PDF(Pubmed)
Abstract：
The hippocampus has been reported to be morphologically and neurochemically altered in schizophrenia (SZ). Hyperlocomotion is a characteristic SZ-associated behavioral phenotype, which is associated with dysregulated dopamine system function induced by hippocampal hyperactivity. However, the neural mechanism of hippocampus underlying hyperlocomotion remains largely unclear.
Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity.
We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment.
These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.
Mouse pups were injected with N-methyl-D-aspartate receptor antagonist (MK-801) or vehicle twice daily on postnatal days (PND) 7-11. In the adulthood phase, one cohort of mice underwent electrode implantation in field CA1 of the hippocampus for the recording local field potentials and spike activity. A separate cohort of mice underwent surgery to allow for calcium imaging of the hippocampus while monitoring the locomotion. Lastly, the effects of atypical antipsychotic (aripiprazole, ARI) were evaluated on hippocampal neural activity.
We found that the hippocampal theta oscillations were enhanced in MK-801-treated mice, but the correlation coefficient between the hippocampal spiking activity and theta oscillation was reduced. Consistently, although the rate and amplitude of calcium transients of hippocampal neurons were increased, their synchrony and correlation to locomotion speed were disrupted. ARI ameliorated perturbations produced by the postnatal MK-801 treatment.
These results suggest that the disruption of neural coordination may underly the neuropathological mechanism for hyperlocomotion of SZ.
摘要：
目的：据报道，精神分裂症（SZ）的海马在形态和神经化学上发生了改变。超运动是一种特征性的SZ相关行为表型，这与海马过度活动引起的多巴胺系统功能失调有关。然而,海马运动过度的神经机制尚不清楚。
方法:在出生后天数(PND)7-11每天两次给小鼠幼崽注射N-甲基-D-天冬氨酸受体拮抗剂(MK-801)或载体。在成年阶段，一组小鼠在海马CA1区进行电极植入,以记录局部场电位和尖峰活动.一组单独的小鼠接受了手术，以允许在监测运动的同时对海马进行钙成像。最后,非典型抗精神病药(阿立哌唑，ARI）对海马神经活动进行评估。
结果：我们发现MK-801处理的小鼠海马theta振荡增强，但海马尖峰活动与θ振荡的相关系数降低。始终如一，虽然海马神经元钙瞬变的速率和幅度增加，它们与运动速度的同步性和相关性被破坏。ARI改善了出生后MK-801治疗产生的扰动。
结论：这些结果表明，神经协调的破坏可能是SZ过度运动的神经病理机制。
方法:在出生后天数(PND)7-11每天两次给小鼠幼崽注射N-甲基-D-天冬氨酸受体拮抗剂(MK-801)或载体。在成年阶段，一组小鼠在海马CA1区进行电极植入,以记录局部场电位和尖峰活动.一组单独的小鼠接受了手术，以允许在监测运动的同时对海马进行钙成像。最后,非典型抗精神病药(阿立哌唑，ARI）对海马神经活动进行评估。
结果：我们发现MK-801处理的小鼠海马theta振荡增强，但海马尖峰活动与θ振荡的相关系数降低。始终如一，虽然海马神经元钙瞬变的速率和幅度增加，它们与运动速度的同步性和相关性被破坏。ARI改善了出生后MK-801治疗产生的扰动。
结论：这些结果表明，神经协调的破坏可能是SZ过度运动的神经病理机制。
