental research on communication in neuronal networks. Here, the use of diamond with its advantages for biological applications as a new material for biohybrid devices for the detection of cell signals is investigated. Using the surface conductivity of hydrogen-terminated single-crystalline diamond substrates, arrays of solution-gate field-effect transistors were fabricated. The characterization of the transistors reveals a good stability in electrolyte solutions for at least 7 days. On these devices, cardiomyocyte-like HL-1 cells as well as human embryonic kidney cells (HEK293), which were stably transfected with potassium channels, are cultured. Both types of cells show healthy growth and good adhesion to the substrate. The diamond transistors are used to detect electrical signals from both types of cells by recording the extracellular potential. For the HL-1 cells, the shape of action potentials can be resolved and the propagation of the signal across the cell layer is visible. Potassium currents of HEK293 cells are activated with the patch-clamp technique in voltage-clamp mode and simultaneously measured with the field-effect transistors. The ion sensitivity of the diamond surface enables the detection of released potassium ions accumulated in the cleft between transistor and cell. [source] Competing Presynaptic and Postsynaptic Effects of Ethanol on Cerebellar Purkinje NeuronsALCOHOLISM, Issue 8 2006Zhen Ming Background: Ethanol has actions on cerebellar Purkinje neurons that can result either in a net excitation or in inhibition of neuronal activity. The present study examines the interplay of presynaptic and postsynaptic mechanisms to determine the net effect of ethanol on the neuronal firing rate of cerebellar Purkinje neurons. Methods: Whole-cell voltage-clamp recording of miniature inhibitory postsynaptic currents (mIPSCs) from Purkinje neurons in cerebellar slices was used to examine the effect of ethanol on presynapticsynaptic release of , -aminobutyric acid (GABA) and glutamate. Extracellular recording was used to examine the net action of both presynaptic and postsynaptic effects of ethanol on the firing rate of Purkinje neurons. Results: Under whole-cell voltage clamp, the frequency of bicuculline-sensitive miniature postsynaptic currents (mIPSCs) was increased dose-dependently by 25, 50, and 100 mM ethanol without any change in amplitude or decay time. Despite this evidence of increased release of GABA by ethanol, application of 50 mM ethanol caused an increase in firing in some neurons and a decrease in firing in others with a nonrandom distribution. When both glutamatergic and GABAergic influences were removed by simultaneous application of 6-cyano-7-nitroquinoxaline-2,3-dione and picrotoxin, respectively, ethanol caused only an increase in firing rate. Conclusions: These data are consistent with a dual action of ethanol on cerebellar Purkinje neuron activity. Specifically, ethanol acts presynaptically to increase inhibition by release of GABA, while simultaneously acting postsynaptically to increase intrinsic excitatory drive. [source] Electrophysiological and behavioural evidence for an antagonistic modulatory role of adenosine A2A receptors in dopamine D2 receptor regulation in the rat dopamine-denervated striatumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2000Ingrid Strömberg Abstract It has been shown that striatal adenosine A2A receptors can antagonistically interact with dopamine D2 receptors at the membrane level leading to a decrease in the affinity and efficacy of D2 receptors. Extracellular recordings and rotational behaviour were employed to obtain a correlate to these findings in an animal model of Parkinson's disease (PD). The recordings were performed in rats with unilateral 6-hydroxydopamine (6-OHDA)-induced catecholamine depletion. While recording in the dopamine-depleted striatum, local applications of the dopamine D2 agonist quinpirole reduced neuronal activity. However, when the adenosine A2A antagonist MSX-3 was applied simultaneously with quinpirole, the inhibition of neuronal firing seen after quinpirole alone was significantly potentiated (P < 0.001, n = 11). In contrast, local application of CGS 21680 attenuated the effect of quinpirole. The doses of MSX-3 and CGS 21680 used to achieve the modulation of quinpirole action had no effect per se on striatal neuronal firing. Furthermore, rotational behaviour revealed that MSX-3 dose-dependently increased the number of turns when administrated together with a threshold dose of quinpirole while no enhancement was achieved when MSX-3 was combined with SKF 38393. MSX-3 alone did not induce rotational behaviour. In conclusion, this study shows that low ineffective doses of MSX-3 enhance the effect of quinpirole on striatal firing rate, while the A2A agonist exerts the opposite action. This mechanism gives a therapeutic potential to A2A antagonists in the treatment of PD by enhancing D2 receptor function. [source] Nicotine reverses adult-onset hypothyroidism-induced impairment of learning and memory: Behavioral and electrophysiological studiesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2006K.H. Alzoubi Abstract Nicotine alleviates cognitive impairment associated with a variety of health conditions. We examined the effect of chronic nicotine treatment on adult-onset hypothyroidism-induced impairment of learning and memory in rats. Hypothyroidism was induced by surgical removal of thyroid glands (thyroidectomy). One month later, chronic nicotine treatment (1 mg/kg sc, twice/day) was instituted for 4,6 weeks. Test of hippocampus-dependent spatial learning and memory in the radial arm water maze showed that hypothyroidism impaired learning as well as short-term and long-term memory retention. Chronic nicotine treatment reversed the hypothyroidism-induced learning and memory impairment. In normal rats, chronic nicotine treatment had no effect on learning and memory. Extracellular recordings from the CA1 region of anesthetized hypothyroid rats showed severe reduction of both early-phase and late-phase long-term potentiation (LTP) magnitude, which was reversed in nicotine-treated hypothyroid rats. These results show that chronic nicotine treatment prevents hypothyroidism-induced impairment of spatial cognition and LTP. © 2006 Wiley-Liss, Inc. [source] 5-Hydroxytryptamine selectively activates the vagal nodose C-fibre subtype in the guinea-pig oesophagusNEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2008S. Yu Abstract, The afferent neurons innervating the oesophagus originate from two embryonic sources: neurons located in vagal nodose ganglia originate from embryonic placodes and neurons located in vagal jugular and spinal dorsal root ganglia (DRG) originate from the neural crest. Here, we address the hypothesis that 5-hydroxytryptamine (5-HT) differentially stimulates afferent nerve subtypes in the oesophagus. Extracellular recordings of single unit activity originating from nerve terminals were made in the isolated innervated guinea-pig oesophagus. Whole cell patch clamp recordings (35 °C) were made from the primary afferent neurons retrogradely labelled from the oesophagus. 5-Hydroxytryptamine (10 ,mol L,1) activated vagal nodose C-fibres (70%) in the oesophagus but failed to activate overtly vagal jugular nerve fibres and oesophagus-specific spinal DRG neurons. The response to 5-HT in nodose C-fibre nerve terminals was mimicked by the selective 5-HT3 receptor agonist 2-methyl-5-HT (10 ,mol L,1) and nearly abolished by the 5-HT3 receptor antagonists ondansetron (10 ,mol L,1) and Y-25130 (10 ,mol L,1). In patch clamp studies, 2-methyl-5-HT (10 ,mol L,1) activated a proportion of isolated oesophagus-specific nodose capsaicin-sensitive neurons (putative cell bodies of nodose C-fibres). We conclude that the responsiveness to 5-HT discriminates placode-derived (vagal nodose) C-fibres from the neural crest-derived (vagal jugular and spinal DRG) afferent nerves in the oesophagus. The response to 5-HT in nodose C-fibres is mediated by the 5-HT3 receptor in their neuronal membrane. [source] PRECLINICAL STUDY: Electroacupuncture treatment reverses morphine-induced physiological changes in dopaminergic neurons within the ventral tegmental areaADDICTION BIOLOGY, Issue 4 2009Ling Hu ABSTRACT Chronic morphine administration decreases the size of dopamine (DA) neurons in the ventral tegmental area (VTA). These transient morphological changes are accompanied by a reduced sensitivity of morphine-induced conditioned place preference (CPP) after chronic exposure to the drug. In this study we examined alterations in the firing rate of DAergic neurons by means of extracellular recording following chronic morphine exposure and applied 100 Hz electroacupuncture (EA) treatment to reverse the reduced firing rate of these neurons. In the first set of experiments we show that in rats, which received chronic morphine treatment for 14 days, a small dose of morphine was not able to induce a CPP response anymore. However, the sensitivity to morphine was reinstated by consecutive EA treatment for 10 days. The electrophysiological response of VTA DA neurons to morphine was markedly reduced in chronic morphine-treated rats compared to saline-treated controls. A substantial recovery of the reactivity of VTA DA neurons to morphine was observed in rats that received 100 Hz EA for 10 days. Our findings suggest that 100 Hz EA is a potential therapy for the treatment of opiate addiction by normalizing the activity of VTA DA neurons. [source] Substance P excites globus pallidus neurons in vivoEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007Qiao-Ling Cui Abstract Substance P is a member of the neurokinin family. Previous studies have reported the existence of substance P and its high-affinity receptor, neurokinin-1 receptor, in globus pallidus. Employing in vivo extracellular recording combined with behavioural tests, the effects of substance P in globus pallidus of rats were studied. Micropressure ejection of the selective neurokinin-1 receptor agonist [Sar9,Met(O2)11] substance P increased the spontaneous firing rate of pallidal neurons in a concentration-dependent manner, with increases of 27.3% at 0.01, 33.4% at 0.03, 45.5% at 0.1, 38.4% at 0.3 and 36.4% at 1.0 mm. The selective neurokinin-1 receptor antagonist SR140333B prevented the excitatory effects induced by [Sar9,Met(O2)11] substance P. In behaving rats, we observed the postural effects of neurokinin-1 receptor activation in the globus pallidus. Consistent with electrophysiological results, unilateral microinjection of [Sar9,Met(O2)11] substance P (0.1 mm) led to a SR140333B-sensitive contralateral deflection in the presence of systemic haloperidol administration. Combining electrophysiological and behavioural findings, we concluded that substance P produces excitatory effects on globus pallidus neurons via neurokinin-1 receptors. [source] Ascending and descending brainstem neuronal activity during cystometry in decerebrate catsNEUROUROLOGY AND URODYNAMICS, Issue 4 2003Kimio Sugaya Abstract Aims This study was undertaken to examine the distribution of pontomedullary neurons related to micturition or urine storage, as well as the connections between the pontine micturition center (PMC), medullary neurons, and the spinal cord. Methods In decerebrate cats, extracellular recording of the rostral pontine and rostral medullary neurons was performed. Firing of each neuron was quantitated during cystometry. Connections between the PMC, medullary neurons, and the spinal cord (L1) were also examined electrophysiologically. Results Ninety-four neurons showed an increase or decrease of the firing rate during micturition. Units with an antidromic response to L1 stimulation and an increased firing rate were located in the nucleus locus coeruleus alpha (LCa; n,=,8) corresponding to the PMC, and in the medial reticular formation (MRF) of the medulla (n,=,14). Units showing a decreased firing rate were located in the nucleus reticularis pontis oralis (PoO; n,=,26) and in the MRF (n,=,11). The latencies of antidromic and orthodromic responses of the LCa units were longer than those of the PoO units. MRF neurons responded antidromically and/or orthodromically to stimulation of the PMC or L1. Conclusions These results suggest that the pathway concerned with urine storage has a faster spinobulbospinal loop than the micturition reflex pathway and that rostral medullary neurons also play an important role in micturition and urine storage. There may be two descending pathways between the PMC and the spinal cord: both a direct pathway and one by means of medullary neurons. Neurourol. Urodynam. 22:343,350, 2003. © 2003 Wiley-Liss, Inc. [source] Glutamine induces epileptiform discharges in superficial layers of the medial entorhinal cortex from pilocarpine-treated chronic epileptic rats in vitroEPILEPSIA, Issue 4 2009Nora Sandow Summary Purpose:, Glutamine (GLN) is a precursor for synthesis of glutamate and ,-aminobutyric acid (GABA) and has been found in the cerebrospinal fluid (CSF) at mean concentrations of 0.6 mM. Experiments on slices are usually performed in artificial CSF (aCSF) kept free of amino acids. Therefore, the role of glutamine, particularly in tissue of epileptic animals, remains elusive. Methods:, Using extracellular recordings we studied effects of GLN on field potentials and stimulus-evoked field responses in the medial entorhinal cortex (MEC) of combined entorhinal cortex hippocampal slices from pilocarpine-treated chronic epileptic rats and age-matched saline-injected control rats. Results:, In presence of GLN (0.5 and 2 mM) recurrent epileptiform discharges (REDs) were observed in slices from epileptic rats (64% and 80%, respectively), but not in slices from control rats. REDs were restricted to the superficial MEC, suppressed by the ,-Amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (30 ,M), attenuated by the inhibitor of neuronal glutamine transporters methylamino-isobutyric acid (10 mM), and apparently augmented and prolonged by the GABAA receptor antagonist bicuculline-methiodide (5 ,M). In contrast, amplitudes of stimulus evoked nonsynaptic and synaptic field responses increased in slices from control rats (+23% and +12% of the reference values) and insignificantly less or not in those of epileptic rats (+6.5% and ,0.25%, respectively). Notably, stimulus-evoked slow negative transients confined to slices of epileptic animals were reduced in amplitude (,18%). Discussion:, In combined entorhinal hippocampal slices from chronic epileptic animals, GLN induces glutamatergic REDs via neuronal uptake in superficial layers of the MEC where inhibitory function seemed to be partially preserved. [source] Propagation Dynamics of Epileptiform Activity Acutely Induced by Bicuculline in the Hippocampal,Parahippocampal Region of the Isolated Guinea Pig BrainEPILEPSIA, Issue 12 2005Laura Uva Summary:,Purpose: Aim of the study is to investigate the involvement of parahippocampal subregions in the generation and in the propagation of focal epileptiform discharges in an acute model of seizure generation in the temporal lobe induced by arterial application of bicuculline in the in vitro isolated guinea pig brain preparation. Methods: Electrophysiological recordings were simultaneously performed with single electrodes and multichannel silicon probes in the entorhinal, perirhinal, and piriform cortices and in the area CA1 of the hippocampus of the in vitro isolated guinea pig brain. Interictal and ictal epileptiform discharges restricted to the temporal region were induced by a brief (3,5 min) arterial perfusion of the GABAA receptor antagonist, bicuculline methiodide (50 ,M). Current source density analysis of laminar field profiles performed with the silicon probes was carried out at different sites to establish network interactions responsible for the generation of epileptiform potentials. Nonlinear regression analysis was conducted on extracellular recordings during ictal onset in order to quantify the degree of interaction between fast activities generated at different sites, as well as time delays. Results: Experiments were performed in 31 isolated guinea pig brains. Bicuculline-induced interictal and ictal epileptiform activities that showed variability of spatial propagation and time course in the olfactory,temporal region. The most commonly observed pattern (n = 23) was characterized by the initial appearance of interictal spikes (ISs) in the piriform cortex (PC), which propagated to the lateral entorhinal region. Independent and asynchronous preictal spikes originated in the entorhinal cortex (EC)/hippocampus and progressed into ictal fast discharges (around 25 Hz) restricted to the entorhinal/hippocampal region. The local generation of fast activity was verified and confirmed both by CSD and phase shift analysis performed on laminar profiles. Fast activity was followed by synchronous afterdischarges that propagated to the perirhinal cortex (PRC) (but not to the PC). Within 1,9 min, the ictal discharge ceased and a postictal period of depression occurred, after which periodic ISs in the PC resumed. Unlike preictal ISs, postictal ISs propagated to the PRC. Conclusions: Several studies proposed that reciprocal connections between the entorhinal and the PRC are under a very efficient inhibitory control (1). We report that ISs determined by acute bicuculline treatment in the isolated guinea pig brain progress from the PC to the hippocampus/EC just before ictal onset. Ictal discharges are characterized by a peculiar pattern of fast activity that originates from the entorhinal/hippocampal region and only secondarily propagates to the PRC. Postictal propagation of ISs to the PRC occured exclusively when an ictal discharge was generated in the hippocampal/entorhinal region. The results suggest that reiteration of ictal events may promote changes in propagation pattern of epileptiform discharges that could act as trigger elements in the development of temporal lobe epilepsy. [source] Effects of Antiepileptic Drugs on Refractory Seizures in the Intact Immature Corticohippocampal Formation In VitroEPILEPSIA, Issue 11 2003Pascale Paule Quilichini Summary:,Purpose: We developed a new in vitro preparation of immature rats, in which intact corticohippocampal formations (CHFs) depleted in magnesium ions become progressively epileptic. The better to characterize this model, we examined the effects of 14 antiepileptic drugs (AEDs) currently used in clinical practice. Methods: Recurrent ictal-like seizures (ILEs, four per hour) were generated in intact CHFs of P7,8 rats, and extracellular recordings were performed in the hippocampus and neocortex. AEDs were applied at clinically relevant concentrations (at least two), during 30 min after the third ILE. Their ability to prevent or to delay the next ILE was examined. Results: Valproic acid and benzodiazepines (clobazam and midazolam) but also phenobarbital and levetiracetam prevent the occurrence of seizures. In contrast, usual concentrations of carbamazepine (CBZ), phenytoin, vigabatrin, tiagabine, gabapentin, lamotrigine (LTG), topiramate, felbamate, and ethosuximide did not suppress ILEs. In addition, LTG and CBZ aggravate seizures in one third of the cases. Conclusions: This intact in vitro preparation in immature animals appears to be quite resistant to most AEDs. Blockade of seizures was achieved with drugs acting mainly at the ,-aminobutyric acid (GABA)A -receptor site but not with those that increase the amount of GABA. Drugs with a broad spectrum of activity are efficient but not those preferentially used in partial seizures or absences. We suggest that this preparation may correspond to a model of epilepsy with generalized convulsive seizures and could be helpful to develop new AEDs for refractory infantile epilepsies. [source] A Possible Role for Gap Junctions in Generation of Very Fast EEG Oscillations Preceding the Onset of, and Perhaps Initiating, SeizuresEPILEPSIA, Issue 2 2001Roger D. Traub Summary: ,Purpose: We propose an experimentally and clinically testable hypothesis, concerning the origin of very fast (>,70 Hz) EEG oscillations that sometimes precede the onset of focal seizures. These oscillations are important, as they may play a causal role in the initiation of seizures. Methods: Subdural EEG recordings were obtained from children with focal cortical dysplasias and intractable seizures. Intra- and extracellular recordings were performed in rat hippocampal slices, with induction of population activity, as follows: (a) bath-applied tetramethylamine (an intracellular alkalinizing agent, that opens gap junctions); (b) bath-applied carbachol, a cholinergic agonist; and (c) focal pressure ejection of hypertonic K+ solution. Detailed network simulations were performed, the better to understand the cellular mechanisms underlying oscillations. A major feature of the simulations was inclusion of axon,axon gap junctions between principal neurons, as supported by recent experimental data. Results: Very fast oscillations were found in children before seizure onset, but also superimposed on bursts during the seizure, and on interictal bursts. In slice experiments, very fast oscillations had previously been seen on interictal-like bursts; we now show such oscillations before, between, and after epileptiform bursts. Very fast oscillations were also seen superimposed on gamma (30,70 Hz) oscillations induced by carbachol or hypertonic K+, and in the latter case, very fast oscillations became continuous when chemical synapses were blocked. Simulations replicate these data, when axonal gap junctions are included. Conclusions: Electrical coupling between principal neurons, perhaps via axonal gap junctions, could underlie very fast population oscillations, in seizure-prone brain, but possibly also in normal brain. The anticonvulsant potential of gap-junction blockers such as carbenoxolone, now in clinical use for treatment of ulcer disease, should be considered. [source] Metabotropic glutamate receptor 1 activity generates persistent, N -methyl- d -aspartate receptor-dependent depression of hippocampal pyramidal cell excitabilityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2009J. P. Clement Abstract Metabotropic glutamate receptors (mGluRs) are involved in many forms of neuronal plasticity. In the hippocampus, they have well-defined roles in long-lasting forms of both synaptic and intrinsic plasticity. Here, we describe a novel form of long-lasting intrinsic plasticity that we call (S)-3,5-dihydroxyphenylglycine (DHPG)-mediated long-term depression of excitability (DHPG-LDE), and which is generated following transient pharmacological activation of group I mGluRs. In extracellular recordings from hippocampal slices, DHPG-LDE was expressed as a long-lasting depression of antidromic compound action potentials (cAPs) in CA1 or CA3 cells following a 4-min exposure to the group I mGluR agonist (S)-DHPG. A similar phenomenon was also seen for orthodromic fibre volleys evoked in CA3 axons. In single-cell recordings from CA1 pyramids, DHPG-LDE was manifest as persistent failures in antidromic action potential generation. DHPG-LDE was blocked by (S)-(+)- a -amino-4-carboxy-2-methylbenzeneacetic acid (LY367385), an antagonist of mGluR1, but not 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), an mGluR5 inhibitor. Although insensitive to antagonists of ,-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate/kainate and ,-aminobutyric acidA receptors, DHPG-LDE was blocked by antagonists of N -methyl- d -aspartate (NMDA) receptors. Similarly, in single-cell recordings, DHPG-mediated antidromic spike failures were eliminated by NMDA receptor antagonism. Long after (S)-DHPG washout, DHPG-LDE was reversed by mGluR1 antagonism. A 4-min application of (S)-DHPG also produced an NMDA receptor-dependent persistent depolarization of CA1 pyramidal cells. This depolarization was not solely responsible for DHPG-LDE, because a similar level of depolarization elicited by raising extracellular K+ increased the amplitude of the cAP. DHPG-LDE did not involve HCN channels or protein synthesis, but was eliminated by blockers of protein kinase C or tyrosine phosphatases. [source] Characterization in vivo of bilaterally branching pontocerebellar mossy fibre to Golgi cell inputs in the rat cerebellumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2009Tahl Holtzman Abstract Golgi cells regulate the flow of information from mossy fibres to the cerebellar cortex, through a mix of feedback and feedforward inhibitory actions on granule cells. The aim of the current study was to examine mossy fibre input to Golgi cells, in order to assess their impact on switching Golgi cells into feedforward behaviour. In urethane-anaesthetized rats, extracellular recordings were made from Golgi cells in Crus II (n = 18). Spikes were evoked in all Golgi cells by microstimulation within the contralateral hemispheral cortex, via branches of mossy fibres that terminate in both cerebellar hemispheres. The latencies of these responses were very short, consistent with a monosynaptic mossy fibre contact [average onset latency 2.3 ± 0.1 ms (SEM)]. The same stimuli had no measurable effect on spike responses of nearby Purkinje cells (n = 12). Systematic mapping in the contralateral cerebellar hemisphere (Crus Ib, IIa, IIb and the paramedian lobule) usually revealed one low-intensity stimulus ,hotspot' (12,35 ,A) from which short-latency spikes could be evoked in an individual Golgi cell. Microinjections of red and green retrograde tracers (latex beads, ,50,150 nL injection volume) made at the recording site and the stimulation hotspot resulted in double-labelled neurons within the pontine nuclei. Overall, this suggests that subsets of pontine neurons supply mossy fibres that branch to both hemispheres, some of which directly target Golgi cells. Such an arrangement may provide a common feedforward inhibitory link to temporally couple activity on both sides of the cerebellum during behaviour. [source] Neuronal activity in the subthalamic nucleus modulates the release of dopamine in the monkey striatumEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2009Yasushi Shimo Abstract The primate subthalamic nucleus (STN) is commonly seen as a relay nucleus between the external and internal pallidal segments, and as an input station for cortical and thalamic information into the basal ganglia. In rodents, STN activity is also known to influence neuronal activity in the dopaminergic substantia nigra pars compacta (SNc) through inhibitory and excitatory mono- and polysynaptic pathways. Although the anatomical connections between STN and SNc are not entirely the same in primates as in rodents, the electrophysiologic and microdialysis experiments presented here show directly that this functional interaction can also be demonstrated in primates. In three Rhesus monkeys, extracellular recordings from SNc during microinjections into the STN revealed that transient pharmacologic activation of the STN by the acetylcholine receptor agonist carbachol substantially increased burst firing of single nigral neurons. Transient inactivation of the STN with microinjections of the GABA-A receptor agonist muscimol had the opposite effect. While the firing rates of individual SNc neurons changed in response to the activation or inactivation of the STN, these changes were not consistent across the entire population of SNc cells. Permanent lesions of the STN, produced in two animals with the fiber-sparing neurotoxin ibotenic acid, reduced burst firing and firing rates of SNc neurons, and substantially decreased dopamine levels in the primary recipient area of SNc projections, the striatum, as measured with microdialysis. These results suggest that activity in the primate SNc is prominently influenced by neuronal discharge in the STN, which may thus alter dopamine release in the striatum. [source] The nitric oxide/cyclic guanosine monophosphate pathway modulates the inspiratory-related activity of hypoglossal motoneurons in the adult ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2008Fernando Montero Abstract Motoneurons integrate interneuronal activity into commands for skeletal muscle contraction and relaxation to perform motor actions. Hypoglossal motoneurons (HMNs) are involved in essential motor functions such as breathing, mastication, swallowing and phonation. We have investigated the role of the gaseous molecule nitric oxide (NO) in the regulation of the inspiratory-related activity of HMNs in order to further understand how neural activity is transformed into motor activity. In adult rats, we observed nitrergic fibers and bouton-like structures in close proximity to motoneurons, which normally lack the molecular machinery to synthesize NO. In addition, immunohistochemistry studies demonstrated that perfusion of animals with a NO donor resulted in an increase in the levels of cyclic guanosine monophosphate (cGMP) in motoneurons, which express the soluble guanylyl cyclase (sGC) in the hypoglossal nucleus. Modulators of the NO/cGMP pathway were micro-iontophoretically applied while performing single-unit extracellular recordings in the adult decerebrated rat. Application of a NO synthase inhibitor or a sGC inhibitor induced a statistically significant reduction in the inspiratory-related activity of HMNs. However, excitatory effects were observed by ejection of a NO donor or a cell-permeable analogue of cGMP. In slice preparations, application to the bath of a NO donor evoked membrane depolarization and a decrease in rheobase, which were prevented by co-addition to the bath of a sGC inhibitor. These effects were not prevented by reduction of the spontaneous synaptic activity. We conclude that NO from afferent fibers anterogradely modulates the inspiratory-related activity of HMNs by a cGMP-dependent mechanism in physiological conditions. [source] Altered sensorimotor development in a transgenic mouse model of amyotrophic lateral sclerosisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2004Julien Amendola Abstract Most neurodegenerative diseases become manifest at an adult age but abnormalities or pathological symptoms appear earlier. It is important to identify the initial mechanisms underlying such progressive neurodegenerative disease in both humans and animals. Transgenic mice expressing the familial amyotrophic lateral sclerosis (ALS)-linked mutation (G85R) in the enzyme superoxide dismutase 1 (SOD1) develop motor neuron disease at 8,10 months of age. We address the question of whether the mutation has an early impact on spinal motor networks in postnatal mutant mice. Behavioural tests showed a significant delay in righting and hind-paw grasping responses in mutant SOD1G85R mice during the first postnatal week, suggesting a transient motor deficit compared to wild-type mice. In addition, extracellular recordings from spinal ventral roots in an in vitro brainstem,spinal cord preparation demonstrated different pharmacologically induced motor activities between the two strains. Rhythmic motor activity was difficult to evoke with N -methyl- dl -aspartate and serotonin at the lumbar levels in SOD1G85R mice. In contrast to lumbar segments, rhythmic activity was similar in the sacral roots from the two strains. These results strongly support the fact that the G85R mutation may have altered lumbar spinal motor systems much earlier than previously recognized. [source] Induction of bilateral plasticity in sensory cortical maps by small unilateral cortical infarcts in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003S. Reinecke Abstract Behavioural impairments caused by brain lesions show a considerable, though often incomplete, recovery. It is hypothesized that cortical and subcortical plasticity of sensory representations contribute to this recovery. In the hindpaw representation of somatosensory cortex of adult rats we investigated the effects of focal unilateral cortical lesions on remote areas. Cortical lesions with a diameter of ,,2 mm were induced in the parietal cortex by photothrombosis with the photosensitive dye Rose Bengal. Subsequently, animals were kept in standard cages for 7 days. On day seven, animals were anaesthetized and cutaneous receptive fields in the cortical hindpaw representations ipsi- and contralateral to the lesion were constructed from extracellular recordings of neurons in layer IV using glass microelectrodes. Receptive fields in the lesioned animals were compared to receptive fields measured in nonlesioned animals serving as controls. Quantitative analysis of receptive fields revealed a significant increase in size in the lesioned animals. This doubling in receptive field size was observed equally in the hemispheres ipsi- and contralateral to the lesion. The results indicate that the functional consequences of restricted cortical lesions are not limited to the area surrounding the lesion, but affect the cortical maps on the contralateral, nonlesioned hemisphere. [source] Phase-coupled oscillator models can predict hippocampal inhibitory synaptic connectionsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2001F. K. Skinner Abstract What factors are responsible for propagating electrical activity in the hippocampus? Using an intact, isolated hippocampus preparation, it is possible to observe spontaneous delta (, 4 Hz) waves of rhythmic field potentials. These rhythmic potentials are inhibitory in nature, mediated by GABAergic inhibitory potentials originating from a population of principal neurons. They start in the ventro-temporal region and move longitudinally towards the dorso-septal region with a phase lag of , 10% between the extracellular recordings. We use the mathematical framework of phase-coupled oscillators (PCO) to gain some insight into the underlying network system. A chain of 15 nearest-neighbour bidirectionally coupled PCOs is used where each oscillator refers to a segment of the CA1 region of the hippocampus that can generate these slow field potentials. We find that ventro-dorsal delta waves exist if there is a dominance in coupling strength in one direction. Without a one-way coupling dominance, ventro-dorsal waves can still exist, but then the coupling strengths need to be much larger. The relationship between entrained and intrinsic frequencies and the variation of propagation speeds along the longitudinal axis can be used to determine which case applies. Currently available experimental data supports one of the cases, predicting that there is a stronger ventral to dorsal inhibitory effect. [source] In Vivo Modulation of Post-Spike Excitability in Vasopressin Cells by ,-Opioid Receptor ActivationJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2000C. H. Brown Abstract An endogenous ,-opioid agonist reduces the duration of phasic bursts in vasopressin cells. Non-synaptic post-spike depolarizing after-potentials underlie activity during bursts by increasing post-spike excitability and ,-receptor activation reduces depolarizing after-potential amplitude in vitro. To investigate the effects of ,-opioids on post-spike excitability in vivo, we analysed extracellular recordings of the spontaneous activity of identified supraoptic nucleus vasopressin cells in urethane-anaesthetized rats infused with Ringer's solution (n = 17) or the ,-agonist, U50,488H (2.5 µg/h at 0.5 µl/h; n = 23), into the supraoptic nucleus over 5 days. We plotted the mean hazard function for the interspike interval distributions as a measure of the post-spike excitability of these cells. Following each spike, the probability of another spike firing in vasopressin cells recorded from U50,488H infused nuclei was markedly reduced compared to Ringer's treated vasopressin cells. To determine whether U50,488H could reduce post-spike excitability in cells that displayed spontaneous phasic activity, we infused U50,488H (50 µg/h at 1 µl/h, i.c.v.), for 1,12 h while recording vasopressin cell activity. Nine of 10 vasopressin cells were silenced by i.c.v. U50,488H 15 ± 5 min into the infusion. Six cells exhibited spontaneous phasic activity before U50,488H infusion and recordings from three of these phasic cells were maintained until activity recovered; during U50,488H infusion, the activity of these three cells was irregular. Generation of the mean hazard function before and during U50,488H infusion revealed a reduction in post-spike excitability during U50,488H infusion. Thus, ,-receptor activation reduces post-spike excitability in vivo; this may reflect inhibition of depolarizing after-potentials and may thus underlie the reduction in burst duration of vasopressin cells caused by an endogenous ,-agonist in vivo. [source] Behavioral and electrophysiological effects of 5-HT in globus pallidus of 6-hydroxydopamine lesioned ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2010Shu-Jing Zhang Abstract Anatomical studies have shown that the globus pallidus receives abundant 5-hydroxytryptamine (5-HT) innervations from raphe nuclei. 5-HT may occupy an important position in the modulation of motor function through its affect on the activity of globus pallidus. In the present study, intrapallidal microinjection of 5-HT (0.1 mM) alone did not induce any motor behavior or postural asymmetry in the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. However, when infused concomitantly with a low dose of 3, 4-dihydroxyphenylalanine (L-DOPA, 3 mg/kg i.p.), which itself can induce modest contralateral rotational behavior, 5-HT significantly potentiated the number of contralateral rotations. To elucidate the cellular mechanism, in vivo extracellular recordings were performed to examine the effects of 5-HT on globus pallidus neurons. In normal rats, the predominant effect of micropressure ejection of 5-HT on pallidal neurons was excitation. In 6-OHDA-lesioned rats, although 5-HT increased the firing rate in most pallidal neurons, 5-HT-induced inhibitory effects was stronger than that on the unlesioned side as well as normal rats. Furthermore, 5-HT1B receptors are mainly involved in 5-HT-induced excitation while 5-HT1A receptors are involved in 5-HT-induced inhibition. The results suggest that 5-HT may potentiate the antiparkinsonian effect of L-DOPA through modulating the activity of globus pallidus. © 2009 Wiley-Liss, Inc. [source] The Mammalian Circadian Clock Exhibits Acute Tolerance to EthanolALCOHOLISM, Issue 12 2009Rebecca A. Prosser Background:, Tolerance to ethanol is observed over a variety of time courses, from minutes to days. Acute tolerance, which develops over 5 to 60 minutes, has been observed for both behavioral and neurophysiological variables and may involve changes in signaling through NMDA, GABA, or other receptors. Previous work has shown that both acute and chronic ethanol treatments modulate photic and nonphotic phase resetting of the mammalian circadian clock located in the suprachiasmatic nucleus (SCN). Although not specifically tested, the data thus far do not point to the development of chronic tolerance to the modulatory effects of ethanol. Here we investigated whether acute tolerance the ethanol occurs with respect to in vitro phase modulation of the SCN clock. Methods:, Mouse brain slices containing the SCN were pretreated with ethanol for varying lengths of time, followed by treatment concurrent with either glutamate or the serotonin agonist, 8-hydroxy-DPAT (DPAT). The phase of the SCN circadian clock was assessed the following day through extracellular recordings of SCN neuronal activity. SCN neuronal activity normally peaks during mid-day, and this rhythm can be shifted by treatment with either glutamate or DPAT. Results:, While concurrent treatment of SCN-containing brain slices with ethanol and glutamate blocks glutamate-induced phase delays of the SCN clock, pretreating the slices with ethanol for ,15 minutes prevents this inhibition. Likewise, while concurrent treatment with ethanol and DPAT enhances DPAT-induced phase advances of the SCN clock, pretreating the slices with ethanol for ,30 minutes prevents this enhancement. Conclusions:, Both the inhibiting and enhancing effects of ethanol on in vitro SCN clock phase resetting show acute tolerance. Additional experiments are needed to determine whether more slowly developing forms of tolerance also occur with respect to the SCN circadian clock. [source] Evidence that 5-hydroxytryptamine7 receptors play a role in the mediation of afferent transmission within the nucleus tractus solitarius in anaesthetized ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2009Diana Oskutyte Background and purpose:, Central 5-hydroxytryptamine (5-HT)-containing pathways utilizing 5-HT7 receptors are known to be critical for the mediation of cardiovascular reflexes. The nucleus tractus solitarius (NTS) is a site involved in the integration of cardiovascular afferent information. The present experiments examined the involvement of the 5-HT7 receptor in the processing of cardiovascular reflexes in the NTS. Experimental approach:, In anaesthetized rats extracellular recordings were made from 104 NTS neurones that were excited by electrical stimulation of the vagus nerve and/or activation of cardiopulmonary afferents. Drugs were applied ionophoretically in the vicinity of these neurones. Key results:, The non-selective 5-HT7 receptor agonist 5-carboxamidotryptamine maleate (5-CT) applied to 78 neurones increased the firing rate in 18 by 59% and decreased it in 38 neurones by 47%. Similarly, the 5-HT1A agonist 8-OH-DPAT applied to 20 neurones had an excitatory (8), inhibitory (7) or no effect (5) on the 20 neurones tested. In the presence of the 5-HT7 antagonist SB 258719 the 5-CT excitation was attenuated. Furthermore, the excitatory response of NTS neurones evoked by electrical stimulation of the vagus nerve or activation of cardiopulmonary afferents with intra atrial phenylbiguanide was attenuated by SB 258719. The inhibitory action of 5-CT was unaffected by SB 258719 and the 5-HT1A antagonist WAY-100635. WAY-100635 failed to have any effect on 5-CT and vagal afferent-evoked excitations. Conclusions and implications:, Vagal afferent-evoked excitation of NTS neurones can be blocked by SB 258719, a selective 5-HT7 antagonist. This observation further supports the involvement of 5-HT neurotransmission in NTS afferent processing. [source] Attenuation of acute and chronic effects of morphine by the imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline in rat locus coeruleus neuronsBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2003Eduardo Ruiz-Durántez The aim of this study was to determine if 2-(2-benzofuranyl)-2-imidazoline (2-BFI) interacts with the opioid system in the rat locus coeruleus, using single-unit extracellular recordings. In morphine-dependent rats, acute administration of the selective imidazoline receptor ligands 2-BFI (10 and 40 mg kg,1, i.p. and 100 ,g, i.c.v.) or valldemossine (10 mg kg,1, i.p.) did not modify the naloxone-induced hyperactivity of locus coeruleus neurons compared with that observed in the morphine-dependent control group. After chronic administration of 2-BFI (10 mg kg,1, i.p., three times daily, for 5 days) and morphine, naloxone-induced hyperactivity and tolerance to morphine were attenuated. This effect was not observed when a lower dose of 2-BFI (1 mg kg,1, i.p.) or valldemossine (10 mg kg,1, i.p.) were used. Acute administration of 2-BFI (10 and 40 mg kg,1, i.p. and 100 ,g, i.c.v.) but not valldemossine (40 mg kg,1, i.p.) diminished the potency of morphine to inhibit locus coeruleus neuron activity in vivo (ED50 values increased by 2.3, 2.9; and 3.1 fold respectively). Similarly, the potency of Met5 -enkephalin to inhibit locus coeruleus neurons was decreased when 2-BFI (100 ,M) was applied to rat brain slices (EC50 increased by 5.6; P<0.05). The present data demonstrate that there is an interaction between 2-BFI and the opioid system in the locus coeruleus. This interaction leads to an attenuation of both the hyperactivity of locus coeruleus neurons during opiate withdrawal and the development of tolerance to morphine when 2-BFI is chronically administered. These results suggest that imidazoline drugs may prove to be useful agents for the management of opioid dependence and tolerance. British Journal of Pharmacology (2003) 138, 494,500. doi:10.1038/sj.bjp.0705052 [source] | |||||||||||||