胶质母细胞瘤的增长会影响周围神经元网络的结构和生理特性，改变金字塔形神经元的活动，进而促进肿瘤进展。因此，识别脑胶质母细胞瘤对金字塔形神经元的影响非常重要，因为它们是重要的治疗靶点。我们在小鼠枕叶皮层正交移植小鼠胶质母细胞瘤细胞后，长期监测了视觉诱发电位。我们利用激光显微切割技术分析了II-III层金字塔形神经元的分子特性，并通过局部场电位（LFP）记录评估了患有胶质母细胞瘤的动物相对于对照小鼠发生癫痫的倾向。我们确定了患有胶质母细胞瘤的小鼠的神经功能障碍的时间序列，并在基于视觉反应衰减的症状阶段上进行了鉴定。在那个时候点上，我们显微切割了II-III层金字塔形神经元，并评估了一系列与突触传递和神经兴奋性有关的基因的表达。与对照组相比，癌周围神经元的SNARE复合物基因SNAP-25和GABA-A受体的α1亚单位的表达量降低。在谷氨酸能（即AMPA或NMDA受体亚单位）标记中未检测到显著变化。通过给肿瘤患小鼠输送苯二氮平反向激动剂DMCM（甲基-6,7-二甲氧基-4-乙基-β-吡咯烷-3-羧酸酯）进一步降低了GABA-A信号，导致两种肿瘤患小鼠出现癫痫。这些研究揭示了肿瘤相邻区域的主要细胞发生的新的分子变化。这些变化可以治疗性地被靶向，以改善患者的生活质量。©作者2023年。由牛津大学出版社代表神经肿瘤学会出版。

Glioblastoma growth impacts on the structure and physiology of peritumoral neuronal networks, altering the activity of pyramidal neurons which drives further tumor progression. It is therefore of paramount importance to identify glioma-induced changes in pyramidal neurons, since they represent a key therapeutic target.We longitudinal monitored visual evoked potentials after the orthotopic implant of murine glioma cells into the mouse occipital cortex. With laser microdissection we analysed layer II-III pyramidal neurons molecular profile and with Local Field Potentials (LFP) recordings we evaluated the propensity to seizures in glioma-bearing animals with respect to control mice.We determine the time course of neuronal dysfunction of glioma-bearing mice and we identify a symptomatic stage, based on the decay of visual response. At that time point, we microdissect layer II-III pyramidal neurons and evaluate the expression of a panel of genes involved in synaptic transmission and neuronal excitability. Compared to the control group, peritumoral neurons show a decrease in the expression of the SNARE complex gene SNAP-25 and the alpha1 subunit of the GABA-A receptor. No significant changes are detected in glutamatergic (i.e., AMPA or NMDA receptor subunit) markers. Further reduction of GABA-A signalling by delivery of a benzodiazepine inverse agonist, DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) precipitates seizures in two mouse models of tumor-bearing mice.These studies reveal novel molecular changes that occur in the principal cells of the tumor-adjacent zone. These modifications may be therapeutically targeted to ameliorate patients' quality of life.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.