Masri Radi, Trageser Jason C, Bezdudnaya Tatiana, Li Ying, Keller Asaf
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 21201, USA.
J Neurophysiol. 2006 Nov;96(5):2265-73. doi: 10.1152/jn.00476.2006. Epub 2006 Jul 26.
We previously showed that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incertothalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that this pathway is modulated by the ascending brain stem cholinergic system, which regulates sleep-wake cycles and states of vigilance. We demonstrate that cholinergic inputs facilitate POm responses to vibrissae stimulation. Activation of the cholinergic system by stimulation of brain stem cholinergic nuclei (laterodorsal tegmental and the pedunculopontine tegmental) or by tail pinch significantly increased the magnitude of POm responses to vibrissae stimulation. Microiontophoresis of the muscarinic receptor agonist carbachol enhanced POm responses to vibrissae stimulation. Application of carbachol to an in vitro slice preparation reduced the frequency but not the amplitude of miniature inhibitory postsynaptic currents, indicating a presynaptic site of action for carbachol. We conclude that the cholinergic system facilitates POm responses by suppressing GABAergic inputs from ZI. We propose the state-dependent gating hypothesis, which asserts that differing behavioral states, regulated by the brain stem cholinergic system, modulate the flow of information through POm.
我们先前表明，γ-氨基丁酸能的未定带核（ZI）可抑制啮齿动物体感系统后内侧丘脑（POm）中触须诱发的反应。我们提出，这种抑制性的未定带-丘脑通路在不同行为状态下调节POm的反应。在此，我们检验了这样一种假说，即该通路受调节睡眠-觉醒周期和警觉状态的脑干胆碱能系统上行调节。我们证明，胆碱能输入促进POm对触须刺激的反应。通过刺激脑干胆碱能核团（外侧背盖和脚桥被盖）或夹尾激活胆碱能系统，可显著增加POm对触须刺激反应的幅度。毒蕈碱受体激动剂卡巴胆碱的微量离子透入增强了POm对触须刺激的反应。将卡巴胆碱应用于体外脑片标本，可降低微小抑制性突触后电流的频率，但不改变其幅度，表明卡巴胆碱作用于突触前位点。我们得出结论，胆碱能系统通过抑制来自ZI的γ-氨基丁酸能输入来促进POm反应。我们提出了状态依赖性门控假说，该假说认为，由脑干胆碱能系统调节的不同行为状态，可调节通过POm的信息流。
