The excitation and depression of spinal neurones by ibotenic acid.

Curtis, D. R.; Lodge, David; McLennan, H.

doi:10.1113/jphysiol.1979.sp012796

Cited by 65 publications

(25 citation statements)

References 16 publications

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“…In the present study, we have not ob served any potentiation by kainate (or ibotenate) of the ex citatory actions of glutamate, aspartate, or homocysteate on medial hypothalamic neurons. While our observations con trast with earlier reports in the cerebral cortex [46], they are in agreement with more recent data that indicate different receptors for kainate and glutamate [50] and the possibility for a presynaptic rather than a postsynaptic interaction [II, 18,44], Ibotenate's actions on hypothalamic neurons are biphasic and thus resemble those reported on spinal cord [9,21,28] and cerebral cortical neurons [37]. The initial excitatory effects appear to be independent of the actions of glutam ate, but are followed by a prolonged depression of both spontaneous and glutamate-evoked activity ( fig.…”

Section: Discussionsupporting

confidence: 82%

“…The initial excitatory effects appear to be independent of the actions of glutam ate, but are followed by a prolonged depression of both spontaneous and glutamate-evoked activity ( fig. 5, 6), most likely due to the chemical or enzymatic conversion of ibot enate to muscimol or a related compound with actions simi lar to GABA [9], Esterification of glutamate and kainate to form GDEE and KDEE, respectively, has yielded substances that are re ported to antagonize amino acid and to a lesser extent syn aptic excitations [14,16,23,33]. In the hypothalamus, GDEE and KDEE were observed to alter both glutamateand aspartate-evoked responses non-selectively and are, therefore, viewed to have limited use as a means to differen tiate between these two putative transmitters.…”

Section: Discussionmentioning

confidence: 99%

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Actions of Acidic Amino Acids on the Excitability of Medial Hypothalamic Neurons in the Rat

Arnauld¹,

Layton²,

Padjen³

et al. 1983

Neuroendocrinology

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Systemic administration of acidic amino acids produces selective neurotoxic effects on neurons in the arcuate nucleus. However, little is known on the comparative or topographical actions of various acidic amino acids within the hypothalamus. In the present study, microiontophoretic methods were utilized to compare the sensitivity of arcuate nucleus neurons with other medial hypothalamic neurons during applications of glutamate, aspartate, homocysteate, and two conformationally restricted glutamate analogs, kainate and ibotenate. An increase in excitability to all test substances was observed from the majority of 62 neurons identified both as to location (arcuate, ventromedial and dorsomedial nuclei, and periventricular area) and to response to electrical stimulation in the median eminence, amygdala, and posterior pituitary. There was little difference in the sensitivity of neurons to glutamate, aspartate, or homocysteate. In contrast, kainate produced a more prominent and long-lasting excitation at lower application currents, frequently leading to spike inactivation and excessive depolarization followed by a prolonged recovery period. Ibotenate was also a potent excitatory agent, but its actions were biphasic, with an initial excitation followed by a decrease in excitability that influenced both spontaneous and glutamate-evoked firing; the latter is considered due to conversion of ibotenate to muscimol, a GABA analog. These observations suggest a homogeneity among arcuate and other medial hypothalamic neurons in terms of their membrane receptors and sensitivity to all acidic amino acids tested. Since acidic amino acids are also viewed as possible excitatory neurotransmitters within the hypothalamus, the diethyl esters of glutamic acid (GDEE) and kainic acid (KDEE), two proposed glutamate antagonists, were applied by microiontophoresis and assessed for their ability to alter glutamate- and aspartate-evoked activations and synaptically evoked excitations. Each agent depressed both glutamate- and aspartate-evoked activity nonselectively; thus, while they do affect acidic amino acid actions, they appear to be of limited use in differentiating between glutamate- and aspartate-activated receptors on medial hypothalamic neurons. Neither GDEE nor KDEE altered synaptically evoked excitations from the median eminence, amygdala, or posterior pituitary. Owing to the extensive dendritic arborization of hypothalamic neurons, it is possible that these agents attained a low potency at active synaptic sites. We suggest that further evaluations of the role of acidic amino acids as medial hypothalamic neurotransmitters include in vitro testing where it is possible to achieve a uniform application of their antagonists in known concentrations.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Actions of Acidic Amino Acids on the Excitability of Medial Hypothalamic Neurons in the Rat

Arnauld¹,

Layton²,

Padjen³

et al. 1983

Neuroendocrinology

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“…The most useful excitotoxins for func- tional investigations in the PPTg were shown to be quino-ibotenic acid killed all neurons in the nucleus without linic and ibotenic acids: 24 nmol quinolinate made relatively neurochemical preference, and yet both excitotoxins proselective lesions of cholinergic neurons, whereas 24 nmol duced circumscribed lesions (Rugg et al, 1992). It is particularly interesting that both of these excitotoxins are known to have their effects at least partly through NMDA rather than AMPA or kainate receptors (Curtis et al, 1979;Stone and Connick, 1985). Indeed, this point is emphasized by the fact that NMDA itself induces a similar profile of damage to ibotenate (but kills slightly fewer cholinergic neurons), whereas AMPA and kainate make very diffuse, nonselective lesions.…”

Section: Relationship To the Actions Of Excitotoxins In The Mesopontimentioning

confidence: 97%

Colocalization of ionotropic glutamate receptor subunits with NADPH-diaphorase-containing neurons in the rat mesopontine tegmentum

Inglis

Semba

1996

J. Comp. Neurol.

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Tegmental cholinergic neurons vary their discharge patterns across the sleep-wake cycle, and glutamate is suggested to play an important role in determining these firing patterns. Cholinergic and noncholinergic neurons in the mesopontine tegmentum have different susceptibilities to various excitotoxins, presumably because of heterogeneity in the expression of glutamate receptor subtypes in this area. By using a double-labeling procedure that combines nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) histochemistry and avidin-biotin-peroxidase immunocytochemistry with diaminobenzidine as the chromogen, we compared the colocalization of AMPA receptor subunits GluR1, GluR2/3, and GluR4, kainate receptor subunits GluR5/6/7, and an NMDA receptor subunit NMDAR1 on NADPH-diaphorase-positive (cholinergic) neurons in the mesopontine tegmentum. Throughout the brainstem, neurons immunoreactive for GluR2/3 and NMDAR1 were most numerous, whereas neurons labeled for GluR1, GluR4, and GluR5/6/7 were less common. Specifically within the mesopontine tegmentum, the proportion of double-labeled neurons in the diaphorase-containing cell population was highest with GluR1 (43%) and lowest with GluR5/6/7 (12%). Regardless of the receptor subunit type, the greatest numbers of double-labeled neurons were observed in the pedunculopontine tegmental nucleus pars compacta and the fewest in the dorsal aspect of the laterodorsal tegmental nucleus. In addition, there were regional differences in the relative expression of receptor subunits and diaphorase-positive neurons across the subdivisions of the tegmental cholinergic column. Because each ionotropic subunit confers distinctive properties to a receptor channel, the present results suggest that mesopontine cholinergic neurons have nonuniform responses to glutamate and are also discriminable from basal forebrain cholinergic neurons in terms of glutamate receptor configuration.

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“…The activation of GABA channels by anaesthetic agents whose chemical structures vary widely and are not easily reconciled with the classical requirements for GABA agonists (Curtis & Watkins, 1960) is unusual for the agonist-gated channels studied to date. It will be interesting to determine precisely how these anaesthetics activate GABA channels, and whether this occurs by interactions at the receptor site, or if the ionophore is opened directly.…”

Section: Halothane Ketamine and Diazepammentioning

confidence: 99%

Actions of anaesthetics and avermectin on GABA_A chloride channels in mammalian dorsal root ganglion neurones

Robertson

1989

British J Pharmacology

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1 The y-aminobutyric acid (GABA)-mimetic actions of some anaesthetics and the antehelminthic avermectin B1a were examined on freshly isolated mammalian dorsal root ganglion (DRG) neurones by use of suction electrodes and a single electrode voltage clamp.2 Pentobarbitone (60yM-3mM), chloralose (600yM-1mM), etomidate (10-100 pM), alphaxalone (10-60pM) and avermectin (10-60pM) directly activated chloride channels in GABA-sensitive DRG neurones. The agonist action was sensitive to block by bicuculline and picrotoxinin. 3 Steady-state current-voltage (I-V) curves for the anaesthetics were either linear, or rectified in the opposite direction to steady-state I-V curves obtained with GABA. Current relaxations in response to voltage jumps were also of the opposite direction. An extra surge of current ('bounce') was commonly observed on washout of some of these agonists. 4 Pentobarbitone was ineffective as an agonist at alkali pH (10.4 and 9.4), but was approximately twice as effective at acid (5.4) than at normal (7.4) pH values. 5 These results suggest that some anaesthetics and avermectin are capable of 'blocking' GABA channels in addition to activating them.

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The excitation and depression of spinal neurones by ibotenic acid.

Cited by 65 publications

References 16 publications

Actions of Acidic Amino Acids on the Excitability of Medial Hypothalamic Neurons in the Rat

Actions of Acidic Amino Acids on the Excitability of Medial Hypothalamic Neurons in the Rat

Colocalization of ionotropic glutamate receptor subunits with NADPH-diaphorase-containing neurons in the rat mesopontine tegmentum

Actions of anaesthetics and avermectin on GABA_A chloride channels in mammalian dorsal root ganglion neurones

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The excitation and depression of spinal neurones by ibotenic acid.

Cited by 65 publications

References 16 publications

Actions of Acidic Amino Acids on the Excitability of Medial Hypothalamic Neurons in the Rat

Actions of Acidic Amino Acids on the Excitability of Medial Hypothalamic Neurons in the Rat

Colocalization of ionotropic glutamate receptor subunits with NADPH-diaphorase-containing neurons in the rat mesopontine tegmentum

Actions of anaesthetics and avermectin on GABAA chloride channels in mammalian dorsal root ganglion neurones

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Actions of anaesthetics and avermectin on GABA_A chloride channels in mammalian dorsal root ganglion neurones