Than Marta, Szabo Bela
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albertstrasse 25, D-79104 Freiburg i. Br., Germany.
Eur J Neurosci. 2002 May;15(10):1575-84. doi: 10.1046/j.1460-9568.2002.01997.x.
Purkinje cells, the output neurons of the cerebellar cortex, receive inhibitory input from basket, stellate and neighbouring Purkinje cells. The aim of the present study was to clarify the role of GABAB receptors on neurons giving inhibitory input to Purkinje cells. In sagittal slices prepared from the cerebellar vermis of the rat, the GABAB receptor agonist baclofen lowered the frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs) recorded in Purkinje cells. These effects were prevented by the GABAB receptor antagonist CGP 55845. Two mechanisms were involved in the depression of the inhibitory input to Purkinje cells. The first mechanism was suppression of the firing of basket, stellate and Purkinje cells. The second mechanism was presynaptic inhibition of GABA release from terminals of the afferent axons. This was indicated by the finding that baclofen decreased the amplitude of IPSCs occurring in Purkinje cells synchronously with action potentials recorded in basket cells. A further support for the presynaptic inhibition is the observation that baclofen decreased the amplitude of autoreceptor currents which are due to activation of GABAA autoreceptors at axon terminals of basket cells by synaptically released GABA. The presynaptic inhibition was partly due to direct inhibition of the vesicular release mechanism, because baclofen lowered the frequency of miniature IPSCs recorded in Purkinje cells in the presence of cadmium and in the presence of tetrodotoxin plus ionomycin. The results show that activation of GABAB receptors decreased GABAA receptor-mediated synaptic input to cerebellar Purkinje cells both by lowering the firing rate of the inhibitory input neurons and by inhibiting GABA release from their axon terminals with a presynaptic mechanism.
浦肯野细胞是小脑皮质的输出神经元，接受来自篮状细胞、星状细胞及相邻浦肯野细胞的抑制性输入。本研究的目的是阐明GABAB受体在向浦肯野细胞提供抑制性输入的神经元上的作用。在从大鼠小脑蚓部制备的矢状切片中，GABAB受体激动剂巴氯芬降低了浦肯野细胞中记录到的自发性抑制性突触后电流（IPSCs）的频率和幅度。这些效应被GABAB受体拮抗剂CGP 55845阻断。对浦肯野细胞抑制性输入的抑制涉及两种机制。第一种机制是抑制篮状细胞、星状细胞和浦肯野细胞的放电。第二种机制是对传入轴突终末GABA释放的突触前抑制。这一结论是通过以下发现得出的：巴氯芬降低了与篮状细胞中记录到的动作电位同步出现的浦肯野细胞中IPSCs的幅度。对突触前抑制的进一步支持是观察到巴氯芬降低了自身受体电流的幅度，该电流是由于突触释放的GABA激活篮状细胞轴突终末的GABAA自身受体所致。突触前抑制部分是由于对囊泡释放机制的直接抑制，因为在镉存在以及河豚毒素加离子霉素存在的情况下，巴氯芬降低了浦肯野细胞中记录到的微小IPSCs的频率。结果表明，GABAB受体的激活通过降低抑制性输入神经元的放电频率以及通过突触前机制抑制其轴突终末的GABA释放，减少了GABAA受体介导的对小脑浦肯野细胞的突触输入。
