Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio , San Antonio, Texas.
Xiangya School of Medicine, Central South University , Changsha, Hunan , China.
J Neurophysiol. 2019 May 1;121(5):1896-1905. doi: 10.1152/jn.00779.2018. Epub 2019 Mar 20.
Many synapses, including parallel fiber synapses in the cerebellum, express presynaptic GABA receptors. However, reports of the functional consequences of presynaptic GABA receptor activation are variable across synapses, from inhibition to enhancement of transmitter release. We find that presynaptic GABA receptor function is bidirectional at parallel fiber synapses depending on GABA concentration and modulation of GABA receptors in mice. Activation of GABA receptors by low GABA concentrations enhances glutamate release, whereas activation of receptors by higher GABA concentrations inhibits release. Furthermore, blocking GABA receptors reduces GABA receptor currents and shifts presynaptic responses toward greater enhancement of release across a wide range of GABA concentrations. Conversely, enhancing GABA receptor currents with ethanol or neurosteroids shifts responses toward greater inhibition of release. The ability of presynaptic GABA receptors to enhance or inhibit transmitter release at the same synapse depending on activity level provides a new mechanism for fine control of synaptic transmission by GABA and may explain conflicting reports of presynaptic GABA receptor function across synapses. GABA receptors are widely expressed at presynaptic terminals in the central nervous system. However, previous reports have produced conflicting results on the function of these receptors at different synapses. We show that presynaptic GABA receptor function is strongly dependent on the level of receptor activation. Low levels of receptor activation enhance transmitter release, whereas higher levels of activation inhibit release at the same synapses. This provides a novel mechanism by which presynaptic GABA receptors fine-tune synaptic transmission.
许多突触，包括小脑的平行纤维突触，都表达了突触前 GABA 受体。然而，突触前 GABA 受体激活的功能后果在不同的突触之间是多变的，从抑制到增强递质释放。我们发现，在取决于 GABA 浓度和 GABA 受体调节的小鼠中，平行纤维突触的突触前 GABA 受体功能是双向的。低 GABA 浓度下 GABA 受体的激活增强谷氨酸释放，而较高 GABA 浓度下受体的激活抑制释放。此外，阻断 GABA 受体可减少 GABA 受体电流，并使突触前反应在广泛的 GABA 浓度范围内更偏向于增强释放。相反，用乙醇或神经甾体增强 GABA 受体电流会使反应更偏向于更大程度地抑制释放。同一突触上 GABA 受体根据活动水平增强或抑制递质释放的能力为 GABA 对突触传递的精细控制提供了一种新的机制，并可能解释 GABA 受体在不同突触上的功能的相互矛盾的报告。 GABA 受体在中枢神经系统的突触前末梢广泛表达。然而，之前的报告在这些受体在不同突触上的功能上产生了相互矛盾的结果。我们表明，突触前 GABA 受体的功能强烈依赖于受体激活的水平。低水平的受体激活增强递质释放，而更高水平的激活在同一突触上抑制释放。这为突触前 GABA 受体微调突触传递提供了一种新的机制。
