Wu Shu Hui, Ma Chun Lei, Kelly Jack B
Institute of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
J Neurosci. 2004 May 12;24(19):4625-34. doi: 10.1523/JNEUROSCI.0318-04.2004.
The central nucleus of the inferior colliculus (ICC) is a major site of synaptic interaction in the central auditory system. To understand how ICC neurons integrate excitatory and inhibitory inputs for processing temporal information, we examined postsynaptic responses of ICC neurons to repetitive stimulation of the lateral lemniscus at 10-100 Hz in rat brain slices. The excitatory synaptic currents mediated by AMPA and NMDA receptors and the inhibitory current mediated by GABA(A) receptors were pharmacologically isolated and recorded by whole-cell patch-clamp techniques. The response kinetics of AMPA receptor-mediated EPSCs and GABA(A) receptor-mediated IPSCs were similar and much faster than those of NMDA receptor-mediated EPSCs. AMPA EPSCs could follow each pulse of stimulation at a rate of 10-100 Hz but showed response depression during the course of repetitive stimulation. GABA(A) IPSCs could also follow stimulus pulses over this frequency range but showed depression at low rates and facilitation at higher rates. NMDA EPSCs showed facilitation and temporal summation in response to repetitive stimulation, which was most pronounced at higher rates of stimulation. GABA(A) inhibition suppressed activation of NMDA receptors and reduced both the degree of AMPA EPSC depression and the extent of temporal summation of NMDA EPSCs. The results indicate that GABA(A) receptor-mediated inhibition plays a crucial role in maintaining the balance of excitation and inhibition and in allowing ICC neurons to process temporal information more precisely.
下丘中央核(ICC)是中枢听觉系统中突触相互作用的主要部位。为了解ICC神经元如何整合兴奋性和抑制性输入以处理时间信息,我们在大鼠脑片中,以10 - 100Hz的频率重复刺激外侧丘系,检测了ICC神经元的突触后反应。通过全细胞膜片钳技术,药理学分离并记录了由AMPA和NMDA受体介导的兴奋性突触电流以及由GABA(A)受体介导的抑制性电流。AMPA受体介导的兴奋性突触后电流(EPSCs)和GABA(A)受体介导的抑制性突触后电流(IPSCs)的反应动力学相似,且比NMDA受体介导的EPSCs快得多。AMPA EPSCs能够以10 - 100Hz的频率跟随每个刺激脉冲,但在重复刺激过程中表现出反应抑制。GABA(A) IPSCs也能够在这个频率范围内跟随刺激脉冲,但在低频率时表现出抑制,在高频率时表现出易化。NMDA EPSCs在重复刺激时表现出易化和时间总和,在较高刺激频率时最为明显。GABA(A)抑制作用抑制了NMDA受体的激活,并减少了AMPA EPSC抑制的程度以及NMDA EPSCs的时间总和程度。结果表明,GABA(A)受体介导的抑制在维持兴奋和抑制的平衡以及使ICC神经元更精确地处理时间信息方面起着关键作用。