NORADRENERGIC MODULATION OF CHOLINERGIC NUCLEUS BASALIS NEURONS DEMONSTRATED BY IN-VITRO PHARMACOLOGICAL AND IMMUNOHISTOCHEMICAL EVIDENCE IN THE GUINEA-PIG BRAIN
NORADRENERGIC MODULATION OF CHOLINERGIC NUCLEUS BASALIS NEURONS DEMONSTRATED BY IN-VITRO PHARMACOLOGICAL AND IMMUNOHISTOCHEMICAL EVIDENCE IN THE GUINEA-PIG BRAIN
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DOI：
10.1111/j.1460-9568.1995.tb01145.x
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发表时间：
1995-07-01
影响因子：
3.4
通讯作者：
JONES, BE
中科院分区：
文献类型：
--
作者：
FORT, P;KHATEB, A;JONES, BE
本实验观察了去甲肾上腺素对豚鼠脑片胆碱能神经元电生理特性的影响。根据胆碱能细胞先前确定的固有膜特性，胆碱能细胞的区别在于存在低阈值的钙尖峰和瞬间的外向整流，这使它们除了具有紧张性放电外，还具有在低阈值爆发时放电的能力。电生理鉴定的对去甲肾上腺素有反应的胆碱能细胞的一个子集已经被填充了生物细胞素(或生物胺)，并在以前发表的报告中被记录为胆碱乙酰转移酶(ChAT)免疫反应。本研究对去甲肾上腺素反应、充满生物细胞素的/ChAT+细胞进行了定位，发现它们分布在无名质内的大量ChAT+细胞中。来自另一组去甲肾上腺素反应、电生理鉴定的胆碱能细胞的切片被多巴胺-β-羟基酶染色，以显示去甲肾上腺素能纤维对充满生物细胞素的神经元的神经支配。这些充满生物细胞素的神经元被中度静脉曲张的去甲肾上腺素能纤维丛包围，表面上与其胞体和树突毗邻的少量至中等数量的去甲肾上腺素能神经纤维相连。在浴中，去甲肾上腺素引起膜去极化和长时间的紧张性棘波放电。这种兴奋作用与膜输入电阻的增加有关，表明它是通过降低K+电导而发生的。当突触传递被消除(被河豚毒素或低钙/高镁离子)时，这些效应仍然存在，因此明显是突触后的。去甲肾上腺素的兴奋作用可被α(1)受体拮抗剂哌唑嗪阻断，但不能被α(2)受体拮抗剂育亨宾阻断；去甲肾上腺素的兴奋作用可被α(1)受体激动剂L苯肾上腺素所阻断，但不能被α(2)受体激动剂可乐定和UK14.304所阻断，表明其受α(1)肾上腺素能受体的介导。也有证据表明，β-肾上腺素能受体参与了这一作用，因为β-受体拮抗剂心得安部分减弱了去甲肾上腺素的作用，而β-受体激动剂异丙肾上腺素与去甲肾上腺素一样，单独或与α(1)-拮抗剂哌唑嗪一起应用时，膜去极化和张力性棘波放电增加。这些结果表明，去甲肾上腺素通过对α(1)-肾上腺素能受体的主要作用，但伴随着β-肾上腺素能受体的额外参与，使胆碱能神经元去极化和兴奋。这种作用倾向于驱动胆碱能细胞进入紧张性放电模式，并刺激或增加长时间重复发放尖峰的频率。因此，去甲肾上腺素能蓝斑神经元可以招募胆碱能基底神经元与它们一起活动，以促进觉醒时皮质的激活。
The effects of noradrenalin were tested upon electrophysiologically characterized cholinergic nucleus basalis neurons in guinea-pig brain slices. According to their previously established intrinsic membrane properties, the cholinergic cells were distinguished by the presence of low-threshold Ca2+ spikes and transient outward rectification that endowed them with the capacity to fire in low-threshold bursts in addition to a stow tonic discharge. A subset of the electrophysiologically identified cholinergic cells that responded to noradrenalin had been filled with biocytin (or biotinamide) and documented in previously published reports as choline acetyltransferase (ChAT)-immunoreactive. The noradrenalin-responsive, biocytin-filled/ChAT + cells were mapped in the present study and shown to be distributed within the substantia innominata amongst a large population of ChAT + cells. Slices from another subset of noradrenalin-responsive, electrophysiologically identified cholinergic cells were stained for dopamine-beta-hydroxylase to visualize the innervation of the biocytin-filled neurons by noradrenergic fibres. These biocytin-filled neurons were surrounded by a moderate plexus of varicose noradrenergic fibres and were ostensibly contacted by a small to moderate number of noradrenergic boutons abutting their soma and dendrites. Applied in the bath, noradrenalin produced membrane depolarization and a prolonged tonic spike discharge. This excitatory action was associated with an increase in membrane input resistance, suggesting that it occurred through reduction of a K+ conductance. These effects persisted when synaptic transmission was eliminated (by tetrodotoxin or low Ca2+/high Mg2+) and were therefore clearly postsynaptic. The excitatory effect of noradrenalin was blocked by the alpha(1)-adrenergic receptor antagonist prazosin and not by the alpha(2)-antagonist yohimbine, and it was mimicked by the alpha(1)-agonist L-phenylephrine but not by the alpha(2)-agonists clonidine and UK14.304, indicating mediation by an alpha(1)-adrenergic receptor. There was also evidence for a contribution by a beta-adrenergic receptor to the effect, since the beta-antagonist propranolol partially attenuated the effect of noradrenalin, and the beta-agonist isoproterenol produced, like noradrenalin, alone or when applied in the presence of the alpha(1)-antagonist prazosin, membrane depolarization and an increase in tonic spike discharge. These results indicate that through a predominant action upon alpha(1)-adrenergic receptors, but with the additional participation of beta-adrenergic receptors, noradrenalin depolarizes and excites cholinergic neurons. This action would tend to drive the cholinergic cells into a tonic mode of firing and to stimulate or increase the rate of repetitive spike discharge for prolonged periods. The noradrenergic locus coeruleus neurons could thereby recruit the cholinergic basalis neurons to act in tandem with them in facilitating cortical activation during wakefulness.