Zhang J, Ma L, Li W, Yang P, Qin L
Department of Physiology, China Medical University, Shenyang 110001, People's Republic of China.
Department of Physiology, China Medical University, Shenyang 110001, People's Republic of China; Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001, People's Republic of China.
Neuroscience. 2016 Jun 2;324:29-39. doi: 10.1016/j.neuroscience.2016.03.006. Epub 2016 Mar 8.
As disturbance in auditory steady-state response (ASSR) has been consistently found in many neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia, there is considerable interest in the development of translational rat models to elucidate the underlying neural and neurochemical mechanisms involved in ASSR. This is the first study to investigate the effects of the non-selective muscarinic antagonist scopolamine and the cholinesterase inhibitor donepezil (also in combination with scopolamine) on ASSR. We recorded the local field potentials through the chronic microelectrodes implanted in the auditory cortex of freely moving rat. ASSRs were recorded in response to auditory stimuli delivered over a range of frequencies (10-80 Hz) and averaged over 60 trials. We found that a single dose of scopolamine produced a temporal attenuation in response to auditory stimuli; the most attenuation occurred at 40 Hz. Time-frequency analysis revealed deficits in both power and phase-locking to 40 Hz. Donepezil augmented 40-Hz steady-state power and phase-locking. Scopolamine combined with donepezil had an enhanced effect on the phase-locking, but not power of ASSR. These changes induced by cholinergic drugs suggest an involvement of muscarinic neurotransmission in auditory processing and provide a rodent model investigating the neurochemical mechanism of neurophysiological deficits seen in patients.
由于在许多神经精神疾病（如自闭症谱系障碍和精神分裂症）中一直发现听觉稳态反应（ASSR）存在紊乱，因此人们对开发转化大鼠模型以阐明ASSR潜在的神经和神经化学机制产生了浓厚兴趣。这是第一项研究非选择性毒蕈碱拮抗剂东莨菪碱和胆碱酯酶抑制剂多奈哌齐（也与东莨菪碱联合使用）对ASSR影响的研究。我们通过植入自由活动大鼠听觉皮层的慢性微电极记录局部场电位。记录ASSR对一系列频率（10 - 80Hz）的听觉刺激的反应，并在60次试验中进行平均。我们发现单剂量东莨菪碱会使对听觉刺激的反应出现时间衰减；最大衰减发生在40Hz。时频分析显示在功率和与40Hz的锁相方面均存在缺陷。多奈哌齐增强了40Hz的稳态功率和锁相。东莨菪碱与多奈哌齐联合使用对ASSR的锁相有增强作用，但对功率无增强作用。胆碱能药物引起的这些变化表明毒蕈碱神经传递参与了听觉处理，并提供了一个啮齿动物模型来研究患者中所见神经生理缺陷的神经化学机制。
