Impact of Basal Forebrain Cholinergic Inputs on Basolateral Amygdala Neurons
Impact of Basal Forebrain Cholinergic Inputs on Basolateral Amygdala Neurons
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DOI：
10.1523/jneurosci.2706-14.2015
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发表时间：
2015-01-14
影响因子：
5.3
通讯作者：
Zaborszky, Laszlo
中科院分区：
文献类型：
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作者：
Unal, Cagri T.;Pare, Denis;Zaborszky, Laszlo
除了支配大脑皮层外，基底前脑胆碱能（BFc）神经元还向杏仁核基底外侧核（BLA）发送密集的投射。在这项研究中，我们利用光遗传学工具和体外膜片钳记录研究了近生理性乙酰胆碱释放对BLA神经元的影响。利用在胆碱乙酰转移酶启动子下表达re-重组酶的成年转基因小鼠，通过注射腺相关病毒选择性地用通道视紫红质-2和一个报告基因转导BFc神经元。光刺激BFc轴突对BLA细胞类型的影响不同。在晚放电的中间神经元中，BFc输入引发了快速的尼古丁epsp。相比之下，在快速尖峰的中间神经元中没有检测到反应。在主要的BLA神经元中，根据它们的活动水平，引发了两种不同的效应。当主要的BLA神经元处于静止状态或通过去极化电流注入以低速率放电时，BF轴突的光诱导激活会引发毒蕈碱ipsp。相比之下，在更强的去极化电流下，引发类似6-8Hz以上的放电，这些毒蕈碱ipsp失去了功效，因为BFc输入的刺激延长了电流引起的后去极化。在主神经元中观察到的所有作用都依赖于毒蕈碱受体1型，以状态依赖的方式参与不同的细胞内机制。总的来说，我们的研究结果表明，乙酰胆碱提高了主要BLA神经元的信噪比。此外，后去极化的胆碱能参与可能有助于恐惧条件反射任务中刺激关联的形成，其中条件和非条件刺激的时间不是诱导突触可塑性的最佳时机。
In addition to innervating the cerebral cortex, basal forebrain cholinergic (BFc) neurons send a dense projection to the basolateral nucleus of the amygdala (BLA). In this study, we investigated the effect of near physiological acetylcholine release on BLA neurons using optogenetic tools and in vitro patch-clamp recordings. Adult transgenic mice expressing cre-recombinase under the choline acetyltransferase promoter were used to selectively transduce BFc neurons with channelrhodopsin-2 and a reporter through the injection of an adeno-associated virus. Light-induced stimulation of BFc axons produced different effects depending on the BLA cell type. In late-firing interneurons, BFc inputs elicited fast nicotinic EPSPs. In contrast, no response could be detected in fast-spiking interneurons. In principal BLA neurons, two different effects were elicited depending on their activity level. When principal BLA neurons were quiescent or made to fire at low rates by depolarizing current injection, light-induced activation of BF caxons elicited muscarinic IPSPs. In contrast, with stronger depolarizing currents, eliciting firing above similar to 6-8Hz, these muscarinic IPSPs lost their efficacy because stimulation of BFc inputs prolonged current-evoked afterdepolarizations. All the effects observed in principal neurons were dependent on muscarinic receptors type 1, engaging different intracellular mechanisms in a state-dependent manner. Overall, our results suggest that acetylcholine enhances the signal-to-noise ratio in principal BLA neurons. Moreover, the cholinergic engagement of afterdepolarizations may contribute to the formation of stimulus associations during fear-conditioning tasks where the timing of conditioned and unconditioned stimuli is not optimal for the induction of synaptic plasticity.