Presynaptic GABAB receptors functionally uncouple somatostatin interneurons from the active hippocampal network

Information processing in cortical neuronal networks relies on properly balanced excitatory and inhibitory neurotransmission. A ubiquitous motif for maintaining this balance is the somatostatin interneuron (SOM-IN) feedback microcircuit. Here, we investigate the modulation of this microcircuit by presynaptic GABAB receptors (GABABRs) in the rat hippocampus. Whole-cell recordings from SOM-INs reveal that both excitatory and inhibitory synaptic inputs are strongly inhibited by GABABRs, while optogenetic activation of the interneurons shows that their inhibitory output is also strongly suppressed. Electron microscopic analysis of immunogold-labelled freeze-fracture replicas confirms that GABABRs are highly expressed presynaptically at both input and output synapses of SOM-INs. Activation of GABABRs selectively suppresses the recruitment of SOM-INs during gamma oscillations induced in vitro. Thus, axonal GABABRs are positioned to efficiently control the input and output synapses of SOM-INs and can functionally uncouple them from local network with implications for rhythmogenesis and the balance of entorhinal versus intrahippocampal afferents.

大脑皮层神经元网络的信息处理依赖于兴奋性与抑制性神经传递的精确平衡。维持该平衡的一类普遍存在的环路基序是生长抑素中间神经元（somatostatin interneuron, SOM-IN）反馈微环路。本研究以大鼠海马为实验对象，探究突触前GABAB受体（GABAB receptors, GABABRs）对该微环路的调控作用。对SOM-IN的全细胞膜片钳记录结果显示，GABABRs可强烈抑制其兴奋性与抑制性突触输入；而对中间神经元的光遗传激活实验表明，其抑制性输出同样被显著抑制。免疫金标记冷冻断裂复型样品的电镜分析证实，GABABRs在SOM-IN的输入与输出突触的突触前膜均呈现高表达。GABABRs的激活可在体外诱导的γ振荡过程中，选择性抑制SOM-IN的募集。综上，轴突GABABRs可有效调控SOM-IN的输入与输出突触，并能在功能上使SOM-IN与局部神经网络解耦，这对节律发生以及内嗅皮层与海马内传入纤维的平衡具有潜在影响。