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M Mühlethaler

Publications and source records attributed to M Mühlethaler.

54 records · Page 3Linked to original sources

Medial vestibular nucleus in the guinea-pig. II. Ionic basis of the intrinsic membrane properties in brainstem slices.

In the preceding paper, medial vestibular nuclei neurones (MVNn) were shown to belong to two main classes, A MVNn and B MVNn, depending on their membrane properties in brainstem slices. In the following study we attempted to confirm this segregation by studying some of the ionic conductances that these cells are endowed with. Type A MVNn demonstrated small high threshold calcium spikes that could be potentiated by barium, a 4-AP resistant A-like conductance and a calcium-dependent afterhyperpolarization. Type B MVNn, in contrast, had large high threshold calcium spikes and prolonged calcium-dependent plateau potentials. In addition, they had a calcium-dependent afterhyperpolarization as well as a subthreshold persistent sodium conductance. A subpopulation of B MVNn had also low threshold calcium spikes that gave them bursting properties. These data confirm the segregation of MVN neurones into two main classes and will be discussed with respect to the firing characteristics of vestibular neurones in vivo.

4-Aminopyridine↗

Electrophysiology and lucifer yellow injection of nucleus gigantocellularis neurones in an isolated and perfused guinea pig brain in vitro.

Intracellular recordings from nucleus gigantocellularis (NGC) neurones were obtained in isolated and perfused whole brains of guinea pigs in vitro. A majority of cells (90%) were characterized by an action potential of short duration (0.3 ms) followed first by a fast and then by a slower afterhyperpolarization (AHP). Their firing pattern was mostly irregular. These cells were shown to have high threshold calcium spikes and plateau potentials. The other cell type represented only 10% of the recorded cells in the NGC. It was characterized by a wider (0.6 ms) action potential, a large single AHP, the presence of a transient rectification presumably due to an A-current and a rather regular resting discharge. Using Lucifer yellow injections in brainstem slices, both cell types were shown to correspond to gigantocellular neurones.

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Opiates inhibit pedunculopontine neurones in guinea pig brainstem slices.

Intracellular recordings were obtained from pedunculopontine neurones in guinea-pig brainstem slices. These cells were characterized by a broad action potential, an A-like conductance and fired spontaneously in a regular manner. These neurones were inhibited by bath-application of both carbachol and serotonine at concentrations of 10(-4) M. Opioid peptides induced a dose-dependent hyperpolarization and a reduction in the spontaneous firing. These latter effects could be blocked by the opiate antagonist naloxone and were direct as they persisted in presence of tetrodotoxine or high magnesium/low calcium-containing salines. They were mediated by an opiate receptor of the mu type since they were obtained with the mu-preferring enkephalin analogues FK 33-824 and DAGO, but neither with the delta nor the kappa analogues such as DPLPE or U-50,488.

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Thalamic spindles in an isolated and perfused preparation in vitro.

Intracellular recordings were obtained from thalamic nuclei neurones in isolated and perfused whole brains of adult guinea pigs in vitro. Thalamic neurones presented the same basic membrane properties in this preparation as in slices. The majority of cells displayed, in addition, spontaneous spindle oscillations similar to those observed in the cat in vivo. This activity could be blocked by the cholinergic agonist carbachol perfused at 10(-4) M. Thalamic spindles could also be recorded in decorticated preparations, in which perfusion to the cerebral cortex was interrupted. Such preparations could be useful for studying in vitro the spindle generating mechanism in rodents as well as some aspects of brainstem/diencephalic interactions related to the control of sleep and arousal.

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Histamine excites pedunculopontine neurones in guinea pig brainstem slices.

Intracellular recordings were obtained from pedunculopontine tegmental nuclei neurones in guinea pig brainstem slices. These neurones were characterized by the presence of a slow regular firing (around 3 spikes/s), a broad action potential (more than 1 ms) and a transient rectification indicating the presence of an A current. Bath-application of histamine at 10(-4) or 10(-5) M induced a reversible increase in spontaneous firing. In presence of tetrodotoxin (1 microM), the effect of histamine was a reversible membrane depolarization. It was a direct effect as it persisted in presence of a low calcium/high magnesium solution. This excitatory action was presumably mediated by histamine H1 receptors as it could be blocked by the H1 receptor antagonist mepyramine but not by the H2 receptor antagonist cimetidine. A role in arousal is discussed.

Action Potentials↗

Low threshold calcium spikes in medial vestibular nuclei neurones in vitro: a role in the generation of the vestibular nystagmus quick phase in vivo?

Intracellular recordings were obtained from medial vestibular nuclei neurones in guinea-pig brainstem slices. A subpopulation of neurones in this nucleus was found to have burst firing properties. Using ionic channel blockers the underlying mechanism was shown to be a low threshold calcium spike. It is speculated that this property could be implicated in the generation of the quick phase of the vestibular nystagmus in the behaving guinea-pig.

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Design of a microprocessor-controlled thermoregulated chamber for perfusing in vitro mammalian brain preparations.

A system is described that allows to perfuse in vitro isolated mammalian brain preparations obtained from adult guinea-pigs. It consists of a microprocessor controlled thermoregulation unit, a perfusion line and a perfusion/recording chamber. The main features of the thermoregulation unit include the ability to maintain stable temperatures between 10 and 37 degrees C and to precisely control the time course of the temperature changes. Using this system, perfused tissue blocks can be kept viable for 8-10 h.

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An electrophysiological study of the in vitro, perfused brain stem-cerebellum of adult guinea-pig.

1. We describe here a technique which allows the long-term in vitro survival of the perfused isolated brain stem-cerebellum of adult guinea-pig. The viability of this preparation was assessed by comparing the electrophysiological properties of individual neurones and of neuronal pools to those obtained in vivo or in brain slices. The areas investigated included the cerebellar cortex, the inferior olive and the pontine nuclei. 2. Cerebellar field potential and intra- and extracellular single-cell recordings could be obtained for as long as 15 h after the preparation was initially isolated. The waveforms of field potentials recorded at various depths in the cerebellar cortex following surface folial stimulation were similar to those recorded in vivo. Extracellular recordings from single Purkinje cells following white matter stimulation demonstrated antidromic as well as mossy- and climbing fibre-mediated excitation. Stimulation of the cerebellar surface elicited orthodromic parallel fibre excitation of Purkinje cells and basket-stellate and Golgi cell inhibition. 3. Intrasomatic and intradendritic recordings from Purkinje cells reproduced all the phenomenology described earlier under in vivo conditions and in vitro slice preparations. In addition, spontaneous excitatory synaptic potentials generating simple spikes (mossy fibre-parallel fibre-mediated activity) and complex spikes (climbing fibre-mediated activity) were consistently observed. 4. Extracellular field potentials and extra- and intracellular recordings from inferior olive neurones were similar to those previously shown for the mammalian inferior olive. 5. Intracellular recordings were also obtained from pontine nuclei neurones, a major source of mossy fibre afferents to the cerebellum. Stimulation of the contralateral superior cerebellar peduncle produced antidromic invasion of these neurones whereas stimulation of the ipsilateral inferior cerebral peduncle resulted in their orthodromic activation. 6. The preparation responded to pharmacological challenge in a manner which demonstrated a sequential activation of sets of synaptic links in a given pathway. Thus, harmaline generated oscillations of inferior olivary neurones which were similar to those observed in vivo and which produced climbing fibre EPSPs in Purkinje cells at the same frequency as the inferior olivary oscillations. Climbing fibre activation of the Purkinje cells generated powerful inhibitory potentials in the cerebellar nuclear neurones at the same frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

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Electrophysiology of guinea-pig cerebellar nuclear cells in the in vitro brain stem-cerebellar preparation.

1. Intracellular recordings were obtained from cerebellar nuclear neurones in the isolated brain stem-cerebellar preparation of guinea-pigs in vitro. The electrical properties of the cells were quite similar to those reported in in vitro slice studies. They had an average resting potential of -56.7 +/- 1.8 mV, an input resistance of 23.8 +/- 4.9 M omega, and a time constant of 12.5 +/- 2.7 ms. The action potentials had an average amplitude of 57.3 +/- 5.28 mV (n = 20). 2. In addition to the ionic mechanisms required for the generation of the fast action potential, cerebellar nuclear neurones displayed a low-threshold Ca2+-dependent spike which produced a powerful rebound excitation following anodal break. This type of electroresponsiveness was absent in the slice preparation. 3. The anodal break response was further enhanced by the presence of a non-inactivating Na+ conductance similar to that described in Purkinje cells. 4. Following electrical stimulation of the cerebellar cortex or the underlying white matter, excitatory and inhibitory synaptic potentials (EPSP-IPSP sequences) could be recorded in cerebellar nuclear neurones. The EPSPs were elicited by direct activation of collaterals of mossy or climbing fibre afferents. The IPSPs followed direct or orthodromic Purkinje cell activation. 5. The integrity of the olivo-cerebellar system was tested by the administration of harmaline which produced powerful EPSP-IPSP sequences or pure IPSPs in cerebellar nuclear neurones. These IPSPs were often followed by a rebound firing of the cells. 6. These results indicate that the olivo-cerebellar pathway, in addition to its activation of the cerebellar cortex, exerts a powerful and complex set of synaptic events on cerebellar nuclear cells. As such it is a true afferent system, having a distinct role in cerebellar physiology.

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Contrasting effects of neurohypophysial peptides on pyramidal and non-pyramidal neurones in the rat hippocampus.

Oxytocin and vasopressin increased the rate of firing of a class of presumed non-pyramidal neurones located in the CA1 area of rat hippocampal slices. This excitatory effect persisted in conditions of synaptic uncoupling. In contrast, pyramidal neurones were either unaffected by neurohypophysial peptides or showed one or several of the following effects: a decrease in firing rate in cells which were spontaneously active; a slight membrane hyperpolarization; and an increase in the rate of occurrence of spontaneous inhibitory postsynaptic potentials. We therefore propose that oxytocin and vasopressin excite directly a class of non-pyramidal inhibitory interneurones, whereas their observed effect on pyramidal neurones is indirect and inhibitory.

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Stimulatory action of oxytocin on neurones of the dorsal motor nucleus of the vagus nerve.

Extracellular recordings were obtained from spontaneously active neurones located in the dorsal motor nucleus of vagus nerve ( DMX ) in slices of the rat brainstem. Oxytocin applied to the bath at concentrations of 10(-7) M or 10(-6) M excited 79% of these cells in a concentration-dependent, reversible manner. The remaining cells were unaffected. The stimulatory effect of oxytocin was reversibly antagonized by a synthetic structural analogue known to block the peripheral, endocrine effects of neurohypophysial peptides. A selective oxytocic agonist was as potent as oxytocin, whereas vasopressin exerted a much weaker effect. We therefore suggest that neurones located in DMX are endowed with receptors for oxytocin.

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Characterization of a uterine-type oxytocin receptor in the rat hippocampus.

Extracellular recordings were obtained from a class of nonpyramidal neurones in hippocampal slices. Oxytocin applied to the bath at concentrations of 1 nM or greater excited these cells. This effect was reversibly antagonized by a synthetic structural analogue known to block the peripheral endocrine effects of oxytocin. The effect of oxytocin was mimicked by a selective oxytocic agonist and, with less potency, by vasopressin and by other structural analogues. The potencies of oxytocin, vasopressin, and of these analogues in the hippocampus correlated well with their uterotonic activities but not with their vasopressor or antidiuretic activities. The data suggest that a class of hippocampal neurones is endowed with receptors for oxytocin that are similar to those of uterine smooth muscle cells.

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Paraventricular neurones in the rat hypothalamic slice: Lucifer Yellow injection and immunocytochemical identification.

Intracellular records were obtained from paraventricular neurones injected with Lucifer Yellow in slices from the rat hypothalamus. Slices containing fluorescent neurones were then serially cut and alternating sections were stained immunocytochemically for vasopressin or oxytocin. Double-labelled cells were found which fluoresced and which had reacted with either vasopressin or oxytocin antiserum.

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