Tonically active inhibition selectively controls feedforward circuits in mouse barrel cortex
Tonically active inhibition selectively controls feedforward circuits in mouse barrel cortex
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DOI：
10.1152/jn.01360.2007
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发表时间：
2008-08-01
影响因子：
2.5
通讯作者：
Huntsman, Molly M.
中科院分区：
文献类型：
--
作者：
Krook-Magnuson, Esther I.;Li, Peijun;Huntsman, Molly M.
由突触外γ-氨基丁酸A型（GABA（A））受体介导的紧张性抑制是控制细胞兴奋性的强大传导。在整个CNS中，紧张性抑制在不同细胞类型中以不同程度表达。尽管皮质中间神经元多样性的丰富历史，但对大脑皮质不同类别细胞的紧张性抑制知之甚少。因此，我们研究了细胞类型的特异性和功能意义的紧张性抑制在第4层的小鼠体感桶皮质。原位杂交和免疫细胞化学显示，中度δ-亚基表达的桶结构。全细胞膜片钳记录还表明，可以在不同细胞类型中发现显著水平的紧张性抑制，细胞类型之间的抑制幅度存在差异。为了激活紧张性电流，我们使用了4，5，6，7-四氢异恶唑并[5，4-c]吡啶-3-醇（THIP，一种在含有δ亚基的GABA（A）受体上的超激动剂），其浓度不影响突触衰减动力学。THIP使抑制性细胞的基线保持电流（低阈值尖峰[LTS]，109 +/- 17 pA;快速尖峰[FS]，111 +/- 15 pA）比兴奋性细胞（39 +/- 10 pA; P < 0.001）产生更大的偏移。除了细胞类型之间的这些差异外，抑制细胞内也存在变异性。动作电位快的FS细胞有较大的基线偏移。由于FS细胞是已知的前馈抑制介质，我们测试了THIP诱导的强直性电导是否选择性地控制前馈电路。THIP的应用导致在一个兴奋性神经元的子集丘脑诱发的双突触反应的抑制性突触后电位的废除。这些数据表明，多个前馈回路可以区分的抑制控制突触前抑制神经元。
Tonic inhibition mediated by extrasynaptic gamma-aminobutyric acid type A (GABA(A)) receptors is a powerful conductance that controls cell excitability. Throughout the CNS, tonic inhibition is expressed at varying degrees across different cell types. Despite a rich history of cortical interneuron diversity, little is known about tonic inhibition in the different classes of cells in the cerebral cortex. We therefore examined the cell-type specificity and functional significance of tonic inhibition in layer 4 of the mouse somatosensory barrel cortex. In situ hybridization and immunocytochemistry showed moderate delta-subunit expression across the barrel structures. Whole cell patch-clamp recordings additionally indicated that significant levels of tonic inhibition can be found across cell types, with differences in the magnitude of inhibition between cell types. To activate tonic currents, we used 4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridin-3-ol ( THIP, a superagonist at delta-subunit-containing GABA(A) receptors) at a concentration that did not affect synaptic decay kinetics. THIP produced greater shifts in baseline holding current in inhibitory cells ( low-threshold spiking [LTS], 109 +/- 17 pA; fast spiking [FS], 111 +/- 15 pA) than in excitatory cells (39 +/- 10 pA; P < 0.001). In addition to these differences across cell types, there was also variability within inhibitory cells. FS cells with faster action potentials had larger baseline shifts. Because FS cells are known mediators of feedforward inhibition, we tested whether THIP-induced tonic conductance selectively controls feedforward circuits. THIP application resulted in the abolishment of the inhibitory postsynaptic potential in thalamic-evoked disynaptic responses in a subset of excitatory neurons. These data suggest multiple feedforward circuits can be differentiated by the inhibitory control of the presynaptic inhibitory neuron.