Guirado Ramon, Umemori Juzoh, Sipilä Pia, Castrén Eero
Neuroscience Center, University of Helsinki, Helsinki, Finland.
Neuroscience Center, University of Helsinki, Helsinki, Finland Current address: Max Planck Institute for Neurobiology, Martinsried, Germany.
Cereb Cortex. 2016 Mar;26(3):1287-94. doi: 10.1093/cercor/bhv280. Epub 2015 Dec 3.
Inputs to sensory cortices are known to compete for target innervation through an activity-dependent mechanism during critical periods. To investigate whether this principle also applies to association cortices such as the medial prefrontal cortex (mPFC), we produced a bilateral lesion during early development to the ventral hippocampus (vHC), an input to the mPFC, and analyzed the intensity of the projection from another input, the basolateral amgydala (BLA). We found that axons from the BLA had a higher density of "en passant" boutons in the mPFC of lesioned animals. Furthermore, the density of neurons labeled with retrograde tracers was increased, and neurons projecting from the BLA to the mPFC showed increased expression of FosB. Since neonatal ventral hippocampal lesion has been used as an animal model of schizophrenia, we investigated its effects on behavior and found a negative correlation between the density of retrogradely labeled neurons in the BLA and the reduction of the startle response in the prepulse inhibition test. Our results not only indicate that the inputs from the BLA and the vHC compete for target innervation in the mPFC during postnatal development but also that subsequent abnormal rewiring might underlie the pathophysiology of neuropsychiatric disorders such as schizophrenia.
已知在关键期，感觉皮层的输入通过一种活动依赖机制竞争靶神经支配。为了研究这一原理是否也适用于诸如内侧前额叶皮层（mPFC）这样的联合皮层，我们在发育早期对腹侧海马体（vHC，mPFC的一个输入）进行双侧损伤，并分析了来自另一个输入——基底外侧杏仁核（BLA）的投射强度。我们发现，在损伤动物的mPFC中，来自BLA的轴突具有更高密度的“沿途”终扣。此外，用逆行示踪剂标记的神经元密度增加，并且从BLA投射到mPFC的神经元显示FosB表达增加。由于新生期腹侧海马体损伤已被用作精神分裂症的动物模型，我们研究了其对行为的影响，发现在前脉冲抑制试验中，BLA中逆行标记神经元的密度与惊吓反应的降低之间存在负相关。我们的结果不仅表明在出生后发育过程中，来自BLA和vHC的输入在mPFC中竞争靶神经支配，而且后续异常的神经重新布线可能是精神分裂症等神经精神疾病病理生理学的基础。
