Rohleder Cathrin, Jung Fabienne, Mertgens Hanna, Wiedermann Dirk, Sué Michael, Neumaier Bernd, Graf Rudolf, Leweke F Markus, Endepols Heike
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University Mannheim, Germany ; Multimodal Imaging, Max Planck Institute for Neurological Research Cologne, Germany.
Multimodal Imaging, Max Planck Institute for Neurological Research Cologne, Germany.
Front Behav Neurosci. 2014 May 22;8:178. doi: 10.3389/fnbeh.2014.00178. eCollection 2014.
Impaired sensorimotor gating occurs in neuropsychiatric disorders such as schizophrenia and can be measured using the prepulse inhibition (PPI) paradigm of the acoustic startle response. This assay is frequently used to validate animal models of neuropsychiatric disorders and to explore the therapeutic potential of new drugs. The underlying neural network of PPI has been extensively studied with invasive methods and genetic modifications. However, its relevance for healthy untreated animals and the functional interplay between startle- and PPI-related areas during a PPI session is so far unknown. Therefore, we studied awake rats in a PPI paradigm, startle control and background noise control, combined with behavioral [(18)F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET). Subtractive analyses between conditions were used to identify brain regions involved in startle and PPI processing in well-hearing Black hooded rats. For correlative analysis with regard to the amount of PPI we also included hearing-impaired Lister hooded rats that startled more often, because their hearing threshold was just below the lowest prepulses. Metabolic imaging showed that the brain areas proposed for startle and PPI mediation are active during PPI paradigms in healthy untreated rats. More importantly, we show for the first time that the whole PPI modulation network is active during "passive" PPI sessions, where no selective attention to prepulse or startle stimulus is required. We conclude that this reflects ongoing monitoring of stimulus significance and constant adjustment of sensorimotor gating.
感觉运动门控受损发生在精神分裂症等神经精神疾病中，可使用听觉惊吓反应的预脉冲抑制（PPI）范式进行测量。该检测方法常用于验证神经精神疾病的动物模型，并探索新药的治疗潜力。PPI的潜在神经网络已通过侵入性方法和基因修饰进行了广泛研究。然而，其与未经治疗的健康动物的相关性以及在PPI实验过程中惊吓相关区域和PPI相关区域之间的功能相互作用至今尚不清楚。因此，我们在PPI范式、惊吓控制和背景噪声控制中研究清醒大鼠，并结合行为学[（18）F]氟-2-脱氧葡萄糖正电子发射断层扫描（FDG-PET）。通过条件之间的减法分析来确定听力良好的黑帽大鼠中参与惊吓和PPI处理的脑区。为了对PPI量进行相关分析，我们还纳入了听力受损的利斯特帽大鼠，它们更容易受到惊吓，因为它们的听力阈值刚好低于最低预脉冲。代谢成像显示，在健康未治疗大鼠的PPI范式中，用于惊吓和PPI调节的脑区是活跃的。更重要的是，我们首次表明，在“被动”PPI实验过程中，整个PPI调节网络是活跃的，在该过程中不需要对预脉冲或惊吓刺激进行选择性注意。我们得出结论，这反映了对刺激重要性的持续监测和感觉运动门控的不断调整。
