Involvement of Nicotinic and Muscarinic Receptors in the Endogenous Cholinergic Modulation of the Balance between Excitation and Inhibition in the Young Rat Visual Cortex
Involvement of Nicotinic and Muscarinic Receptors in the Endogenous Cholinergic Modulation of the Balance between Excitation and Inhibition in the Young Rat Visual Cortex
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DOI：
10.1093/cercor/bhn258
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发表时间：
2009-10-01
期刊：
影响因子：
3.7
通讯作者：
Fossier, Philippe
中科院分区：
文献类型：
--
作者：
Lucas-Meunier, Estelle;Monier, Cyril;Fossier, Philippe
本研究旨在阐明内源性皮质乙酰胆碱（ACh）的释放如何调节视皮层兴奋与抑制之间的平衡。我们发现，在第1层的电刺激产生了显着的释放ACh测定内皮层化学发光和诱发复合突触反应记录在细胞内的第5层锥体神经元的大鼠视皮层。乙酰胆碱神经调节的药理学特异性从连续的全细胞电压钳测量胆碱能激动剂和拮抗剂的应用过程中的输入电导的刺激锁定的变化来确定。阻断乙酰胆碱能和γ-氨基丁酸（GABA能）受体抑制了诱发反应，表明刺激诱导的ACh释放不会直接激活记录神经元中的胆碱能突触电导。野靛碱和美加明对烟碱受体作用的比较表明，兴奋是通过突触前激活α（*）β 4受体而增强的。选择性α 4 β 2烟碱受体拮抗剂DH β E可诱导抑制性降低。内源性ACh也可通过直接作用于记录细胞突触前的GABA能中间神经元而增强抑制。我们的结论是，内源性释放ACh放大了抑制驱动的优势，从而降低了第5层锥体神经元的兴奋性和感觉反应性。
This study aims to clarify how endogenous release of cortical acetylcholine (ACh) modulates the balance between excitation and inhibition evoked in visual cortex. We show that electrical stimulation in layer 1 produced a significant release of ACh measured intracortically by chemoluminescence and evoked a composite synaptic response recorded intracellularly in layer 5 pyramidal neurons of rat visual cortex. The pharmacological specificity of the ACh neuromodulation was determined from the continuous whole-cell voltage clamp measurement of stimulation-locked changes of the input conductance during the application of cholinergic agonists and antagonists. Blockade of glutamatergic and gamma-aminobutyric acid (GABAergic) receptors suppressed the evoked response, indicating that stimulation-induced release of ACh does not directly activate a cholinergic synaptic conductance in recorded neurons. Comparison of cytisine and mecamylamine effects on nicotinic receptors showed that excitation is enhanced by endogenous evoked release of ACh through the presynaptic activation of alpha(*)beta 4 receptors located on glutamatergic fibers. DH beta E, the selective alpha 4 beta 2 nicotinic receptor antagonist, induced a depression of inhibition. Endogenous ACh could also enhance inhibition by acting directly on GABAergic interneurons, presynaptic to the recorded cell. We conclude that endogenous-released ACh amplifies the dominance of the inhibitory drive and thus decreases the excitability and sensory responsiveness of layer 5 pyramidal neurons.