Compartmental distribution of GABAB receptor-mediated currents along the somatodendritic axis of hippocampal principal cells.
Compartmental distribution of GABAB receptor-mediated currents along the somatodendritic axis of hippocampal principal cells.
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DOI：
10.3389/fnsyn.2015.00006
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发表时间：
2015
影响因子：
3.7
通讯作者：
Vida I
中科院分区：
文献类型：
--
作者：
Degro CE;Kulik A;Booker SA;Vida I
皮层主细胞的活动由GABA能系统控制，GABA能系统以区室化的方式沿着其体树突轴提供抑制。虽然GABAAR介导的抑制性突触传递已被广泛表征在海马主细胞，很少有人知道的GABABR的突触后效应的分布。在本研究中，我们已经调查了功能定位的GABABR及其效应内向整流钾（Kir 3）通道相结合的电生理记录在急性大鼠海马脑片，高分辨率免疫电镜分析和单细胞模拟。药理学上孤立的慢抑制性突触后电流引起的三个主要的海马主要细胞类型的内源性GABA释放的电刺激，光解的笼状GABA，以及典型的激动剂巴氯芬，与观察到的最高幅度的CA 3。空间限制电流进行了评估沿着轴的主细胞释放GABA在不同的海马层。GABABR介导的电流存在沿着整个体树突轴的主细胞，但不均匀分布：最大的电流和最高的电导密度确定在模拟一致的远端顶端树突。最后，GABABR和Kir 3通道的免疫细胞化学定位显示，分布重叠，但它们的密度发散，特别是在锥体细胞的基底树突上。GABABRs电流幅度和电导密度与Kir 3密度相关性更好，表明效应通道定义了一种双重校验效应。这些数据表明GABABR-Kir 3信号级联的区室化分布，并表明在传入通路到海马主细胞的突触传递，树突整合和突触可塑性的差异控制。
Activity of cortical principal cells is controlled by the GABAergic system providing inhibition in a compartmentalized manner along their somatodendritic axis. While GABAAR-mediated inhibitory synaptic transmission has been extensively characterized in hippocampal principal cells, little is known about the distribution of postsynaptic effects of GABABRs. In the present study, we have investigated the functional localization of GABABRs and their effector inwardly rectifying potassium (Kir3) channels by combining electrophysiological recordings in acute rat hippocampal slices, high-resolution immunoelectron microscopic analysis and single cell simulations. Pharmacologically isolated slow inhibitory postsynaptic currents were elicited in the three major hippocampal principal cell types by endogenous GABA released by electrical stimulation, photolysis of caged-GABA, as well as the canonical agonist baclofen, with the highest amplitudes observed in the CA3. Spatially restricted currents were assessed along the axis of principal cells by uncaging GABA in the different hippocampal layers. GABABR-mediated currents were present along the entire somatodendritic axis of principal cells, but non-uniformly distributed: largest currents and the highest conductance densities determined in the simulations were consistently found on the distal apical dendrites. Finally, immunocytochemical localization of GABABRs and Kir3 channels showed that distributions overlap but their densities diverge, particularly on the basal dendrites of pyramidal cells. GABABRs current amplitudes and the conductance densities correlated better with Kir3 density, suggesting a bottlenecking effect defined by the effector channel. These data demonstrate a compartmentalized distribution of the GABABR-Kir3 signaling cascade and suggest differential control of synaptic transmission, dendritic integration and synaptic plasticity at afferent pathways onto hippocampal principal cells.