Autism spectrum disorder is a heterogeneous neurodevelopmental disorder characterized by impaired social interactions, restricted, and stereotyped behaviors. The valproic acid model is one of the most recognized and broadly used models in rats to induce core symptoms of this disorder. Comorbidity of epilepsy and autism occurs frequently, due to similar background mechanisms that include the imbalance of excitation and inhibition. In this series of experiments, treatment was performed on rat dams with a single 500 mg/kg dose i.p. valproate injection on embryonic day 12.5. Intracellular whole-cell patch clamp recordings were performed on brain slices prepared from adolescent and adult offspring of both sexes on pyramidal neurons of the medial prefrontal cortex and entorhinal cortex. Current clamp stimulation utilizing conventional current step protocols and dynamic clamp stimulation were applied to assess neuronal excitability. Membrane properties and spiking characteristics of layer II–III pyramidal cells were analyzed in both cortical regions. Significant sex-dependent and age-dependent differences were found in several parameters in the control groups. Considering membrane resistance, rheobase, voltage sag slope, and afterdepolarization slope, we observed notable changes mainly in the female groups. Valproate treatment seemed to enhance these differences and increase network excitability. However, it is possible that compensatory mechanisms took place during the maturation of the network while reaching the age-group of 3 months. Based on the results, the expression of the hyperpolarization-activated cyclic nucleotide-gated channels may be appreciably affected by the valproate treatment, which influences fundamental electrophysiological properties of the neurons such as the voltage sag. Remarkable changes appeared in the prefrontal cortex; however, also the entorhinal cortex shows similar tendencies.

中文翻译：

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根据膜片钳研究，丙戊酸治疗可诱导年龄和性别依赖性神经元活动变化

自闭症谱系障碍是一种异质性神经发育障碍，其特征是社交互动受损、行为受限和刻板。丙戊酸模型是最受认可和广泛使用的大鼠模型之一，可诱导这种疾病的核心症状。由于相似的背景机制，包括兴奋和抑制的不平衡，癫痫和自闭症的合并症经常发生。在这一系列实验中，在胚胎第12.5天对大鼠进行单次500 mg/kg剂量的丙戊酸腹膜内注射治疗。对取自青少年和成年男女后代的内侧前额皮质和内嗅皮质锥体神经元的脑切片进行细胞内全细胞膜片钳记录。利用传统电流步进方案和动态钳刺激的电流钳刺激来评估神经元兴奋性。对两个皮质区域的 II-III 层锥体细胞的膜特性和尖峰特征进行了分析。对照组的几个参数存在显着的性别依赖性和年龄依赖性差异。考虑到膜电阻、流变碱、电压暂降斜率和后除极斜率，我们主要在女性组中观察到显着的变化。丙戊酸治疗似乎增强了这些差异并增加了网络兴奋性。然而，补偿机制可能是在网络成熟期间达到 3 个月年龄组时发生的。根据结果​​，超极化激活的环核苷酸门控通道的表达可能会明显受到丙戊酸治疗的影响，这会影响神经元的基本电生理特性，例如电压骤降。前额皮质出现了显着的变化；然而，内嗅皮层也表现出类似的趋势。