Acetylcholine release in mouse hippocampal CA1 preferentially activates inhibitory-selective interneurons via α4β2*nicotinic receptor activation
Acetylcholine release in mouse hippocampal CA1 preferentially activates inhibitory-selective interneurons via α4β2*nicotinic receptor activation
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DOI：
10.3389/fncel.2015.00115
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发表时间：
2015-04-13
影响因子：
5.3
通讯作者：
McQuiston, A. Rory
中科院分区：
文献类型：
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作者：
Bell, L. Andrew;Bell, Karen A.;McQuiston, A. Rory
乙酰胆碱（ACh）释放到烟碱受体上直接激活海马CA1的抑制性中间神经元亚群。然而，被激活的特定中间神经元及其对海马体网络的影响尚不完全清楚。因此，我们研究了通过激活烟碱受体来响应ACh释放的海马CA1中间神经元亚群，以及这可能对海马CA1网络功能产生的潜在下游影响。通过Cre重组酶依赖的腺相关病毒介导转染，在Broca胆碱能神经元内侧隔/对角带表达兴奋性光遗传蛋白oChIEF-tdTomato，从而在小鼠海马切片中释放乙酰胆碱能。采用全细胞膜片钳法评价光敏释放乙酰胆碱对锥体神经元和不同中间神经元亚型的作用。乙酰胆碱通过激活含有α 4和β 2亚基的烟碱受体（α 4 β 2*），使表达血管活性肠肽（VIP）的中间神经元选择性支配其他中间神经元（VIP/IS）兴奋。M2毒蕈碱自受体突触前抑制乙酰胆碱释放到VIP/IS。乙酰胆碱释放在中间神经元中产生自发性抑制突触后电流（sIPSC），但在锥体神经元中没有。光遗传抑制VIP中间神经元并没有抑制sIPSC，这表明其他中间神经元选择性也被α 4 β 2*烟碱受体激活。相反，支配锥体神经元周围区域的中间神经元没有被释放到烟碱受体的乙酰胆碱激活。因此，我们提出CA1中的ACh释放通过激活神经元间选择性中间神经元上的α 4 β 2*烟碱受体促进去抑制，而支配锥体神经元的中间神经元受烟碱受体激活的影响较小。
Acetylcholine (ACh) release onto nicotinic receptors directly activates subsets of inhibitory interneurons in hippocampal CA1. However, the specific interneurons activated and their effect on the hippocampal network is not completely understood. Therefore, we investigated subsets of hippocampal CA1 interneurons that respond to ACh release through the activation of nicotinic receptors and the potential downstream effects this may have on hippocampal CA1 network function. ACh was optogenetically released in mouse hippocampal slices by expressing the excitatory optogenetic protein oChIEF-tdTomato in medial septum/diagonal band of Broca cholinergic neurons using Cre recombinase-dependent adeno-associated viral mediated transfection. The actions of optogenetically released ACh were assessed on both pyramidal neurons and different interneuron subtypes via whole cell patch clamp methods. Vasoactive intestinal peptide (VIP)-expressing interneurons that selectively innervate other interneurons (VIP/IS) were excited by ACh through the activation of nicotinic receptors containing alpha 4 and beta 2 subunits (alpha 4 beta 2*). ACh release onto VIP/IS was presynaptically inhibited by M2 muscarinic autoreceptors. ACh release produced spontaneous inhibitory postsynaptic current (sIPSC) barrages blocked by dihydro-beta-erythroidine in interneurons but not pyramidal neurons. Optogenetic suppression of VIP interneurons did not inhibit these sIPSC barrages suggesting other interneuron-selective interneurons were also excited by alpha 4 beta 2* nicotinic receptor activation. In contrast, interneurons that innervate pyramidal neuron perisomatic regions were not activated by ACh release onto nicotinic receptors. Therefore, we propose ACh release in CA1 facilitates disinhibition through activation of alpha 4 beta 2* nicotinic receptors on interneuron-selective interneurons whereas interneurons that innervate pyramidal neurons are less affected by nicotinic receptor activation.