Assessment of sensorimotor gating following selective lesions of cholinergic pedunculopontine neurons.
Assessment of sensorimotor gating following selective lesions of cholinergic pedunculopontine neurons.
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胆碱能脚桥神经元选择性损伤后感觉运动门控的评估。
DOI：
10.1111/ejn.12716
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Clark,StewartD
中科院分区：
文献类型：
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作者：
MacLaren,DuncanAA;Markovic,Tamara;Clark,StewartD
感觉运动门控是感觉信息进入运动系统的状态依赖的传输。当这发生在处理流的早期阶段时，它使刺激能够被过滤掉或部分被忽略，从而降低了对高级系统的要求。声惊厥反射(ASR)的预脉冲抑制(PPI)是感觉运动门控的标准测量。脑干-中脑回路被广泛认为是PPI和ASR的中介。在这个回路中，桥脑脚盖核(PPTg)整合了感觉输入和皮质-基底节输出，并通过推测的胆碱能信号，抑制网状结构内产生ASR的神经元。对PPTG内所有神经元类型的非选择性损伤可降低PPI。我们通过检测PPTg的非选择性(兴奋性毒性)或选择性胆碱能(DTX-UII)损害的大鼠的ASR和PPI来评估这种效应是否起源于胆碱能信号的丧失。刺激性损伤对ASR没有影响，但降低了所有脉冲前水平的PPI。相反，选择性去除胆碱能神经元可以降低ASR，以至于标准(S 10-20)试验间间隔无法测量PPI。随后的测试显示，当试验间间隔增加时，可以产生明显的ASR(S 180)。在此条件下，对PPI进行评估，发现胆碱能PPTg神经元损伤后没有发现任何缺陷。这些结果表明，PPTG的胆碱能输出是ASR快速再生所必需的，但对PPI没有影响。结果从感觉运动整合回路和精神障碍的角度进行了讨论，这些障碍的特点是ASR和PPI中断。
Sensorimotor gating is the state‐dependent transfer of sensory information into a motor system. When this occurs at an early stage of the processing stream it enables stimuli to be filtered out or partially ignored, thereby reducing the demands placed on advanced systems. Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) is the standard measure of sensorimotor gating. A brainstem–midbrain circuitry is widely viewed as mediating both PPI and ASR. In this circuitry, the pedunculopontine tegmental nucleus (PPTg) integrates sensory input and cortico‐basal ganglia output and, via presumed cholinergic signaling, inhibits ASR‐generating neurons within the reticular formation. Non‐selective damage to all neuronal types within PPTg reduces PPI. We assessed whether this effect originates in the loss of cholinergic signaling by examining ASR and PPI in rats bearing non‐selective (excitotoxic) or selective cholinergic (Dtx‐UII) lesions of PPTg. Excitotoxic lesions had no effect on ASR but reduced PPI at all prepulse levels tested. In contrast, selective depletion of cholinergic neurons reduced ASR to the extent that PPI was not measurable with standard (10–20 s) inter‐trial intervals. Subsequent testing revealed appreciable ASRs could be generated when the inter‐trial interval was increased (180 s). Under these conditions, PPI was assessed and no deficits were found after lesions of cholinergic PPTg neurons. These results show that cholinergic output from PPTg is essential for rapidly regenerating the ASR, but has no influence on PPI. Results are discussed in terms of sensorimotor integration circuitry and psychiatric disorders that feature disrupted ASR and PPI.