Isolation of the murine Glut1 deficient thalamocortical circuit: wavelet characterization and reverse glucose dependence of low and gamma frequency oscillations.
Isolation of the murine Glut1 deficient thalamocortical circuit: wavelet characterization and reverse glucose dependence of low and gamma frequency oscillations.
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小鼠 Glut1 缺陷丘脑皮质回路的分离：小波表征和低频率和伽马频率振荡的反向葡萄糖依赖性。
DOI：
10.1101/2023.06.05.543611
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Jakkamsetti,Vikram
中科院分区：
文献类型：
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作者：
Solis,ElysandraM;Good,LeviB;GranjaVázquez,Rafael;Patnaik,Sourav;Hernandez-Reynoso,AnaG;Ma,Qian;Angulo,Gustavo;Dobariya,Aksharkumar;Cogan,StuartF;Pancrazio,JosephJ;Pascual,JuanM;Jakkamsetti,Vikram
葡萄糖是大脑能量的主要来源。因此，不出所料，遗传性葡萄糖转运蛋白1 （Glut1）缺乏（G1D）表现为脑病。G1D癫痫发作是一种突出的疾病表现，通常对药物无效，但可能对治疗性饮食有反应。从人类脑电图和功能成像推断，这些癫痫发作与异常的丘脑皮质振荡有关。小鼠电生理记录表明，丘脑和皮层的抑制性神经元失效是这些异常的基础。这为开发一个神经回路测试平台提供了动力，以表征丘脑皮质同步的机制以及已知或新的干预措施的影响。为此，我们在多电极阵列上使用小鼠丘脑皮质切片，并在接近生理的沐浴葡萄糖浓度下表征自发低频振荡和频率较低的30-50 Hz或伽马振荡。利用第四层的皮质记录和其他区域的记录，我们用一种基于自动小波的算法量化了振荡的年代。该方法在分析上优于功率谱密度、短时傅立叶变换或幅度阈值检测。正如人体观察所预期的那样，增加的葡萄糖减少了低频振荡，同时增加了伽马振荡，可能反映了抑制性神经元活动的增强，从而降低了低频：高频比（LHR）。这种方法为评估关键G1D癫痫发生回路中的机制、燃料和药理学试剂提供了一种活体方法。
Glucose represents the principal brain energy source. Thus, not unexpectedly, genetic glucose transporter 1 (Glut1) deficiency (G1D) manifests with encephalopathy. G1D seizures, which constitute a prominent disease manifestation, often prove refractory to medications but may respond to therapeutic diets. These seizures are associated with aberrant thalamocortical oscillations as inferred from human electroencephalography and functional imaging. Mouse electrophysiological recordings indicate that inhibitory neuron failure in thalamus and cortex underlies these abnormalities. This provides the motivation to develop a neural circuit testbed to characterize the mechanisms of thalamocortical synchronization and the effects of known or novel interventions. To this end, we used mouse thalamocortical slices on multielectrode arrays and characterized spontaneous low frequency oscillations and less frequent 30–50 Hz or gamma oscillations under near-physiological bath glucose concentration. Using the cortical recordings from layer IV among other regions recorded, we quantified oscillation epochsviaan automated wavelet-based algorithm. This method proved analytically superior to power spectral density, short-time Fourier transform or amplitude-threshold detection. As expected from human observations, increased bath glucose reduced the lower frequency oscillations while augmenting the gamma oscillations, likely reflecting strengthened inhibitory neuron activity, and thus decreasing the low:high frequency ratio (LHR). This approach provides anex vivomethod for the evaluation of mechanisms, fuels, and pharmacological agents in a crucial G1D epileptogenic circuit.