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U Misgeld

Publications and source records attributed to U Misgeld.

At least 73 records · Page 4Linked to original sources
PubMed1989

Effects of (-)baclofen on inhibitory neurons in the guinea pig hippocampal slice.

Intracellular recordings were made from electrophysiologically identified inhibitory neurons in the dentate hilus. (-)Baclofen (0.1-0.5 mumol/l), applied by the bath, strongly hyperpolarized inhibitory neurons, reduced their input resistance and induced outward currents under voltage clamp at holding potentials of -60 mV in cells recorded with KCl-filled electrodes. Increasing the (-)baclofen concentration (up to 1 mumol/l) did not increase the amplitude of the outward current, but increased its duration. (-)Baclofen depressed Cl-dependent IPSPs evoked by perforant path stimulation in inhibitory neurons, granule cells and CA3 neurons. In the case of inhibitory neurons and CA3 neurons, depression of IPSPs, membrane hyperpolarization and increase in membrane conductance concurred. All effects were blocked by BaCl2 (1 mmol/l) in the superfusate. In the case of granule cells, depression of IPSPs by (-)baclofen outlasted an only small membrane hyperpolarization, conductance increase or outward current. High concentrations (up to 10 mumol/l) of (-)baclofen depressed evoked IPSPs of granule cells for an extended period of time, but the other effects remained small and transient. IPSPs elicited in granule cells by microdrop application of glutamate to the dentate hilus were also blocked by (-)baclofen, but spontaneous IPSPs were only reduced in amplitude. We suggest that the blockade of GABAA receptor-mediated IPSPs of hippocampal neurons by the GABAB receptor agonist (-)baclofen can be explained by a K-dependent hyperpolarization of inhibitory neurons.

Animals↗
PubMed1989

Potentiation and suppression by eserine of muscarinic synaptic transmission in the guinea-pig hippocampal slice.

1. The effects of the anticholinesterase eserine on CA3 pyramidal cells and dentate gyrus granule cells in guinea-pig hippocampal slices were investigated with single-electrode current-clamp and voltage-clamp recording. 2. In the majority of cells superfused with eserine (0.5-10 microM) for 3-10 min, tetanic stimulation near the cell layers elicited a delayed depolarization (slow EPSP; duration up to 60 s) at a pre-stimulation membrane potential of -60 mV. The slow EPSP was blocked by atropine (1 microM). 3. Under voltage clamp at -60 mV holding potential, an apparent inward current (slow EPSC) with a similar time course to the slow EPSP was observed. 4. The amplitude of the delayed inward current was about 50 pA. The amplitude increased at holding potentials more positive than -60 mV. At holding potentials negative to -60 mV, the delayed inward current was too small to allow reliable analysis. In the absence of eserine, there was a delayed inward current, which was rather small, however, due to a superimposed outward current. 5. Eserine reduced the after-hyperpolarization following a train of action potentials. This effect was antagonized by atropine, but not to pirenzepine. In voltage-clamp recording, eserine reduced a current termed IAHP. 6. CA3 neurones treated with eserine exhibited a region of negative slope conductance (in tetrodotoxin). The slow inward current which developed at clamp potentials between -50 and -40 mV was reduced by Ni2+ (50 microM). The effect of eserine on slope conductance increased with time of exposure. In all neurones superfused with eserine for more than 60 min, burst discharges were observed. Burst discharges were blocked by atropine and Ni2+, but not by pirenzepine. 7. In cells superfused with eserine for more than 1 h, tetanic stimulation failed to elicit a slow EPSP or EPSC. Currents induced by focal acetylcholine (ACh) application were first enhanced by eserine, but blocked after exposure to eserine for more than 1 h. Blockade of ACh-induced currents was also observed after bath application of carbachol (CCh) in a concentration (0.2 microM) in which it did not induce an inward current at -60 mV holding potential. Further, the slow EPSP faded when elicited by repeated tetanic stimulation. 8. While the observed effects of eserine on hippocampal neurones can be explained by eserine's well-known ability to block acetylcholinesterase activity, our data indicate that the effects of eserine involve more than one muscarinic receptor site, i.e. desensitizing and non-desensitizing postsynaptic receptor sites.

Action Potentials↗
PubMed1988

Muscarinic inhibitory effect in the guinea pig dentate gyrus in vitro.

Various drugs known to affect synaptic transmission were tested for their effects on extracellular field potentials evoked in the dentate granule cell layer of guinea pig hippocampal slices. Presumptive commissural (CF) and perforant path (PP) fibers were stimulated electrically by two separate pairs of stimulating electrodes. CF stimulation elicited a field potential with a current sink and PP stimulation with a current source in the cell layer. Bath-applied carbachol (0.5-10 microM), in an atropine sensitive manner, depressed the CF-evoked field potential, but left the PP-evoked field potential unchanged. Further pharmacological testing revealed that this effect is likely to be mediated by inhibitory neurons in the dentate hilus.

Animals↗
PubMed1988

Carbachol effects on hippocampal neurons in vitro: dependence on the rate of rise of carbachol tissue concentration.

Nominally K-sensitive microelectrodes were used to measure carbachol (CCh) in order to study the dependence of muscarinic effects on CCh concentration and exposure time in guinea pig hippocampal slices. Interference presumably originating from tissue choline-compounds was neutralized by pre-equilibration of the slices with 500 microM choline and calibration of the CCh-sensitive microelectrodes in the presence of the same choline-concentration. Muscarinic depolarization and reduction of the afterhyperpolarization (AHP) following a train of action potentials by bath applied CCh were monitored in granule cells and CA3 pyramidal neurons by intracellular recording. A fast bath application mode of CCh was designed, by which CCh tissue concentration reached a peak after 2-3 min and was washed out with a half time of about 8 min. After application of 30 nmol CCh in this way, the AHP was reduced according to the variation of CCh concentration over time. Neurons depolarized with some delay after the reduction of the AHP and started to repolarize 1 min before the peak of tissue CCh concentration (0.6 microM) was reached. Pirenzepine (1-10 microM) blocked only the depolarization, while atropine (1-10 microM) blocked both the depolarization and the reduction of the AHP. When superfusing with CCh containing saline, 80% of the final concentration was reached in the bath after 12 min, but in the tissue only after 45 min. The slow increase of tissue CCh concentration was concurrent with the slow decrease of the AHP. No effect on the membrane potential was observed. Atropine, but not pirenzepine, blocked the reduction of the AHP. Superfusion with a high CCh concentration (100-300 microM) containing saline depolarized neurons and reduced the AHP. Then pirenzepine repolarized neurons, whereas atropine both repolarized the cells and restored the AHP. It is concluded tha the muscarinic depolarization depends not only on the CCh concentration, but also on the rate of rise of CCh, while the reduction of the AHP depends solely on the concentration. This result is discussed in terms of the possibility that the depolarization is mediated by a short term desensitizing M1 muscarinic receptor subtype and the reduction of the AHP is mediated by a M2 muscarinic receptor subtype.

Animals↗
PubMed1987

Intrinsic membrane properties of neostriatal neurons can account for their low level of spontaneous activity.

Electroresponsiveness of neostriatal neurons was studied by intracellular recording in a rat brain slice preparation maintained in standard solution or in solution containing K-channel blockers. In standard solution, the neurons fired repetitively at increasing frequencies with increasing amplitude of direct depolarization. The firing pattern was independent of the membrane potential from which firing was induced. In the presence of tetraethylammonium (20 mM), long-lasting (300-500 ms) plateau potentials could be elicited by the injection of short (5-10 ms) current pulses. Plateau potentials persisted in Na-free solution, in the presence of tetrodotoxin (1-3 microM) and if Ca in the perifusate was replaced by Ba. The plateau was blocked by Cd (500 microM). The plateaux were followed by depolarizing after-potentials. When the plateau potential failed due to fatigue, a small slow depolarization of short duration (10-30 ms) was elicited in Na-free or tetrodotoxin-containing solution, which increased in amplitude with membrane hyperpolarization. This slow depolarization was blocked by Cd, indicating that it was also mediated by Ca. By intrastriatal stimulation in the presence of 4-aminopyridine a long-lasting, voltage-dependent depolarization was triggered from the enhanced postsynaptic potential. In contrast, in the presence of tetraethylammonium, postsynaptic potentials were only slightly increased if they were compared at sizes subthreshold for the plateau potentials. It is concluded that neostriatal neurons, although being characterized as "silent" and "non-bursting", possess slow conductances for inward currents which they share with other mammalian central neurons. However, in contrast, to other central neurons, their Ca-spikes are suppressed by their K-conductances and, in contrast to oscillating neurons, low-threshold Ca-potentials are not prominent.

Animals↗
PubMed1986

Slow cholinergic excitation of guinea pig hippocampal neurons is mediated by two muscarinic receptor subtypes.

Stimulation of cholinergic fibers or bath application of carbachol (0.1-10 microM) induced a slow excitability increase in CA3 neurons and dentate granule cells of hippocampal slices. This effect which was antagonized by atropine (1 microM) was mediated by two receptor subtypes: a pirenzepine (10 microM)-insensitive receptor, 'M2', and a pirenzepine (1 microM)-sensitive receptor, 'M1'. The M2-receptor activation led to a blockade of slow afterhyperpolarizations following trains of action potentials and to the occurrence of threshold-activated plateau-depolarizations associated with a conductance increase. The M1-receptor mediated a membrane depolarization sometimes associated with a conductance decrease which reversed its polarity at membrane potentials negative to -80 mV. The 'slow excitatory postsynaptic potential' which results from activation of cholinergic fibers is thus caused by the activation of two receptor subtypes.

Animals↗
PubMed1986

The role of chloride transport in postsynaptic inhibition of hippocampal neurons.

Hippocampal inhibitory postsynaptic potentials are depolarizing in granule cells but hyperpolarizing in CA3 neurons because the reversal potentials and membrane potentials of these cells differ. Here the hippocampal slice preparation was used to investigate the role of chloride transport in these inhibitory responses. In both cell types, increasing the intracellular chloride concentration by injection shifted the reversal potential of these responses in a positive direction, and blocking the outward transport of chloride with furosemide slowed their recovery from the injection. In addition, hyperpolarizing and depolarizing inhibitory responses and the hyperpolarizing and depolarizing responses to the inhibitory neurotransmitter gamma-aminobutyric acid decreased in the presence of furosemide. These effects of furosemide suggest that the internal chloride activity of an individual hippocampal neuron is regulated by two transport processes, one that accumulates chloride and one that extrudes chloride.

Animals↗
PubMed1986

Muscarinic modulation of calcium dependent plateau potentials in rat neostriatal neurons.

Intracellular recording from neostriatal neurons in rat brain slices revealed effects of the acetylcholine (ACh) agonist carbachol (Cch, 1-10 mumol/l), of the anticholinesterase physostigmine (10 mumol/l) and of the muscarinic antagonist atropine (10 mumol/l) on plateau potentials elicited in the presence of K-blockers. Plateau potentials elicited in the presence of K-blockers were Ca-dependent, since they persisted in Na-free solution, were resistant to tetrodotoxin (TTX, 3 mumol/l) and blocked by Cd (0.1-0.5 mmol/l). Cch reduced the duration of the plateau potentials and made them more susceptible to fatigue. These effects were antagonized by atropine (1-10 mumol/l), but not by Ba (100-200 mumol/l) or 4-aminopyridine (4-AP, 0.5 mmol/l). Physostigmine (10 mumol/l) had the same atropine-sensitive effects as Cch on the plateau potential. Atropine (10 mumol/l), by itself, prolonged the duration of the plateau potential. High concentrations (100 mumol/l) of Cch did not further reduce the duration of the plateau potential, instead, the duration re-increased with prolonged exposure. The re-increase of the plateau-spike duration was later masked by bursting activity. The opposing effects of low and high concentrations of Cch on the plateau potential duration corresponded to effects of this drug on intrastriatally evoked EPSPs in that low concentrations of Cch reduced the EPSP amplitude, but high concentrations re-increased it after a transient decrease. It is concluded that the muscarinic effect of ACh in the neostriatum is to modulate Ca-influx and that this effect is exerted in a tonic manner.

Acetylcholine↗
PubMed1986

Late development of intrinsic excitation in the rat neostriatum: an in vitro study.

Functional maturation of intrinsic circuitry in the neostriatum was studied by intracellular recording and intracellular staining with Lucifer yellow in slices obtained from rat pups at postnatal days (P)1-20 and from adult rats. The most striking observation was that intrastriatal stimulation elicited predominantly inhibitory responses in slices obtained from animals of P1-6. In contrast, intrastriatally evoked responses in slices obtained after P10 were predominantly excitatory. The inhibitory postsynaptic potentials (IPSPs) recorded in slices obtained from pups were blocked by bicuculline (50 microM) and exhibited a reversal potential at about -60 mV which shifted in depolarizing direction when intracellular Cl- activity increased. Thus, these IPSPs correspond to IPSPs observed in adult animals. It is concluded that maturation of excitatory synapses is the main change during postnatal development. The changes of postsynaptic potentials were paralleled by the appearance of spines on dendrites around P7 as revealed by intracellular staining. The apparent input resistances and time constants of young neurons were very high and responses to large current injections were often distorted by humps which could not be observed in adult neurons. Only young neurons responded with bursts to synaptic activation in the presence of bicuculline (50 microM). It appears that dendritic conductances have a stronger influence on somatic discharge in the electrotonically compact young neurons than in adult neurons.

Animals↗
PubMed1986

Postsynaptic-GABAergic inhibition of non-pyramidal neurons in the guinea-pig hippocampus.

Intracellular recording and staining was applied to study non-pyramidal neurons in the guinea-pig hippocampus. To avoid accidental impalement of pyramidal or granule cells, two hippocampal regions known to be devoid of pyramidal or granule cells were chosen. In transverse and longitudinal slices, neurons of the deep hilar region (zone 4 of Amaral3), and in transverse slices, neurons of the stratum lacunosum-moleculare (CA3) were impaled. The intracellular staining with Lucifer Yellow revealed that of 20 neurons stained in these zones all were non-pyramidal neurons. Hilar neurons, situated just below the granular layer, differed from granule cells and CA3 neurons with respect to their action potential waveform and their current/voltage relationship. In contrast to granule cells, hilar neurons exhibited spontaneous bursts in the presence of bicuculline (25 microM). In all neurons impaled in the hilar region and the stratum lacunosum-moleculare (n = 42), inhibitory postsynaptic potentials could be elicited. These inhibitory postsynaptic potentials were blocked by bicuculline. In transverse slices, perforant path stimulation elicited inhibition preceding excitation in hilar neurons and excitation preceding inhibition in granule cells. Since non-pyramidal neurons are likely to be inhibitory neurons, our data suggest that GABAergic neurons in the hilus or in the stratum lacunosum-moleculare are controlled by inhibitory GABAergic synapses. This was verified by immunocytochemistry using antibodies against glutamate decarboxylase, the gamma-aminobutyric acid synthetizing enzyme. In both hippocampal regions studied, glutamate decarboxylase-positive synaptic terminals on glutamate decarboxylase-positive cells were observed. It is concluded that disinhibition is an important feature of information processing in the hippocampus, and that disinhibition is mediated by GABAergic synapses on GABAergic neurons.

Action Potentials↗
PubMed1986

Muscarinic slow excitation and muscarinic inhibition of synaptic transmission in the rat neostriatum.

Intracellular recording from neurones in rat neostriatal slices was used to compare the muscarinic effects of endogenous acetylcholine (ACh) released from cholinergic neostriatal synapses with the action of exogenously applied muscarinic agonists. Repetitive electrical stimulation in the neostriatum evoked a series of fast excitatory post-synaptic potentials (e.p.s.p.s) followed by a short, variable period of input resistance decrease. In the presence of the acetylcholinesterase (AChE) inhibitor, physostigmine, these potentials were followed by a slow e.p.s.p. which lasted about 60 s. Higher stimulus intensities were needed to elicit the slow e.p.s.p. than the fast e.p.s.p. The slow e.p.s.p. could not be observed after a single stimulus. Its amplitude was graded and increased with stimulus strength. The slow e.p.s.p. was blocked by the muscarinic antagonist atropine (10 microM) and by Ba2+ (100 microM). Input resistance increased during the slow e.p.s.p. Depolarization of the cell increased the size of the slow e.p.s.p. and hyperpolarization decreased it. Simultaneously, resting input resistance increased with membrane depolarization and decreased with membrane hyperpolarization. Repetitive intrastriatal stimulation was followed by a hyperpolarization instead of the depolarization at membrane potentials negative to -75 mV. Input resistance increased during this hyperpolarization as it did during the slow e.p.s.p. The slow e.p.s.p. persisted at membrane potentials of -70 to -80 mV if K+ concentration in the saline was reduced from 5 to 2 mM. In 10 mM-K+, the repetitive stimulation was followed by a hyperpolarization even at membrane potentials as low as -60 to -50 mV. Bath perfusion of high concentrations (100 microM) of muscarine or carbachol induced a sustained increase in the input resistance. The muscarinic agonists also reduced the amplitude of intrastriatally evoked fast e.p.s.p.s; however, this effect was transient and compensated by the increase in input resistance. The effects of the muscarinic agonists on input resistance and e.p.s.p. amplitude were antagonized by atropine (10 microM). Sustained decreases of e.p.s.p. amplitude were induced by the bath application of low doses (0.5-10 microM) of muscarine or carbachol. Input resistance was not altered. Atropine (1-10 microM) antagonized this effect. A sustained reduction of fast e.p.s.p. amplitude resulted also from inhibition of AChE by application of physostigmine (1-100 microM). Input resistance and neuronal excitability were not affected by AChE blockade.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1984

Differences in baclofen-sensitivity between CA3 neurons and granule cells of the guinea pig hippocampus in vitro.

In the slice preparation of the guinea pig hippocampus, the effects of (+/-) baclofen added to the Krebs-Ringer solution on dentate granule cells and CA3 pyramidal cells were investigated by means of intracellular recording techniques. In a 10-25 microM concentration, baclofen reduces the inhibitory postsynaptic potentials of the granule cells evoked by electrical stimulation of the perforant path and hyperpolarizes the granule cell membrane slightly. The reduction of both, the excitatory and inhibitory postsynaptic potentials of CA3 pyramidal cells evoked by mossy fiber stimulation, however, is accompanied by a strong hyperpolarization and conductance increase. Further, repetitive discharges of granule cells elicited in the presence of the convulsant bicuculline (25 microM) are hardly affected by baclofen (50 microM), whereas those of CA3 neurons are blocked.

Animals↗
PubMed1984

Identification of projecting neurons in rat neostriatal slices.

Spiny neurons projecting to substantia nigra (SN) were identified by combining retrograde transport of tracers in vivo with intracellular staining in vitro. First, neostriatal projection neurons were retrogradely labeled by the injection of fluorescent tracers into the ipsilateral SN. Then, slices were taken from the neostriata containing the retrogradely labeled cells. Cells were impaled for intracellular recording and stained by intracellular dye injection. All cells were of the spiny type and 75% contained both dyes, the intracellularly injected dye as well as the retrogradely transported tracer. Thus, most intracellular recordings in neostriatal slices are obtained from spiny neurons projecting to SN.

Animals↗
PubMed1984

Presynaptic muscarinic modulation of nicotinic excitation in the rat neostriatum.

In rat neostriatal slices, cholinergic agents were tested for their effects on endogenous ACh release and on electrical activity. ACh release was evoked by 25 mM K+ during two 5-min periods between which a slice was allowed to rest for 20 min; drugs were present during the second stimulation period. In the absence of a cholinesterase inhibitor, only Ch outflow was monitored. For the recording of electrical activity, intrastriatal stimulation evoked field potentials which were monitored in the absence and presence of drugs in the perfusate. Atropine (1-100 microM) increased endogenous ACh release by 32-91% and effective doses were 10-fold lower in the presence of a cholinesterase inhibitor. Atropine also increased the amplitudes of synaptic population spikes in the field potentials. The muscarinic agonists muscarine (100 microM) and oxotremorine (25 and 100 microM) decreased endogenous ACh release. Atropine (10 microM) blocked the depressant effect of muscarine (100 microM). Muscarine (100 microM-1 mM) and oxotremorine (10-100 microM) decreased the electrically evoked excitation in the rat neostriatal slices, and their effects were reversed by atropine. Only higher concentrations of nicotine (1 and 5 mM) decreased the synaptic population spikes, but potassium-stimulated Ch outflow was not affected. It is concluded that in the neostriatum presynaptic muscarinic receptors modulate nicotinic excitation since potassium-stimulated ACh release and intrinsically evoked synaptic excitation are influenced by muscarinic drugs in the same way.

Acetylcholine↗
PubMed1983

Retrograde labeling of striato-nigral neurons in the rat by three different tracers.

The three tracers horseradish peroxidase (HRP), 4',6-diamidino-2-phenylindol-2HCl (DAPI) and Fast Blue (FB) differ in retrograde labeling of striato-nigral neurons. After a 24 h survival, injection of DAPI into the ventral tegmentum labeled numerous cells throughout the neostriatum, whereas an identical amount of HRP only labeled cells in circumscribed areas of the neostriatum. Injections of FB labeled a substantial number of neostriatal neurons after a survival time of 4 days, but not after 24 h. In addition, differences between retrograde staining of striato-nigral neurons and layer V pyramidal cells of the ipsilateral neocortex, also labeled in these experiments, were found.

Amidines↗