Distinct roles of GABAB1a- and GABAB1b-containing GABAB receptors in spontaneous and evoked termination of persistent cortical activity
Distinct roles of GABAB1a- and GABAB1b-containing GABAB receptors in spontaneous and evoked termination of persistent cortical activity
复制标题
DOI：
10.1113/jphysiol.2012.248088
复制
发表时间：
2013-02-01
影响因子：
5.5
通讯作者：
McBain, Chris J.
中科院分区：
文献类型：
--
作者：
Craig, Michael T.;Mayne, Elizabeth W.;McBain, Chris J.
在慢波睡眠期间，皮质神经元在持续活动期（UP状态）和相对静止期（Down状态）之间表现出同步波动。这种UP和DOWN状态也见于孤立的皮质切片。最近，我们报道了自发和诱发终止UP状态的切片从大鼠内侧内嗅皮层（mEC）涉及GABAB受体。在这里，为了分离GABAB1a和GABAB1b受体在终止UP状态中的作用，我们使用了来自小鼠的mEC切片，其中GABAB1a或GABAB1b亚基已被遗传消融。使用拮抗剂CGP 55845对GABAB受体进行药理学阻断，延长了野生型小鼠和缺乏GABAB 1b亚基的小鼠的UP状态持续时间，但在缺乏GABAB 1a亚基的小鼠中则没有。相反，对第1层的电刺激可以终止野生型小鼠和缺乏GABAB 1a亚基的小鼠中正在进行的UP状态，但不能终止缺乏GABAB 1b亚基的小鼠中的UP状态。与以前的报告，表明一个优先的突触前位置的GABAB1a和突触后位置的GABAB1b的受体，这些结果表明，突触前GABAB受体有助于自发向下状态转换，而突触后GABAB受体是必不可少的传入终止的UP状态。因此，来自其他脑区的层1的输入可以提供一种强大的机制，用于通过激活靶向突触后GABAB受体的GABA能中间神经元来同步跨皮层区域的向下状态转换。
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.