Neurophysiology Laboratory, Neuroscience Area, CIMA, Universidad de Navarra, Pamplona, Spain.
Neurophysiology Laboratory, Neuroscience Area, CIMA, Universidad de Navarra, Pamplona, Spain; Neurophysiology Service, Clínica Universidad de Navarra, Universidad de Navarra, Pamplona, Spain.
Eur Neuropsychopharmacol. 2015 Aug;25(8):1375-87. doi: 10.1016/j.euroneuro.2015.04.004. Epub 2015 Apr 14.
Recent studies have suggested the implication of the basal ganglia in the pathogenesis of schizophrenia. To investigate this hypothesis, here we have used the ketamine model of schizophrenia to determine the oscillatory abnormalities induced in the rat motor circuit of the basal ganglia. The activity of free moving rats was recorded in different structures of the cortico-basal ganglia circuit before and after an injection of a subanesthesic dose of ketamine (10mg/kg). Spectral estimates of the oscillatory activity, phase-amplitude cross-frequency coupling interactions (CFC) and imaginary event-related coherence together with animals׳ behavior were analyzed. Oscillatory patterns in the cortico-basal ganglia circuit were highly altered by the effect of ketamine. CFC between the phases of low-frequency activities (delta, 1-4; theta 4-8Hz) and the amplitude of high-gamma (80Hz) and high-frequency oscillations (HFO) (150Hz) increased dramatically and correlated with the movement increment shown by the animals. Between-structure analyses revealed that ketamine had also a massive effect in the low-frequency mediated synchronization of the HFO's across the whole circuit. Our findings suggest that ketamine administration results in an aberrant hypersynchronization of the whole cortico-basal circuit where the tandem theta/HFO seems to act as the main actor in the hyperlocomotion shown by the animals. Here we stress the importance of the basal ganglia circuitry in the ketamine model of schizophrenia and leave the door open to further investigations devoted to elucidate to what extent these abnormalities also reflect the prominent neurophysiological deficits observed in schizophrenic patients.
最近的研究表明基底神经节在精神分裂症的发病机制中起作用。为了验证这一假设，我们使用精神分裂症的氯胺酮模型来确定氯胺酮诱导的大鼠基底神经节运动回路的振荡异常。在给大鼠注射亚麻醉剂量的氯胺酮（10mg/kg）前后，记录自由活动大鼠不同结构的皮质基底神经节回路的活动。分析了振荡活动的频谱估计、相位-幅度交叉频率耦合相互作用（CFC）和虚拟事件相关相干性以及动物的行为。氯胺酮的作用极大地改变了皮质基底神经节回路中的振荡模式。低频活动（δ波，1-4Hz；θ波，4-8Hz）的相位与高频γ（80Hz）和高频振荡（HFO）（150Hz）的幅度之间的 CFC 显著增加，并与动物表现出的运动增量相关。结构间分析表明，氯胺酮对整个回路中 HFO 的低频介导同步化也有巨大影响。我们的发现表明，氯胺酮给药导致整个皮质基底回路的异常超同步化，串联的θ/HFO 似乎是动物表现出的过度运动的主要因素。在这里，我们强调了基底神经节回路在氯胺酮诱导的精神分裂症模型中的重要性，并为进一步的研究打开了大门，以阐明这些异常在多大程度上也反映了精神分裂症患者中观察到的突出的神经生理缺陷。
