Differentially Organized Top-Down Modulation of Prepulse Inhibition of Startle
Differentially Organized Top-Down Modulation of Prepulse Inhibition of Startle
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惊吓前脉冲抑制的差异组织自上而下调节
DOI：
10.1523/jneurosci.1292-11.2011
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发表时间：
2011-09-21
影响因子：
5.3
通讯作者：
Li, Liang
中科院分区：
文献类型：
--
作者：
Du, Yi;Wu, Xihong;Li, Liang
惊吓前脉冲抑制（PPI）是当一个较弱的感觉刺激（前脉冲）出现在惊吓刺激之前时对惊吓反射的抑制。PPI可以在人类和实验室动物中引起注意力增强。本研究探讨是否以下三个前脑结构，这是关键的初始皮层处理的听觉信号，听觉恐惧条件/记忆，空间注意，分别在自上而下的调制PPI在大鼠中发挥作用：初级听觉皮层（A1），杏仁核（LA）的外侧核，和后顶叶皮层（PPC）。结果表明，在噪声掩蔽条件下，前脉冲的恐惧条件化以前脉冲特异性方式增强PPI，条件化前脉冲与噪声掩蔽物之间的知觉分离进一步增强条件化引起的PPI增强。可逆地阻断谷氨酸受体在A1与2 mM犬尿烯酸消除条件诱导和知觉分离诱导的PPI增强。阻断左心房可以消除条件反射引起的PPI增强，但不能消除知觉分离引起的PPI增强，阻断PPC可以消除知觉分离引起的PPI增强。这两种类型的PPI增强也消除了消光操纵。因此，PPI的自上而下的调制是不同的组织，并取决于各种前脑结构的操作。由于高阶认知过程的微调调制，PPI的功能可以更灵活地适应复杂的环境。PPI在大鼠中的自上而下的增强也可用于模拟一些精神障碍，如精神分裂症、注意缺陷/多动障碍和创伤后应激障碍。
Prepulse inhibition (PPI) of startle is the suppression of the startle reflex when a weaker sensory stimulus (the prepulse) shortly precedes the startling stimulus. PPI can be attentionally enhanced in both humans and laboratory animals. This study investigated whether the following three forebrain structures, which are critical for initial cortical processing of auditory signals, auditory fear conditioning/memories, and spatial attention, respectively, play a role in the top-down modulation of PPI in rats: the primary auditory cortex (A1), lateral nucleus of the amygdala (LA), and posterior parietal cortex (PPC). The results show that, under the noise-masking condition, PPI was enhanced by fear conditioning of the prepulse in a prepulse-specific manner, and the conditioning-induced PPI enhancement was further increased by perceptual separation between the conditioned prepulse and the noise masker. Reversibly blocking glutamate receptors in the A1 with 2mM kynurenic acid eliminated both the conditioning-induced and perceptual separation-induced PPI enhancements. Blocking the LA eliminated the conditioning-induced but not the perceptual separation-induced PPI enhancement, and blocking the PPC specifically eliminated the perceptual separation-induced PPI enhancement. The two types of PPI enhancements were also eliminated by the extinction manipulation. Thus, the top-down modulation of PPI is differentially organized and depends on operations of various forebrain structures. Due to the fine-tuned modulation by higher-order cognitive processes, functions of PPI can be more flexible to complex environments. The top-down enhancements of PPI in rats are also useful for modeling some mental disorders, such as schizophrenia, attention deficit/hyperactivity disorder, and posttraumatic stress disorder.