Hartung Henrike, Cichon Nicole, De Feo Vito, Riemann Stephanie, Schildt Sandra, Lindemann Christoph, Mulert Christoph, Gogos Joseph A, Hanganu-Opatz Ileana L
Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Laboratory of Neurobiology, Department of Biosciences, University of Helsinki, 00014 Helsinki, Finland.
Cereb Cortex. 2016 Oct 17;26(11):4265-4281. doi: 10.1093/cercor/bhw274.
Cognitive deficits represent a major burden of neuropsychiatric disorders and result in part from abnormal communication within hippocampal-prefrontal circuits. While it has been hypothesized that this network dysfunction arises during development, long before the first clinical symptoms, experimental evidence is still missing. Here, we show that pre-juvenile mice mimicking genetic and environmental risk factors of disease (dual-hit GE mice) have poorer recognition memory that correlates with augmented coupling by synchrony and stronger directed interactions between prefrontal cortex and hippocampus. The network dysfunction emerges already during neonatal development, yet it initially consists in a diminished hippocampal theta drive and consequently, a weaker and disorganized entrainment of local prefrontal circuits in discontinuous oscillatory activity in dual-hit GE mice when compared with controls. Thus, impaired maturation of functional communication within hippocampal-prefrontal networks switching from hypo- to hyper-coupling may represent a mechanism underlying the pathophysiology of cognitive deficits in neuropsychiatric disorders.
认知缺陷是神经精神疾病的主要负担，部分原因是海马-前额叶回路内的异常通信。虽然有人假设这种网络功能障碍在发育过程中就已出现，远早于首次临床症状，但仍缺乏实验证据。在这里，我们表明，模拟疾病遗传和环境风险因素的幼年前期小鼠（双打击GE小鼠）具有较差的识别记忆，这与同步增强耦合以及前额叶皮层和海马之间更强的定向相互作用相关。网络功能障碍在新生儿发育期间就已出现，但最初表现为海马θ驱动减弱，因此，与对照组相比，双打击GE小鼠在不连续振荡活动中局部前额叶回路的夹带更弱且紊乱。因此，海马-前额叶网络内从低耦合到高耦合的功能性通信成熟受损可能是神经精神疾病认知缺陷病理生理学的潜在机制。
