Effects Of GABA_A Receptor Agonist-type Of Anaesthetics Propofol,Etomidate,Midazolam On The Spontaneous Oscillations In CA1 Of Intact Hippocampal Formation In Vitro

General anesthetics can induce patients and animals to lose of consciousness,perception,and feelings.It is generally believed that the effect of general anesthetics is closely related to the neural activity of the different brain areas.There have been many researches on the effect and mechanism of anesthetics on the whole brain activity.However,the neural mechanism needs to be further investigated.All the following work was conducted on complete hippocampus from young rats of 14-18postnatal days.We investigate the propofol,etomidate and midazolam these three kinds of GABA_A receptor agonist-type of anaesthetics on spontaneous oscillations in CA1 of intact hippocampal formation in vitro.Main findings are as follows:(1)Spontaneous oscillations in CA1 of intact hippocampal formation in vitro is low frequency range of 0.4~1.8 Hz,and the oscillation pattern and frequency are very stable,long sustainable.(2)The spontaneous oscillations in CA1 is inhibited by 6?M propofol,4?M etomidate and 10?M midazolam.6?M propofol can block almost all spontaneous oscillations in CA1.After the application of 4?M etomidate or 10?M midazolam,spontaneous oscillations in CA1 could not be completely inhibited.Moreover,the frequency and amplitude of hippocampal CA1 oscillation gradually recovered after washout,but it could not fully recover to the level of baseline within30 minutes.(3)After doubling the concentration of these three drugs,the inhibitory effect on hippocampal CA1 oscillations was enhanced with the increase of concentration,indicating that propofol,etomidate and midazolam had a dose-dependent effect on the inhibition of hippocampal CA1 spontaneous oscillation.(4)When reducing the concentration of propofol to 0.1?M,it was observed that spontaneous oscillations of hippocampal CA1 was significantly enhanced.Moreover,after the addition of GABA_A receptor blocker,the spontaneous oscillation of hippocampal CA1 induced by 0.1?M propofol could be reversed,indicating that the spontaneous oscillation of hippocampal CA1 induced by low concentration of propofol was dependent on the activity of GABA_A receptor.The findings suggest that GABA_A agonist-type of general anesthetics can influence the oscillations of brain circuits,and this provide new data for further understanding of the neural mechanism of GABA_A agonist-type of general anesthetics.