Hirono Moritoshi, Nagao Soichi, Yanagawa Yuchio, Konishi Shiro
Organization for Research Initiatives and Development, Doshisha University, Kyoto 610-0394, Japan; Laboratory for Motor Learning Control, RIKEN BSI, Wako 351-0198, Japan.
Laboratory for Motor Learning Control, RIKEN BSI, Wako 351-0198, Japan.
Neuropharmacology. 2017 May 15;118:79-89. doi: 10.1016/j.neuropharm.2017.03.011. Epub 2017 Mar 11.
Cerebellar Purkinje cells (PCs) project their axon collaterals to underneath of the PC layer and make GABAergic synaptic contacts with globular cells, a subgroup of Lugaro cells. GABAergic transmission derived from the PC axon collaterals is so powerful that it could inhibit globular cells and regulate their firing patterns. However, the physiological properties and implications of the GABAergic synapses on globular cells remain unknown. Using whole-cell patch-clamp recordings from globular cells in the mouse cerebellum, we examined the monoaminergic modulation of GABAergic inputs to these cells. Application of either serotonin (5-HT) or noradrenaline (NA) excited globular cells, thereby leading to their firing. The 5-HT- and NA-induced firing was temporally confined and attenuated by GABAergic transmission, although 5-HT and NA exerted an inhibitory effect on the release of GABA from presynaptic terminals of PC axon collaterals. Agonists for 5-HT receptors and α-adrenoceptors mimicked the 5-HT- and NA-induced suppression of GABAergic activity. Through their differential modulatory actions on the cerebellar inhibitory neural circuits, 5-HT facilitated PC firing, whereas NA suppressed it. These results indicate that 5-HT and NA regulate the membrane excitability of globular cells and PCs through their differential modulation of not only the membrane potential but also GABAergic synaptic circuits. Monoaminergic modulation of the neural connections between globular cells and PCs could play a role in cerebellar motor coordination.
小脑浦肯野细胞（PCs）将其轴突侧支投射到PC层下方，并与球状细胞（Lugaro细胞的一个亚群）形成GABA能突触联系。源自PC轴突侧支的GABA能传递非常强大，足以抑制球状细胞并调节其放电模式。然而，球状细胞上GABA能突触的生理特性和意义仍不清楚。我们利用小鼠小脑球状细胞的全细胞膜片钳记录，研究了这些细胞GABA能输入的单胺能调制。应用5-羟色胺（5-HT）或去甲肾上腺素（NA）均可使球状细胞兴奋，从而导致其放电。尽管5-HT和NA对PC轴突侧支突触前终末释放GABA有抑制作用，但5-HT和NA诱导的放电在时间上受到限制，并被GABA能传递减弱。5-HT受体和α-肾上腺素能受体激动剂模拟了5-HT和NA诱导的GABA能活性抑制。通过对小脑抑制性神经回路的不同调节作用，5-HT促进PC放电，而NA抑制PC放电。这些结果表明，5-HT和NA不仅通过对膜电位的不同调节，而且通过对GABA能突触回路的不同调节，来调节球状细胞和PCs的膜兴奋性。球状细胞与PCs之间神经连接的单胺能调制可能在小脑运动协调中发挥作用。
