All-trans retinoic acid induces synaptopodin-dependent metaplasticity in mouse dentate granule cells

Previously we showed that the vitamin A metabolite all-trans retinoic acid (atRA) induces synaptic plasticity in acute brain slices prepared from the mouse and human neocortex (Lenz et al., 2021). Depending on the brain region studied, distinct effects of atRA on excitatory and inhibitory neurotransmission have been reported. Here, we used intraperitoneal injections of atRA (10 mg/kg) in adult C57BL/6J mice to study the effects of atRA on excitatory and inhibitory neurotransmission in the mouse fascia dentate – a brain region implicated in memory acquisition. No major changes in synaptic transmission were observed in the ventral hippocampus while a significant increase in both sEPSC frequencies and synapse numbers were evident in the dorsal hippocampus 6 hours after atRA administration. The intrinsic properties of hippocampal dentate granule cells were not significantly different and hippocampal transcriptome analysis revealed no essential neuronal changes upon atRA treatment. In light ...

此前我们已有研究证实，维生素A代谢物全反式维甲酸（all-trans retinoic acid, atRA）可在源自小鼠与人类新皮层的急性脑片中诱导突触可塑性（Lenz等，2021）。已有研究表明，根据所研究的脑区不同，atRA对兴奋性与抑制性神经传递可产生截然不同的调控效应。本研究中，我们对成年C57BL/6J小鼠予以10 mg/kg剂量的atRA腹腔注射，以探究atRA对小鼠齿状回——一个与记忆获取过程密切相关的脑区——的兴奋性与抑制性神经传递的影响。在atRA给药6小时后，腹侧海马的突触传递未观察到显著变化，而背侧海马的sEPSC频率与突触数量均显著升高。海马齿状回颗粒细胞的固有特性未出现显著差异，且海马转录组分析显示，atRA处理后神经元未发生显著的本质性改变。鉴于……