Gauck Volker, Jaeger Dieter
Department of Cognitive Neurology, University of Tuebingen, 72076 Tuebingen, Germany.
J Neurosci. 2003 Sep 3;23(22):8109-18. doi: 10.1523/JNEUROSCI.23-22-08109.2003.
We performed whole-cell patch-clamp recordings in vitro to investigate the integration of excitatory and inhibitory inputs in neurons of the deep cerebellar nuclei (DCN) by applying synthetic synaptic input patterns with dynamic clamping. We explored an input regime in which excitation and inhibition had an ongoing baseline rate because both input pathways show ongoing activity in vivo. We found that spiking was time-locked to transients in the inputs, consisting of brief decreases in inhibitory or increases in excitatory conductance. Such input transients were caused by synchronization among multiple inputs. However, we found that temporal synchrony in the inhibitory input pathway had preferential access to the control of DCN spiking, because the large NMDA component of the excitatory inputs smoothed out temporal transients in this pathway. Thus, synaptic integration in the DCN appears to be tuned to allow the cerebellar cortical output from Purkinje cells preferential access to the control of DCN spiking. The effect of temporal modulations in the inhibition was further enhanced by the voltage dependence of the NMDA inputs. Thus, the presence of a baseline of mossy and climbing fiber inputs boosted depolarizing responses caused by reduced inhibition by the voltage-dependent increase in inward NMDA current. Overall, our results show that correlated activity or pauses in populations of Purkinje cells are well suited to the dynamic control of DCN spiking. In addition, strong transients in excitation can directly drive DCN responses that bypass cerebellar cortical processing.
我们在体外进行全细胞膜片钳记录，通过应用动态钳制的合成突触输入模式，研究小脑深部核团（DCN）神经元中兴奋性和抑制性输入的整合。我们探索了一种输入状态，即兴奋和抑制具有持续的基线速率，因为在体内这两种输入途径都显示出持续的活动。我们发现，动作电位发放与输入中的瞬变在时间上锁定，这些瞬变由抑制性电导的短暂降低或兴奋性电导的增加组成。这种输入瞬变是由多个输入之间的同步引起的。然而，我们发现抑制性输入途径中的时间同步对DCN动作电位发放的控制具有优先作用，因为兴奋性输入中的大NMDA成分使该途径中的时间瞬变变得平滑。因此，DCN中的突触整合似乎经过调整，以使浦肯野细胞的小脑皮质输出优先控制DCN动作电位发放。NMDA输入的电压依赖性进一步增强了抑制中时间调制的作用。因此，苔藓纤维和攀缘纤维输入基线的存在增强了由内向NMDA电流的电压依赖性增加导致的抑制减少所引起的去极化反应。总体而言，我们的结果表明，浦肯野细胞群体中的相关活动或暂停非常适合对DCN动作电位发放进行动态控制。此外，强烈的兴奋瞬变可以直接驱动绕过小脑皮质处理的DCN反应。
