Pérez-Rando Marta, Castillo-Gómez Esther, Bellés María, Carceller Héctor, Nácher Juan
Neurobiology Unit, Cell Biology Dpt., Interdisciplinary Research Structure for Biotechnology and Biomedicine (BIOTECMED), Universitat de València, Spain.
Neurobiology Unit, Cell Biology Dpt., Interdisciplinary Research Structure for Biotechnology and Biomedicine (BIOTECMED), Universitat de València, Spain; CIBERSAM: Spanish National Network for Research in Mental Health, Spain.
Neurosci Lett. 2017 Sep 29;658:79-84. doi: 10.1016/j.neulet.2017.08.042. Epub 2017 Aug 31.
N-Methyl-d-Aspartate receptors (NMDARs) are present in both pyramidal neurons and interneurons of the hippocampus. These receptors play a key role in the structural plasticity of excitatory neurons, but to date little is known about their influence on the remodeling of interneurons. Among hippocampal interneurons, the somatostatin expressing cells in the CA1 stratum oriens are of special interest because of their functional importance and structural characteristics: they display dendritic spines, which change their density in response to different stimuli. In order to understand the role of NMDAR activation on the structural dynamics of the spines of somatostatin expressing interneurons in the CA1 stratum oriens, we have studied entorhino-hippocampal organotypic cultures obtained from mice in which this interneuronal subpopulation expresses constitutively EGFP, and have imaged them in real-time. We have acutely infused the cultures with NMDA, a strong NMDAR agonist, and have analyzed the structural dynamics of somatostatin expressing interneurons, prior and after its administration. The appearance and disappearance rates of their dendritic spines increased 24h after the NMDA infusion and returned to baseline levels 48h afterwards. By contrast, their stability rate decreased 24h after the infusion and also returned to control levels 48h later. The relative density of the dendritic spines remained unaltered throughout the assay. Altogether, our results show that the activation of NMDARs can influence the structural dynamics of interneurons. This is especially important because of the involvement of these receptors in neuronal potentiation/depression and their putative role in the etiopathology of certain neuropsychiatric disorders, such as schizophrenia.
N-甲基-D-天冬氨酸受体（NMDARs）存在于海马体的锥体神经元和中间神经元中。这些受体在兴奋性神经元的结构可塑性中起关键作用，但迄今为止，关于它们对中间神经元重塑的影响知之甚少。在海马体中间神经元中，CA1 层 Oriens 中表达生长抑素的细胞因其功能重要性和结构特征而备受关注：它们具有树突棘，其密度会因不同刺激而改变。为了了解 NMDAR 激活对 CA1 层 Oriens 中表达生长抑素的中间神经元树突棘结构动力学的作用，我们研究了从神经元亚群组成性表达 EGFP 的小鼠中获得的内嗅-海马器官型培养物，并对其进行了实时成像。我们向培养物中急性注入了 NMDA（一种强效 NMDAR 激动剂），并分析了注入前后表达生长抑素的中间神经元的结构动力学。NMDA 注入后 24 小时，其树突棘的出现和消失率增加，48 小时后恢复到基线水平。相比之下，注入后 24 小时其稳定性率下降，48 小时后也恢复到对照水平。在整个实验过程中，树突棘的相对密度保持不变。总之，我们的结果表明 NMDARs 的激活可以影响中间神经元的结构动力学。这一点尤为重要，因为这些受体参与神经元的增强/抑制作用，并且在某些神经精神疾病（如精神分裂症）的病因学中可能发挥作用。
