Laboratory of Neuronal Signaling, Department of Neuroscience and Pharmacology, University of Copenhagen Copenhagen, Denmark.
Front Neural Circuits. 2014 Jun 4;8:60. doi: 10.3389/fncir.2014.00060. eCollection 2014.
Spinal neuronal networks are essential for motor function. They are involved in the integration of sensory inputs and the generation of rhythmic motor outputs. They continuously adapt their activity to the internal state of the organism and to the environment. This plasticity can be provided by different neuromodulators. These substances are usually thought of being released by dedicated neurons. However, in other networks from the central nervous system synaptic transmission is also modulated by transmitters released from astrocytes. The star-shaped glial cell responds to neurotransmitters by releasing gliotransmitters, which in turn modulate synaptic transmission. Here we investigated if astrocytes present in the ventral horn of the spinal cord modulate synaptic transmission. We evoked synaptic inputs in ventral horn neurons recorded in a slice preparation from the spinal cord of neonatal mice. Neurons responded to electrical stimulation by monosynaptic EPSCs (excitatory monosynaptic postsynaptic currents). We used mice expressing the enhanced green fluorescent protein under the promoter of the glial fibrillary acidic protein to identify astrocytes. Chelating calcium with BAPTA in a single neighboring astrocyte increased the amplitude of synaptic currents. In contrast, when we selectively stimulated astrocytes by activating PAR-1 receptors with the peptide TFLLR, the amplitude of EPSCs evoked by a paired stimulation protocol was reduced. The paired-pulse ratio was increased, suggesting an inhibition occurring at the presynaptic side of synapses. In the presence of blockers for extracellular ectonucleotidases, TFLLR did not induce presynaptic inhibition. Puffing adenosine reproduced the effect of TFLLR and blocking adenosine A1 receptors with 8-Cyclopentyl-1,3-dipropylxanthine prevented it. Altogether our results show that ventral horn astrocytes are responsible for a tonic and a phasic inhibition of excitatory synaptic transmission by releasing ATP, which gets converted into adenosine that binds to inhibitory presynaptic A1 receptors.
脊髓神经元网络对于运动功能至关重要。它们参与感觉输入的整合和节律性运动输出的产生。它们不断地使自身的活动适应机体的内部状态和环境。这种可塑性可以由不同的神经调质提供。这些物质通常被认为是由专门的神经元释放的。然而，在中枢神经系统的其他网络中，突触传递也可以被星形胶质细胞释放的递质所调制。星形胶质细胞对神经递质作出反应，释放出神经胶质递质，从而反过来调节突触传递。在这里，我们研究了脊髓腹角中的星形胶质细胞是否调节突触传递。我们在从新生小鼠脊髓切片制备中记录的腹角神经元中诱发突触输入。神经元对电刺激的反应是通过单突触 EPSC（兴奋性单突触突触后电流）来实现的。我们使用在胶质纤维酸性蛋白启动子下表达增强型绿色荧光蛋白的小鼠来识别星形胶质细胞。在单个相邻星形胶质细胞中螯合钙会增加突触电流的幅度。相比之下，当我们通过用肽 TFLLR 激活 PAR-1 受体来选择性地刺激星形胶质细胞时，由成对刺激方案诱发的 EPSC 的幅度减小。成对脉冲比增加，表明突触前抑制发生在突触的突触前侧。在存在细胞外核苷酸酶的阻断剂的情况下，TFLLR 不会诱导突触前抑制。腺苷的脉冲模拟了 TFLLR 的作用，而用 8-环戊基-1,3-二丙基黄嘌呤阻断腺苷 A1 受体则阻止了它。总的来说，我们的结果表明，腹角星形胶质细胞通过释放 ATP 来负责兴奋性突触传递的紧张性和阶段性抑制，ATP 转化为腺苷，与抑制性突触前 A1 受体结合。
