BACKGROUND NMDAr antagonists induce disturbances to gamma frequency oscillations, including increasing ongoing gamma activity and reducing evoked gamma oscillations. We sought to investigate the role parvalbumin (PV+) neurons and CaMKIIα+ pyramidal cells in NMDAr antagonist-induced disturbances in gamma oscillatory activity and relate these to common behavioural consequences of these drugs by selectively deleting the obligatory GluN1 subunit from these cells in mice. METHODS Adult mice (total n = 99) with GluN1 deleted from PV interneurons (PV:GluN1 KO) or CaMKIIα+ pyramidal cells (CaMKIIα:GluN1 KO), and WT littermates, were used. We assessed effects of the NMDAr antagonist MK-801 on prepulse inhibition (PPI) and locomotor behaviour. Then, mice were implanted with electrodes in the prefrontal cortex (mPFC) and hippocampus (dHPC), and the effects of MK-801 on gamma oscillations assessed. RESULTS In WT mice, MK-801 increased ongoing gamma power, reduced evoked gamma power and increased gamma coherence. These changes were accompanied by hyperlocomotion and deficient PPI. The consequences of NMDAr antagonism were differentially regulated in the transgenic mice. The MK-801-induced increase in ongoing gamma power was significantly attenuated in both transgenic strains, but deficits to evoked gamma activity were unaffected by genotype. Deficient PPI was not affected by genotype, and only in PV:GluN1 KO mice was the hyperlocomotor phenotype of MK-801 attenuated. The emergence of abnormal gamma band hyperconnectivity between the mPFC and dHPC was absent in CaMKIIα:GluN1 KO mice. CONCLUSION This study suggests that the effects of NMDAr antagonism on gamma band responses and behaviour have complex relationships, and rely on different populations of neurons.

中文翻译：

---

小白蛋白阳性中枢神经元和锥体神经元上的NMDA受体均促成MK-801诱发的伽马振荡障碍：与行为的复杂关系。

背景技术NMDAr拮抗剂诱导对伽马频率振荡的干扰，包括增加正在进行的伽马活性和减少诱发的伽马振荡。我们试图研究小白蛋白（PV +）神经元和CaMKIIα+锥体细胞在NMDAr拮抗剂诱导的伽马振荡活动障碍中的作用，并通过从小鼠这些细胞中选择性删除必需的GluN1亚基，将它们与这些药物的常见行为后果相关联。方法使用成年小鼠（总数n = 99），其中缺失了PV中间神经元（PV：GluN1 KO）或CaMKIIα+锥体细胞（CaMKIIα：GluN1 KO）中的GluN1，以及野生型同窝小鼠。我们评估了NMDAr拮抗剂MK-801对脉冲前抑制（PPI）和运动行为的影响。然后，在小鼠的前额叶皮层（mPFC）和海马（dHPC）中植入电极，并评估了MK-801对伽马振荡的影响。结果在野生型小鼠中，MK-801增加了持续的伽马射线能力，降低了诱发的伽马射线能力并增加了伽马射线相干性。这些变化伴有运动过度和PPI缺乏。NMDAr拮抗作用的结果在转基因小鼠中得到了不同的调控。在两种转基因菌株中，MK-801诱导的持续γ功率的增加均显着减弱，但是诱发的γ活性的缺陷不受基因型的影响。缺乏的PPI不受基因型的影响，只有在PV：GluN1 KO小鼠中，MK-801的超运动表型才被减弱。CaMKIIα：GluN1 KO小鼠中不存在mPFC和dHPC之间异常的伽马谱带超连通性的出现。