Department of Pharmacology, Southern Illinois University School of Medicine, 801 North Rutledge, Springfield, IL 62702, USA.
J Physiol. 2014 Feb 15;592(4):729-43. doi: 10.1113/jphysiol.2013.261941. Epub 2013 Oct 7.
Stimulus-specific adaptation (SSA), which describes adaptation to repeated sounds concurrent with the maintenance of responsiveness to uncommon ones, may be an important neuronal mechanism for the detection of and attendance to rare stimuli or for the detection of deviance. It is well known that GABAergic neurotransmission regulates several different response properties in central auditory system neurons and that GABA is the major inhibitory neurotransmitter acting in the medial geniculate body (MGB). The mechanisms underlying SSA are still poorly understood; therefore, the primary aim of the present study was to examine what role, if any, MGB GABAergic circuits play in the generation and/or modulation of SSA. Microiontophoretic activation of GABA(A) receptors (GABA(A)Rs) with GABA or with the selective GABA(A)R agonist gaboxadol significantly increased SSA (computed with the common SSA index, CSI) by decreasing responses to common stimuli while having a lesser effect on responses to novel stimuli. In contrast, GABA(A)R blockade using gabazine resulted in a significant decrease in SSA. In all cases, decreases in the CSI during gabazine application were accompanied by an increase in firing rate to the stimulus paradigm. The present findings, in conjunction with those of previous studies, suggest that GABA(A)-mediated inhibition does not generate the SSA response, but can regulate the level of SSA sensitivity in a gain control manner. The existence of successive hierarchical levels of processing through the auditory system suggests that the GABAergic circuits act to enhance mechanisms to reduce redundant information.
刺激特异性适应（SSA）描述了对重复声音的适应，同时保持对不常见声音的反应能力，这可能是检测和关注稀有刺激或检测偏差的重要神经元机制。众所周知，GABA 能神经传递调节中枢听觉系统神经元的几种不同反应特性，GABA 是作用于内侧膝状体（MGB）的主要抑制性神经递质。SSA 的机制仍知之甚少；因此，本研究的主要目的是研究 MGB GABA 能回路在 SSA 的产生和/或调节中起什么作用（如果有的话）。用 GABA 或选择性 GABAAR 激动剂 gaboxadol 微电泳激活 GABAAR（GABAARs）可显著增加 SSA（用常见 SSA 指数 CSI 计算），减少对常见刺激的反应，而对新刺激的反应影响较小。相比之下，GABAAR 阻断剂 gabazine 导致 SSA 显著下降。在所有情况下，gabazine 应用期间 CSI 的下降伴随着对刺激范式的放电率增加。本研究结果与以前的研究结果相结合，表明 GABA 能介导的抑制不会产生 SSA 反应，但可以以增益控制的方式调节 SSA 敏感性的水平。听觉系统中存在连续的分层处理水平表明 GABA 能回路的作用是增强减少冗余信息的机制。
