Bell L Andrew, Bell Karen A, McQuiston A Rory
Department of Anatomy and Neurobiology, Virginia Commonwealth University Richmond, VA, USA.
Front Cell Neurosci. 2015 Apr 13;9:115. doi: 10.3389/fncel.2015.00115. eCollection 2015.
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 α4 and β2 subunits (α4β2*). ACh release onto VIP/IS was presynaptically inhibited by M2 muscarinic autoreceptors. ACh release produced spontaneous inhibitory postsynaptic current (sIPSC) barrages blocked by dihydro-β-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 α4β2* 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 α4β2* nicotinic receptors on interneuron-selective interneurons whereas interneurons that innervate pyramidal neurons are less affected by nicotinic receptor activation.
乙酰胆碱（ACh）释放到烟碱型受体上可直接激活海马CA1区的抑制性中间神经元亚群。然而，被激活的具体中间神经元及其对海马网络的影响尚未完全明确。因此，我们研究了海马CA1区中间神经元亚群，这些亚群通过烟碱型受体的激活对ACh释放产生反应，以及这可能对海马CA1区网络功能产生的潜在下游效应。通过使用依赖于Cre重组酶的腺相关病毒介导的转染，在小鼠海马切片的内侧隔区/布罗卡斜角带胆碱能神经元中表达兴奋性光遗传学蛋白oChIEF-tdTomato，从而光遗传学释放ACh。通过全细胞膜片钳方法评估光遗传学释放的ACh对锥体神经元和不同中间神经元亚型的作用。表达血管活性肠肽（VIP）的中间神经元选择性地支配其他中间神经元（VIP/IS），ACh通过激活含有α4和β2亚基的烟碱型受体（α4β2*）使其兴奋。ACh释放到VIP/IS上会被M2毒蕈碱自身受体突触前抑制。ACh释放产生的自发性抑制性突触后电流（sIPSC）阵发放可被二氢-β-刺桐啶在中间神经元中阻断，但在锥体神经元中则不然。对VIP中间神经元的光遗传学抑制并未抑制这些sIPSC阵发放，这表明其他中间神经元选择性中间神经元也被α4β2烟碱型受体激活所兴奋。相比之下，支配锥体神经元胞体周围区域的中间神经元不会因ACh释放到烟碱型受体上而被激活。因此，我们提出CA1区的ACh释放通过激活中间神经元选择性中间神经元上的α4β2烟碱型受体促进去抑制作用，而支配锥体神经元的中间神经元受烟碱型受体激活的影响较小。
