Self-tuning of inhibition by endocannabinoids shapes spike-time precision in CA1 pyramidal neurons

Self-tuning of inhibition by endocannabinoids shapes spike-time precision in CA1 pyramidal neurons
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DOI:
10.1152/jn.00099.2013
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发表时间:
2013-10-01
影响因子:
2.5
通讯作者:
Caillard, Olivier
Caillard, Olivier
中科院分区:
医学3区
文献类型:
--
作者:
Dubruc, Franck;Dupret, David;Caillard, Olivier

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在海马体中,突触传递和峰时协调的活动依赖的变化被认为是为记忆形成目的的信息处理的中介。在这里,我们研究了CA1海马区锥体细胞通过改变其GABA能抑制输入和内源性大麻素(ECB)信号对内在兴奋性和放电可靠性的自我调节。CA1Place细胞的放电模式在体外重放时,可诱导ECB依赖的自发性GABA能活动的一过性降低,具有去极化诱导的抑制抑制(DSI)的主要特征,并在连续的猝发放电中条件下尖峰时间精度的一过性提高。在评估DSI对兴奋性突触后电位(EPSP)-棘波耦合的影响时,我们发现,不相关(自发)或相关(前馈)抑制的瞬时降低提高了EPSP-棘波耦合的概率。然而,EPSP峰时可靠性与抑制之间的关系更为复杂:根据初始峰耦合概率,相关(前馈)抑制的瞬时降低扰乱或改善了峰时可靠性。因此,ECB介导的锥体细胞尖峰时间精确度的调节不仅受到全局抑制的初始水平的控制,还受到自发和前馈GABA能活动之间的比率的控制。这些结果表明,ECB介导的锥体细胞放电对棘波时序的自我调节可以对海马区的位置细胞组装和记忆形成做出重要贡献。
In the hippocampus, activity-dependent changes of synaptic transmission and spike-timing coordination are thought to mediate information processing for the purpose of memory formation. Here, we investigated the self-tuning of intrinsic excitability and spiking reliability by CA1 hippocampal pyramidal cells via changes of their GABAergic inhibitory inputs and endocannabinoid (eCB) signaling. Firing patterns of CA1 place cells, when replayed in vitro, induced an eCB-dependent transient reduction of spontaneous GABAergic activity, sharing the main features of depolarization-induced suppression of inhibition (DSI), and conditioned a transient improvement of spike-time precision during consecutive burst discharges. When evaluating the consequences of DSI on excitatory postsynaptic potential (EPSP)-spike coupling, we found that transient reductions of uncorrelated (spontaneous) or correlated (feedforward) inhibition improved EPSP-spike coupling probability. The relationship between EPSP-spike-timing reliability and inhibition was, however, more complex: transient reduction of correlated (feedforward) inhibition disrupted or improved spike-timing reliability according to the initial spike-coupling probability. Thus eCB-mediated tuning of pyramidal cell spike-time precision is governed not only by the initial level of global inhibition, but also by the ratio between spontaneous and feedforward GABAergic activities. These results reveal that eCB-mediated self-tuning of spike timing by the discharge of pyramidal cells can constitute an important contribution to place-cell assemblies and memory formation in the hippocampus.