Elghaba Rasha, Vautrelle Nicolas, Bracci Enrico
Department of Psychology, The University of Sheffield Sheffield, UK.
Front Cell Neurosci. 2016 Apr 29;10:111. doi: 10.3389/fncel.2016.00111. eCollection 2016.
The striatum is the largest nucleus of the basal ganglia and is crucially involved in action selection and reward processing. Cortical and thalamic inputs to the striatum are processed by local networks in which several classes of interneurons play an important, but still poorly understood role. Here we investigated the interactions between cholinergic and low-threshold spike (LTS) interneurons. LTS interneurons were hyperpolarized by co-application of muscarinic and nicotinic receptor antagonists (atropine and mecamylamine, respectively). Mecamylamine alone also caused hyperpolarizations, while atropine alone caused depolarizations and increased firing. LTS interneurons were also under control of tonic GABA, as application of the GABAA receptor antagonist picrotoxin caused depolarizations and increased firing. Frequency of spontaneous GABAergic events in LTS interneurons was increased by co-application of atropine and mecamylamine or by atropine alone, but reduced by mecamylamine alone. In the presence of picrotoxin and tetrodotoxin (TTX), atropine and mecamylamine depolarized the LTS interneurons. We concluded that part of the excitatory effects of tonic acetylcholine (ACh) on LTS interneurons were due to cholinergic modulation of tonic GABA. We then studied the influence of LTS interneurons on cholinergic interneurons. Application of antagonists of somatostatin or neuropeptide Y (NPY) receptors or of an inhibitor of nitric oxide synthase (L-NAME) did not cause detectable effects in cholinergic interneurons. However, prolonged synchronized depolarizations of LTS interneurons (elicited with optogenetics tools) caused slow-onset depolarizations in cholinergic interneurons, which were often accompanied by strong action potential firing and were fully abolished by L-NAME. Thus, a mutual excitatory influence exists between LTS and cholinergic interneurons in the striatum, providing an opportunity for sustained activation of the two cell types. This activation may endow the striatal microcircuits with the ability to enter a high ACh/high nitric oxide regime when adequately triggered by external excitatory stimuli to these interneurons.
纹状体是基底神经节中最大的核团，在动作选择和奖赏处理过程中起着至关重要的作用。皮质和丘脑向纹状体的输入由局部神经网络进行处理，在这些网络中，几类中间神经元发挥着重要但仍未被充分理解的作用。在这里，我们研究了胆碱能中间神经元和低阈值尖峰（LTS）中间神经元之间的相互作用。通过共同应用毒蕈碱和烟碱受体拮抗剂（分别为阿托品和美加明），LTS中间神经元发生超极化。单独使用美加明也会引起超极化，而单独使用阿托品则会引起去极化并增加放电频率。LTS中间神经元也受持续性GABA的控制，因为应用GABAA受体拮抗剂印防己毒素会引起去极化并增加放电频率。在LTS中间神经元中，共同应用阿托品和美加明或单独应用阿托品会增加自发性GABA能事件的频率，但单独使用美加明则会降低该频率。在存在印防己毒素和河豚毒素（TTX）的情况下，阿托品和美加明使LTS中间神经元去极化。我们得出结论，持续性乙酰胆碱（ACh）对LTS中间神经元的部分兴奋作用是由于胆碱能对持续性GABA的调制。然后，我们研究了LTS中间神经元对胆碱能中间神经元的影响。应用生长抑素或神经肽Y（NPY）受体拮抗剂或一氧化氮合酶抑制剂（L-NAME）在胆碱能中间神经元中未引起可检测到的效应。然而，LTS中间神经元的长时间同步去极化（用光遗传学工具诱发）会在胆碱能中间神经元中引起缓慢起始的去极化，这种去极化通常伴随着强烈的动作电位发放，并且被L-NAME完全消除。因此，纹状体中的LTS中间神经元和胆碱能中间神经元之间存在相互兴奋作用，为这两种细胞类型的持续激活提供了机会。当这些中间神经元受到外部兴奋性刺激充分触发时，这种激活可能赋予纹状体微回路进入高ACh/高一氧化氮状态的能力。
