The Effects Of General Anesthetics On Glia Synaptic Regulation In Lateral Prefrontal Cortex Of Rats

Objective and background: Different general anesthetic has different target,but can all induce unconsciousness, the underlining specific mechanism is still not clear. The prefrontal cortex has the function of forming consciousness by-integrating information, and the lateral prefrontal cortex is associated with response inhibition,the function is mainly result from the interconnection between neurons. However, recently evidences suggested that astrocytescan release a variety of neurotransmitters and change the synapses slow inward currents(SICs), which willadmit the synaptic transmission.This experiment using the brain slice patchclamp technique to observe different general anesthetics on synaptic regulationof prefrontal cortex astrocytes(SICs asindicator) and determine whether astrocyte contribute to the general anesthesia unconsciousness process,provide new way for the research of mechanism of general anesthesia.Methods:Thelateralprefrontal cortex slices were prepared from healthy male SD rats(aged 21-28 postnatal days). The vitro slices from prefrontal was used to record SICs of pyramidal Neurons.The experiment was divided into four parts:1. Built whole cell recording mode, record SICs under voltage mode. Perfuse ACSF containing TTX(1μM) and fluorocitrate(5μM,astrocytes metabolic inhibitors)to prove astrocytes generate SICs; 2. The anesthetic intervention experiment, to perfuse with different ACSF,which containing propofol(10μM), ketamine(450μM), dexmedetomidine(1μM), observe their effects on SICs; 3. Drawing the concentration-effect curve of the effectiveanesthetic and calculating the concentration for 50% of maximal effect; 4. Utilaze the astrocyte specific toxin, L- alpha Aminoadipate(0.1m M) to analyze the relationship between the effects of anesthetic on SICs and glia glutamine release function.Results 1. Fluorocitrate significant inhibited the firingfrequency of SICs(P<0.05);2. Ketaminesignificant inhibited the firingfrequency of SICs(P<0.05), but exert no effects on the amplitude and decay time of SICs( P<0.05). Propofol and dexmedetomidine exert no effects on the frequency, amplitudeand decay time of SICs;3. Ketamine inhibited the firingfrequency of SICs in a concentration-dependent manner, the IC50 of ketamine was 562.4± 56.34 μM;4. LAAsignificantlydelay the decay timeof SICswith Ketamine perfusion.Conclusion 1. Thelateralprefrontal cortex astrocytes can regulate the SICs of synapses;2. Ketamine inhibitthe frequencyof SICs in a concentration-dependent manner and affect information transfer between astrocytes and pyramidal neurons, which will affect the synaptic transmission;3. Astrocytes may not participate in the effects of Propofol and Dexmedetomidineon the synaptic transmission;4. The inhibitory effects of Ketamineon the SICs may related to the glia glutamate release function.