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首页> 外文期刊>The Journal of Physiology >Distinct roles of GABAB1a- and GABAB1b-containing GABAB receptors in spontaneous and evoked termination of persistent cortical activity
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Distinct roles of GABAB1a- and GABAB1b-containing GABAB receptors in spontaneous and evoked termination of persistent cortical activity

机译：含有GABAB1a和GABAB1b的GABAB受体在持续性皮层活动的自发和诱发终止中的不同作用

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During slow-wave sleep, cortical neurons display synchronous fluctuations between periods of persistent activity (UP states') and periods of relative quiescence (DOWN states'). Such UP and DOWN states are also seen in isolated cortical slices. Recently, we reported that both spontaneous and evoked termination of UP states in slices from the rat medial entorhinal cortex (mEC) involves GABAB receptors. Here, in order to dissociate the roles of GABAB1a- and GABAB1b-containing receptors in terminating UP states, we used mEC slices from mice in which either the GABAB1a or the GABAB1b subunit had been genetically ablated. Pharmacological blockade of GABAB receptors using the antagonist CGP55845 prolonged the UP state duration in both wild-type mice and those lacking the GABAB1b subunit, but not in those lacking the GABAB1a subunit. Conversely, electrical stimulation of layer 1 could terminate an ongoing UP state in both wild-type mice and those lacking the GABAB1a subunit, but not in those lacking the GABAB1b subunit. Together with previous reports, indicating a preferential presynaptic location of GABAB1a- and postsynaptic location of GABAB1b-containing receptors, these results suggest that presynaptic GABAB receptors contribute to spontaneous DOWN state transitions, whilst postsynaptic GABAB receptors are essential for the afferent termination of the UP state. Inputs to layer 1 from other brain regions could thus provide a powerful mechanism for synchronizing DOWN state transitions across cortical areas via activation of GABAergic interneurons targeting postsynaptic GABAB receptors.
机译：在慢波睡眠期间，皮质神经元在持续活动周期（“ UP状态”）和相对静止周期（“ DOWN状态”）之间显示同步波动。在孤立的皮质切片中也可以看到这种UP和DOWN状态。最近，我们报道了大鼠内侧内嗅皮层（mEC）的切片中UP状态的自发和诱发终止均涉及GABAB受体。在这里，为了解离在终止UP状态中含GABAB1a和GABAB1b的受体的作用，我们使用了来自小鼠的mEC切片，其中GABAB1a或GABAB1b亚基已被基因消融。在野生型小鼠和缺乏GABAB1b亚基的小鼠中，使用拮抗剂CGP55845药理阻断GABAB受体均可以延长UP状态持续时间，但在缺乏GABAB1a亚基的小鼠中则没有。相反，在野生型小鼠和缺乏GABAB1a亚基的小鼠中，第1层的电刺激可以终止正在进行的UP状态，而在缺乏GABAB1b亚基的小鼠中则不能。与以前的报道一起，表明优先的突触前GABAB1a-和含GABAB1b受体的突触位置，这些结果表明，突触前GABAB受体有助于自发的DOWN状态转变，而突触后GABAB受体对于UP状态的传入终止至关重要。因此，来自其他大脑区域的第1层输入可以通过激活针对突触后GABA B受体的GABA能中间神经元，提供跨皮层区域同步DOWN状态转变的强大机制。

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