Khateb A, Fort P, Pegna A, Jones B E, Mühlethaler M
Département de Physiologie, CMU, Genève, Switzerland.
Neuroscience. 1995 Nov;69(2):495-506. doi: 10.1016/0306-4522(95)00264-j.
Considerable evidence has shown that both cholinergic and histaminergic neurons in the brain may act to facilitate processes of cortical activation that occur during wakefulness. In the present study, the potential influence of histaminergic neurons upon cholinergic neurons of the basal forebrain was investigated in guinea-pig basal forebrain slices. We found that electrophysiologically identified and immunohistochemically verified cholinergic neurons of the nucleus basalis were depolarized and excited by histamine, as manifested by an increase in tonic firing. The depolarization was associated with an increase in membrane input resistance. The effect of histamine persisted in the presence of either tetrodotoxin or a high-magnesium/low-calcium solution, indicating that it is postsynaptic. By a process of elimination, the participation in this response of the three described histamine receptors was examined. Involvement of H3 receptors was excluded on the basis that the H3 agonist (R)-alpha-methyl-histamine had no direct effect, and the H3 antagonist, thioperamide, did not block the effect of histamine. In contrast, the presence of a small response to impromidine, a selective agonist of H2 receptors, and the partial block of the response to histamine by the H2 receptor antagonist, cimetidine, indicated the participation of H2 receptors. Finally, the complete elimination of histamine's effect occurred when low doses of the H1 antagonist, mepyramine, were added to the H2 antagonist, cimetidine, indicating the involvement and predominance of H1 receptors in the response. Our data thus suggest that histamine excites nucleus basalis cholinergic neurons by a concomitant activation of H1 and H2 receptors. Histaminergic tuberomammillary neurons may accordingly facilitate tonic firing of cholinergic neurons during wakefulness. Cholinergic basalis neurons could thus act in tandem with histaminergic neurons during periods of arousal to collectively promote widespread cortical activation.
大量证据表明，大脑中的胆碱能神经元和组胺能神经元均可促进清醒时发生的皮质激活过程。在本研究中，我们在豚鼠基底前脑切片中研究了组胺能神经元对基底前脑胆碱能神经元的潜在影响。我们发现，经电生理鉴定和免疫组化验证的基底核胆碱能神经元会因组胺而发生去极化并兴奋，表现为紧张性放电增加。去极化与膜输入电阻增加有关。组胺的作用在存在河豚毒素或高镁/低钙溶液的情况下仍然持续，这表明它是突触后作用。通过排除法，我们研究了三种所述组胺受体对该反应的参与情况。基于H3激动剂（R）-α-甲基组胺没有直接作用，且H3拮抗剂硫代哌啶不阻断组胺的作用，排除了H3受体的参与。相反，对H2受体选择性激动剂英普咪定有小反应，且H2受体拮抗剂西咪替丁对组胺反应有部分阻断作用，这表明H2受体参与其中。最后，当低剂量的H1拮抗剂美吡拉敏与H2拮抗剂西咪替丁一起添加时，组胺的作用完全消除，这表明H1受体在该反应中起作用且占主导地位。因此，我们的数据表明，组胺通过同时激活H1和H2受体来兴奋基底核胆碱能神经元。组胺能的结节乳头体神经元因此可能在清醒时促进胆碱能神经元的紧张性放电。胆碱能基底核神经元因此可以在觉醒期间与组胺能神经元协同作用，共同促进广泛的皮质激活。
