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A Khateb

Publications and source records attributed to A Khateb.

31 records · Page 2Linked to original sources
PubMed1995

Cholinergic nucleus basalis neurons are excited by histamine in vitro.

Considerable evidence has shown that both cholinergic and histaminergic neurons in the brain may act to facilitate processes of cortical activation that occur during wakefulness. In the present study, the potential influence of histaminergic neurons upon cholinergic neurons of the basal forebrain was investigated in guinea-pig basal forebrain slices. We found that electrophysiologically identified and immunohistochemically verified cholinergic neurons of the nucleus basalis were depolarized and excited by histamine, as manifested by an increase in tonic firing. The depolarization was associated with an increase in membrane input resistance. The effect of histamine persisted in the presence of either tetrodotoxin or a high-magnesium/low-calcium solution, indicating that it is postsynaptic. By a process of elimination, the participation in this response of the three described histamine receptors was examined. Involvement of H3 receptors was excluded on the basis that the H3 agonist (R)-alpha-methyl-histamine had no direct effect, and the H3 antagonist, thioperamide, did not block the effect of histamine. In contrast, the presence of a small response to impromidine, a selective agonist of H2 receptors, and the partial block of the response to histamine by the H2 receptor antagonist, cimetidine, indicated the participation of H2 receptors. Finally, the complete elimination of histamine's effect occurred when low doses of the H1 antagonist, mepyramine, were added to the H2 antagonist, cimetidine, indicating the involvement and predominance of H1 receptors in the response. Our data thus suggest that histamine excites nucleus basalis cholinergic neurons by a concomitant activation of H1 and H2 receptors. Histaminergic tuberomammillary neurons may accordingly facilitate tonic firing of cholinergic neurons during wakefulness. Cholinergic basalis neurons could thus act in tandem with histaminergic neurons during periods of arousal to collectively promote widespread cortical activation.

Action Potentials↗
PubMed1993

Pharmacological and immunohistochemical evidence for serotonergic modulation of cholinergic nucleus basalis neurons.

Identified electrophysiologically by low threshold bursts and transient outward rectification, cholinergic nucleus basalis neurons were recorded and labelled intracellularly in guinea-pig basal forebrain slices. By means of a triple labelling immunofluorescent technique, serotonin-immunoreactive fibres were visualized in close proximity to the soma and dendrites of the biocytin-labelled, choline acetyl transferase (ChAT)-immunoreactive cells. By bath application, 5-hydroxytryptamine (5-HT) produced a direct hyperpolarization of the identified cells which was mimicked by 5-HT1A receptor agonists, suggesting that it may inhibit the tonic firing but also modulate the low threshold bursting of the cholinergic nucleus basalis neurons.

Animals↗
PubMed1993

Medial vestibular nucleus in the guinea-pig: histaminergic receptors. I. An in vitro study.

Antihistaminergic drugs are currently used for the symptomatic treatment of vestibular-related syndromes such as vertigo and motion sickness. We therefore investigated whether histamine could modulate the firing of medial vestibular nuclei neurons (MVNn). Recently, we have demonstrated that different cell types are present among MVNn in guinea-pig brainstem slices. Bath-application of histamine at 10(-4) or 10(-5) M induced a small membrane depolarization accompanied by a slight decrease in membrane resistance and a reversible increase in spontaneous firing in all MVN cell types. These effects were presumably postsynaptic as they persisted in a low-calcium/high-magnesium solution. Using a variety of agonists and antagonists of histamine receptors (H1, H2 and H3), we conclude that these effects are mediated by H2 receptors. The companion paper is concerned with an in vivo study of the histaminergic modulation of the vestibular function (Yabe et al., in press).

Animals↗
PubMed1993

Medial vestibular nucleus in the guinea-pig: apamin-induced rhythmic burst firing--an in vitro and in vivo study.

In a previous in vitro study, we have shown that guinea-pig medial vestibular nucleus neurons (MVNn) can be grouped into two main cell types based on their intrinsic membrane properties. Subsequent in vivo and in vitro studies demonstrated that these neurons are endowed with N-methyl-D-aspartate (NMDA) receptors and that NMDA induces rhythmic bursts in B MVNn. We now report the occurrence of rhythmic bursts in B MVNn (and in the subclass of B+LTS MVNn) which are induced by long-lasting perfusion of either apamin, a selective blocker of one type of Ca(2+)-dependent K+ conductance (SK channels), or by a high Mg2+/low Ca2+ artificial cerebrospinal fluid. Apamin-induced bursts were studied in vitro in brainstem slices, and in vivo in the alert unrestrained guinea-pig. In vitro, intracellular recordings demonstrated that the frequency of the bursts was voltage dependent. These bursts were insensitive to D-2-amino-5-phosphopentanoic acid but could be abolished by tetrodotoxin or blocked by the bath application of 20-50 microM of ouabain, a blocker of the sodium pump. In the in vivo preparation, unilateral infusion of apamin into the vestibular nuclei induced oscillatory head and eye movements. Our data show that the blockade of a Ca(2+)-activated K+ conductance may switch, in vitro and probably in vivo, the B MVn firing pattern from a regular to a bursting firing pattern.

2-Amino-5-phosphonovalerate↗
PubMed1992

Medial vestibular nucleus in the guinea-pig: NMDA-induced oscillations.

We have recently shown in vivo that N-Methyl-D-Aspartate (NMDA) receptors are present in the guinea-pig vestibular complex and demonstrated that they are involved in the regulation of the resting discharge of vestibular neurones. A parallel in vitro study has identified in the guinea-pig medial vestibular nuclei (MVN) two main neuronal cell types, A and B MVNn, differing by their intrinsic membrane properties. One subtype of B MVNn was further characterized by the presence of a low threshold calcium spike (LTS). The present study investigated in vitro the responses of these different cell types to NMDA. Both A and B MVNn were depolarized by NMDA, which also induced a decrease in membrane resistance and an increase in the spontaneous firing rate. These effects could be blocked by D-AP5, a specific antagonist of NMDA receptors. Following a 10-30 mV hyperpolarization, a long-lasting oscillatory behavior could be induced in presence of NMDA. These oscillations were however restricted to the subtype of B MVNn without LTS. The NMDA-induced oscillations were tetrodotoxine-resistant, but could be eliminated by D-AP5 or by replacing sodium with choline. Functional implications of this oscillatory behavior are discussed.

2-Amino-5-phosphonovalerate↗
PubMed1992

Cholinergic nucleus basalis neurons display the capacity for rhythmic bursting activity mediated by low-threshold calcium spikes.

Acetylcholine has long been known to play an important role in the cortical activation that accompanies the states of wakefulness and paradoxical sleep (for review, see Refs 17, 21) when this neurotransmitter is released from the cerebral cortex at the highest rates. The major supply of acetylcholine to the cerebral cortex arises from the cholinergic neurons of Meynert's Basal-ganglion or nucleus basalis of the forebrain. Lying in the substantia innominata within the major ascending pathway from the brain stem reticular formation, magnocellular basalis neurons project upon the cerebral cortex as the important ventral, extrathalamic relay of the ascending reticular activating system. Although the cholinergic basalis nucleus neurons have been shown to be important for cortical activation, the precise manner in which they influence cortical activity has not as yet been elucidated, in part because the cholinergic cells of this nucleus have not been identified in electrophysiological studies. Using intracellular recording in guinea-pig brain slices, we were able to record and fill with biocytin nucleus basalis neurons which were subsequently revealed by immunohistochemical staining to be choline acetyltransferase-positive and thus cholinergic. The cholinergic cells displayed rhythmic bursting activity mediated by a low-threshold calcium spike in vitro, which would endow them with a capacity for phasic (in addition to tonic) firing in vivo. By virtue of these different modes, cholinergic basalis neurons may accordingly deter or facilitate the cortical response to sensory input and may furthermore modulate the major frequencies of cortical activity across the different states of the sleep-waking cycle.

Animals↗
PubMed1991

Medial vestibular nucleus in the guinea-pig. I. Intrinsic membrane properties in brainstem slices.

Intracellular recordings were obtained from medial vestibular nuclei neurones (MVNn) in guinea-pig brainstem slices. Two main distinct neuronal classes were encountered. Type A MVNn (32.3%) were characterized by a broad action potential followed by a deep single afterhyperpolarization, a transient A-like rectification, and a single range of firing in response to current injection. Type B MVNn (47.1%), in contrast, were distinguished by the presence of a thin action potential followed first by a fast and then by a delayed and slower afterhyperpolarization. In addition, they displayed a secondary range of firing in their response to current injection. A majority of B MVNn also had either sub-threshold plateau potentials or low threshold spike bursts or a combination thereof. A third, non-homogeneous class of cells, could not be fitted into either one of the two main classes (20.6%, type C MVNn).

Action Potentials↗
PubMed1991

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↗
PubMed1990

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.

Action Potentials↗
PubMed1990

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.

Animals↗
PubMed1990

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↗
PubMed1990

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.

Action Potentials↗