Beitchman Joshua A, Krishna Gokul, Bromberg Caitlin E, Thomas Theresa Currier
BARROW Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA.
Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA.
bioRxiv. 2023 Feb 16:2023.02.16.528856. doi: 10.1101/2023.02.16.528856.
Aspects of glutamate neurotransmission implicated in normal and pathological conditions are often evaluated using recording paradigms in rats anesthetized with isoflurane or urethane. Urethane and isoflurane anesthesia influence glutamate neurotransmission through different mechanisms; however real-time outcome measures of potassium chloride (KCl)-evoked glutamate overflow and glutamate clearance kinetics have not been compared within and between regions of the brain. In the following experiments, amperometric recordings of KCl-evoked glutamate overflow and glutamate clearance kinetics (uptake rate and T) in the cortex, hippocampus and thalamus were performed using glutamate-selective microelectrode arrays (MEAs) in young adult male, Sprague-Dawley rats anesthetized with isoflurane or urethane. Potassium chloride (KCl)-evoked glutamate overflow was similar under urethane and isoflurane anesthesia in all brain regions studied. Analysis of glutamate clearance determined that the uptake rate was significantly faster (53.2%, p<0.05) within the thalamus under urethane compared to isoflurane, but no differences were measured in the cortex or hippocampus. Under urethane, glutamate clearance parameters were region dependent, with significantly faster glutamate clearance in the thalamus compared to the cortex but not the hippocampus (p<0.05). No region dependent differences were measured for glutamate overflow using isoflurane. These data support that amperometric recordings of glutamate under isoflurane and urethane anesthesia result in mostly similar and comparable data. However, certain parameters of glutamate uptake vary based on choice of anesthesia and brain region. Special considerations must be given to these areas when considering comparison to previous literature and when planning future experiments.
在正常和病理条件下，谷氨酸神经传递的相关方面通常使用异氟烷或氨基甲酸乙酯麻醉的大鼠记录范式进行评估。氨基甲酸乙酯和异氟烷麻醉通过不同机制影响谷氨酸神经传递；然而，尚未在脑区内和脑区之间比较氯化钾（KCl）诱发的谷氨酸溢出和谷氨酸清除动力学的实时结果测量。在以下实验中，使用谷氨酸选择性微电极阵列（MEA）对用异氟烷或氨基甲酸乙酯麻醉的成年雄性Sprague-Dawley大鼠的皮质、海马体和丘脑进行KCl诱发的谷氨酸溢出和谷氨酸清除动力学（摄取率和T）的安培记录。在所有研究的脑区中，氨基甲酸乙酯和异氟烷麻醉下KCl诱发的谷氨酸溢出相似。谷氨酸清除分析确定，与异氟烷相比，氨基甲酸乙酯麻醉下丘脑内的摄取率明显更快（53.2%，p<0.05），但在皮质或海马体中未测量到差异。在氨基甲酸乙酯麻醉下，谷氨酸清除参数具有区域依赖性，丘脑内的谷氨酸清除明显快于皮质，但快于海马体（p<0.05）。使用异氟烷时，未测量到谷氨酸溢出的区域依赖性差异。这些数据支持在异氟烷和氨基甲酸乙酯麻醉下谷氨酸的安培记录产生的结果大多相似且具有可比性。然而，谷氨酸摄取的某些参数因麻醉选择和脑区而异。在与先前文献进行比较以及规划未来实验时，必须特别考虑这些方面。
