scholarly journals Non-linear GABAA receptors promote synaptic inhibition in developing neurons

Author(s):  
Knut Kirmse
2004 ◽  
Vol 101 (1) ◽  
pp. 66-74 ◽  
Author(s):  
Misha Perouansky ◽  
Robert A. Pearce

Background Although it does not suppress movement in response to noxious stimuli, the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, also known as 2N) does cause amnesia and seizures. These occur at 0.48 and 1.3 times, respectively, the concentrations that are predicted from its lipid solubility to cause immobility. The molecular and cellular basis of these effects is not known. The ionotropic gamma-aminobutyric acid type A (GABAA) receptor is modulated strongly by anesthetics, and it plays an important role in many seizure models. Also, the hippocampus is a structure central to the formation of memory and is susceptible to seizure generation. The authors therefore investigated the effect of F6 on GABAA receptor- mediated inhibition in hippocampal neurons. Methods Transverse hippocampal slices were prepared from young (12- to 21-day-old) Sprague-Dawley rats. Inhibitory postsynaptic currents were recorded from hippocampal CA1 pyramidal cells in the presence of ionotropic glutamate receptor antagonists. F6 was applied with the bath solution. The concentration of F6 achieved during the experiment at the location of synaptic inhibition was derived using a diffusion model. Results At tissue concentrations of up to 75 microm (approximately 5 x predicted minimal alveolar concentration), F6 had no discernible effect on either the amplitude or the kinetics of GABA-mediated synaptic currents. Isoflurane, by contrast, prolonged the decay time constant of these currents at 100 microm (approximately 0.3 x minimal alveolar concentration). Conclusions At concentrations that bracket the in vivo amnestic and seizure-inducing range, F6 has no discernible effect on fast synaptic GABAA receptors in hippocampal CA1 pyramidal neurons. Synaptic GABAA receptors sharply discriminate between volatile anesthetics and a prototype nonimmobilizer. Similar in vivo effects of anesthetics and nonimmobilizers may be mediated by different cellular mechanisms.


1967 ◽  
Vol 28 ◽  
pp. 105-176
Author(s):  
Robert F. Christy

(Ed. note: The custom in these Symposia has been to have a summary-introductory presentation which lasts about 1 to 1.5 hours, during which discussion from the floor is minor and usually directed at technical clarification. The remainder of the session is then devoted to discussion of the whole subject, oriented around the summary-introduction. The preceding session, I-A, at Nice, followed this pattern. Christy suggested that we might experiment in his presentation with a much more informal approach, allowing considerable discussion of the points raised in the summary-introduction during its presentation, with perhaps the entire morning spent in this way, reserving the afternoon session for discussion only. At Varenna, in the Fourth Symposium, several of the summaryintroductory papers presented from the astronomical viewpoint had been so full of concepts unfamiliar to a number of the aerodynamicists-physicists present, that a major part of the following discussion session had been devoted to simply clarifying concepts and then repeating a considerable amount of what had been summarized. So, always looking for alternatives which help to increase the understanding between the different disciplines by introducing clarification of concept as expeditiously as possible, we tried Christy's suggestion. Thus you will find the pattern of the following different from that in session I-A. I am much indebted to Christy for extensive collaboration in editing the resulting combined presentation and discussion. As always, however, I have taken upon myself the responsibility for the final editing, and so all shortcomings are on my head.)


Optimization ◽  
1975 ◽  
Vol 6 (4) ◽  
pp. 549-559
Author(s):  
L. Gerencsér

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