Bosch Daniel, Schmid Susanne
Tierphysiologie, Zoologisches Institut, Fakultät für Biologie, Universität Tübingen, Germany.
Eur J Neurosci. 2006 Oct;24(7):1967-75. doi: 10.1111/j.1460-9568.2006.05085.x. Epub 2006 Oct 16.
Giant neurones in the caudal pontine reticular nucleus (PnC) play a crucial role in mediating the mammalian startle response. They receive input from cochlear, trigeminal and vestibular nuclei and project directly to motoneurones. Furthermore, they integrate modulatory input from different brain regions either enhancing or inhibiting startle responses. One prominent startle modulation is prepulse inhibition where a non-startling stimulus presented prior to the startle stimulus inhibits a subsequent startle response. Several behavioural studies have indicated that this inhibition is mediated by muscarinic receptors at the level of the PnC. Here, we performed whole-cell patch-clamp recordings from PnC giant neurones in acute rat brain slices in order to examine muscarinic inhibition. We stimulated afferent trigeminal and auditory fibres and applied muscarinic agonists and antagonists in order to investigate their effect on excitatory postsynaptic current amplitudes, paired-pulse ratio and passive membrane properties of PnC giant neurones. The cholinergic agonist carbachol and the muscarinic agonist oxotremorine significantly reduced excitatory postsynaptic current amplitudes and increased the paired-pulse ratio. Carbachol additionally reduced the membrane resistance of postsynaptic PnC giant neurones. The subtype-specific antagonists AF-DX116 (M2 preferring) and tropicamide (M4 preferring) antagonized the oxotremorine effect indicating that M4 and possibly M2 receptor subtypes are involved in this inhibition. The G-protein-activated inward rectifying potassium channel blocker tertiapin-Q had no effect on oxotremorine-induced inhibition of giant neurones. Our results show a mainly presynaptically mediated strong inhibition of PnC giant neurones by activation of M4 and possibly M2 receptors that presumably contribute to prepulse inhibition.
脑桥尾侧网状核（PnC）中的巨大神经元在介导哺乳动物的惊吓反应中起着至关重要的作用。它们接收来自耳蜗核、三叉神经核和前庭核的输入，并直接投射到运动神经元。此外，它们整合来自不同脑区的调节性输入，增强或抑制惊吓反应。一种显著的惊吓调节是前脉冲抑制，即在惊吓刺激之前呈现的非惊吓刺激会抑制随后的惊吓反应。多项行为学研究表明，这种抑制是由PnC水平的毒蕈碱受体介导的。在此，我们在急性大鼠脑片上对PnC巨大神经元进行全细胞膜片钳记录，以研究毒蕈碱抑制作用。我们刺激传入的三叉神经和听觉纤维，并应用毒蕈碱激动剂和拮抗剂，以研究它们对PnC巨大神经元的兴奋性突触后电流幅度、配对脉冲比率和被动膜特性的影响。胆碱能激动剂卡巴胆碱和毒蕈碱激动剂氧化震颤素显著降低了兴奋性突触后电流幅度，并增加了配对脉冲比率。卡巴胆碱还降低了突触后PnC巨大神经元的膜电阻。亚型特异性拮抗剂AF-DX116（优先作用于M2）和托吡卡胺（优先作用于M4）拮抗了氧化震颤素的作用，表明M4以及可能的M2受体亚型参与了这种抑制作用。G蛋白激活的内向整流钾通道阻滞剂特律定-Q对氧化震颤素诱导的巨大神经元抑制作用没有影响。我们的结果表明，激活M4以及可能的M2受体主要在突触前介导对PnC巨大神经元的强烈抑制，这可能有助于前脉冲抑制。
