Kodsi M H, Swerdlow N R
Department of Neuroscience, UCSD School of Medicine, La Jolla 92093-0804.
Brain Res. 1994 Apr 18;643(1-2):59-65. doi: 10.1016/0006-8993(94)90008-6.
The startle reflex is inhibited when the startling stimulus is preceded 30-500 ms by a weak noise or 'prepulse'. While the primary startle circuit is organized at or below the pons, the amount of 'prepulse inhibition' (PPI) is modulated by forebrain activity and is reduced in certain neuropsychiatric disorders. The reduction of PPI in these disorders is thought to reflect disturbances in sensorimotor inhibition which underlie an inability to 'gate' irrelevant sensory, motor or cognitive information. PPI is altered by pharmacologic manipulations of the ventral striatum, which is thought to modulate PPI via sequential efferent projections through the ventral pallidum and pontine reticular formation. In the present study, we assessed the effects of cellular lesions of the ventral striatum (VS) on PPI. Quinolinic acid lesions of the VS significantly reduced PPI and increased startle amplitude; however, changes in PPI and startle amplitude were not significantly correlated within rats. Infusion of the GABA agonist muscimol into ventral striatal terminal fields in the ventral pallidum significantly restored PPI in VS-lesioned rats, but did not reverse lesion effects on startle amplitude. It was verified that muscimol infusions were made into an area which receives direct VS innervation, using ventral pallidal injections of the retrograde tracer Nuclear yellow in VS sham-lesioned rats. Cells in the ventral striatum appear to modulate sensorimotor gating of the startle reflex via a GABAergic innervation of the ventral pallidum.
当在惊吓刺激前30 - 500毫秒出现微弱噪声或“预脉冲”时，惊吓反射会受到抑制。虽然初级惊吓回路在脑桥或脑桥以下部位形成，但“预脉冲抑制”（PPI）的程度受前脑活动调节，并且在某些神经精神疾病中会降低。这些疾病中PPI的降低被认为反映了感觉运动抑制的紊乱，而感觉运动抑制是无法“筛选”无关的感觉、运动或认知信息的基础。通过对腹侧纹状体进行药理学操作可改变PPI，腹侧纹状体被认为是通过经腹侧苍白球和脑桥网状结构的顺序传出投射来调节PPI的。在本研究中，我们评估了腹侧纹状体（VS）细胞损伤对PPI的影响。VS的喹啉酸损伤显著降低了PPI并增加了惊吓幅度；然而，在大鼠中PPI和惊吓幅度的变化并无显著相关性。向腹侧苍白球的腹侧纹状体终末场注入GABA激动剂蝇蕈醇可显著恢复VS损伤大鼠的PPI，但并未逆转损伤对惊吓幅度的影响。在VS假损伤大鼠中，通过向腹侧苍白球注射逆行示踪剂核黄，证实蝇蕈醇注入的区域接受VS的直接神经支配。腹侧纹状体中的细胞似乎通过对腹侧苍白球的GABA能神经支配来调节惊吓反射的感觉运动门控。
