Curto Yasmina, Garcia-Mompo Clara, Bueno-Fernandez Clara, Nacher Juan
Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Dpt., Universitat de València, Spain.
Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Dpt., Universitat de València, Spain; CIBERSAM: Spanish National Network for Research in Mental Health, Spain; Fundación Investigación Hospital Clínico de Valencia, INCLIVA, Spain.
Neurosci Lett. 2016 Feb 2;613:41-6. doi: 10.1016/j.neulet.2015.12.048. Epub 2015 Dec 28.
The adult brain retains a substantial capacity for synaptic reorganization, which includes a wide range of modifications from molecular to structural plasticity. Previous reports have demonstrated that the structural remodeling of excitatory neurons seems to occur in parallel to changes in GABAergic neurotransmission. The function of neuronal inhibitory networks can be modified through GABAA receptors, which have a binding site for benzodiazepines (BZ). Although BZs are among the most prescribed drugs, is not known whether they modify the structure and connectivity of pyramidal neurons. In the present study we wish to elucidate the impact of a chronic treatment of 21 days with diazepam (2mg/kg, ip), a BZ that acts as an agonist of GABAA receptors, on the structural plasticity of pyramidal neurons in the prefrontal cortex of adult mice. We have examined the density of dendritic spines and the density of axonal en passant boutons in the cingulate cortex. Although no significant changes were observed in their anxiety levels, animals treated with diazepam showed a decrease in the density of spines in the apical dendrites of pyramidal neurons. Most GFP-expressing en passant boutons in the upper layers of the cingulate cortex had an extracortical origin and no changes in their density were detected after diazepam treatment. These results indicate that the chronic potentiation of GABAergic synapses can induce the structural remodeling of postsynaptic elements in pyramidal neurons.
成年大脑保留了相当大的突触重组能力，这包括从分子可塑性到结构可塑性的广泛修饰。先前的报告表明，兴奋性神经元的结构重塑似乎与GABA能神经传递的变化同时发生。神经元抑制网络的功能可通过GABAA受体进行调节，该受体具有苯二氮䓬（BZ）的结合位点。尽管BZ是最常用的处方药之一，但尚不清楚它们是否会改变锥体神经元的结构和连接性。在本研究中，我们希望阐明用作为GABAA受体激动剂的BZ地西泮（2mg/kg，腹腔注射）进行21天的慢性治疗对成年小鼠前额叶皮质锥体神经元结构可塑性的影响。我们检查了扣带回皮质中树突棘的密度和轴突旁结的密度。尽管在焦虑水平上未观察到显著变化，但用了地西泮治疗的动物在锥体神经元顶树突中的棘密度降低。扣带回皮质上层中大多数表达绿色荧光蛋白（GFP）的轴突旁结起源于皮质外，地西泮治疗后其密度未检测到变化。这些结果表明，GABA能突触的慢性增强可诱导锥体神经元中突触后元件的结构重塑。
