Lab of Systems Neuroscience, Institute for Neuroscience, Department of Health Science and Technology, Swiss Federal Institute of Technology ETH, Zurich, Switzerland.
Institute for Physiological Chemistry, Biochemical-Pharmacological Center Marburg, Philipps-University of Marburg, Marburg, Germany.
Elife. 2022 Mar 15;11:e74056. doi: 10.7554/eLife.74056.
The proper development and function of neuronal circuits rely on a tightly regulated balance between excitatory and inhibitory (E/I) synaptic transmission, and disrupting this balance can cause neurodevelopmental disorders, for example, schizophrenia. MicroRNA-dependent gene regulation in pyramidal neurons is important for excitatory synaptic function and cognition, but its role in inhibitory interneurons is poorly understood. Here, we identify as a regulator of short-term memory and inhibitory synaptic transmission in the mouse hippocampus. Sponge-mediated inactivation specifically in mouse parvalbumin (PV)-expressing interneurons impairs spatial recognition memory and enhances GABAergic synaptic input onto pyramidal neurons. Cellular and behavioral phenotypes associated with inactivation are paralleled by an upregulation of the schizophrenia (SCZ)-associated , which we validated as a direct target gene. Our findings suggest that is a critical regulator of PV interneuron function in mice, with implications for cognition and SCZ. More generally, they provide evidence that microRNAs orchestrate neural circuit development by fine-tuning both excitatory and inhibitory synaptic transmission.
神经元回路的正常发育和功能依赖于兴奋性和抑制性（E/I）突触传递之间的严格调节平衡，破坏这种平衡会导致神经发育障碍，例如精神分裂症。在锥体神经元中，microRNA 依赖性基因调控对于兴奋性突触功能和认知很重要，但在抑制性中间神经元中的作用却知之甚少。在这里，我们确定 是小鼠海马体中短期记忆和抑制性突触传递的调节因子。海绵体介导的特异性在小鼠表达钙结合蛋白 parvalbumin（PV）的中间神经元中的失活会损害空间识别记忆并增强 GABA 能突触输入到锥体神经元上。与 失活相关的细胞和行为表型与精神分裂症（SCZ）相关的 上调相平行，我们验证了其作为直接 靶基因。我们的研究结果表明， 是小鼠中 PV 中间神经元功能的关键调节因子，对认知和 SCZ 具有重要意义。更广泛地说，它们提供了证据表明 microRNAs 通过微调兴奋性和抑制性突触传递来协调神经回路的发育。
