Collin Thibault, Franconville Romain, Ehrlich Barbara E, Llano Isabel
Centre National de la Recherche Scientifique, Laboratoire de Physiologie Cérébrale, Université Paris Descartes, Paris 75006, France.
J Neurosci. 2009 Jul 22;29(29):9281-91. doi: 10.1523/JNEUROSCI.1865-09.2009.
Little is known about the generation of slow rhythms in brain neuronal circuits. Nevertheless, a few studies, both from reconstituted systems and from hippocampal slices, indicate that activation of metabotropic glutamate receptors (mGluRs) could generate such rhythms. Here we show in rat cerebellar slices that after either release of glutamate by repetitive stimulation, or direct stimulation of type 1 mGluRs, molecular layer interneurons exhibit repetitive slow Ca(2+) transients. By combining cell-attached patch-clamp recording with Ca(2+) imaging, we show that the regular Ca(2+) transients (mean frequency, 35 mHz induced by 2 microm quisqualate in the presence of ionotropic glutamate receptor blockers) are locked with bursts of action potentials. Nevertheless, the Ca(2+) transients are not blocked by tetrodotoxin, indicating that firing is not necessary to entrain oscillations. The first Ca(2+) transient within a train is different in several ways from subsequent transients. It is broader than the subsequent transients, displays a different phase relationship to associated spike bursts, and exhibits a distinct sensitivity to ionic and pharmacological manipulations. Whereas the first transient appears to involve entry of Ca(2+) ions through transient receptor potential channel-like channels and secondarily activated L-type Ca(2+) channels, subsequent transients rely mostly on an exchange of Ca(2+) ions between the cytosol and D-myo-inositol-1,4,5-triphosphate-sensitive intracellular Ca(2+) stores. The slow, highly regular oscillations observed in the present work are likely to drive pauses in postsynaptic Purkinje cells, and could play a role in coordinating slow oscillations involving the cerebello-olivar circuit loop.
关于大脑神经元回路中慢节律的产生，目前所知甚少。然而，一些来自重组系统和海马切片的研究表明，代谢型谷氨酸受体（mGluRs）的激活可能会产生这种节律。在此，我们在大鼠小脑切片中发现，无论是通过重复刺激释放谷氨酸，还是直接刺激1型mGluRs，分子层中间神经元都会出现重复性的缓慢Ca(2+)瞬变。通过将细胞贴附式膜片钳记录与Ca(2+)成像相结合，我们发现，在离子型谷氨酸受体阻滞剂存在的情况下，由2微摩尔喹啉酸诱导的规则Ca(2+)瞬变（平均频率为35毫赫兹）与动作电位爆发同步。然而，Ca(2+)瞬变不受河豚毒素的阻断，这表明放电对于引发振荡并非必要条件。一串Ca(2+)瞬变中的第一个瞬变在几个方面与后续瞬变不同。它比后续瞬变更宽，与相关的尖峰爆发呈现不同的相位关系，并且对离子和药理学操作表现出独特的敏感性。第一个瞬变似乎涉及Ca(2+)离子通过类瞬时受体电位通道样通道进入，随后激活L型Ca(2+)通道，而后续瞬变主要依赖于Ca(2+)离子在细胞质和D-肌醇-1,4,5-三磷酸敏感的细胞内Ca(2+)储存库之间的交换。在本研究中观察到的缓慢、高度规则的振荡可能会驱动突触后浦肯野细胞的暂停，并可能在协调涉及小脑-橄榄回路环的慢振荡中发挥作用。
