Centre for Ageing Dementia Research, The University of Queensland, Brisbane, QLD, 4072, Australia.
Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia.
Transl Psychiatry. 2018 Sep 21;8(1):199. doi: 10.1038/s41398-018-0248-x.
Cholinergic basal forebrain (cBF)-derived neurotransmission plays a crucial role in regulating neuronal function throughout the cortex, yet the mechanisms controlling cholinergic innervation to downstream targets have not been elucidated. Here we report that removing the p75 neurotrophin receptor (p75) from cBF neurons induces a significant impairment in fear extinction consolidation. We demonstrate that this is achieved through alterations in synaptic connectivity and functional activity within the medial prefrontal cortex. These deficits revert back to wild-type levels upon re-expression of the active domain of p75 in adult animals. These findings demonstrate a novel role for cholinergic neurons in fear extinction consolidation and suggest that neurotrophic signaling is a key regulator of cholinergic-cortical innervation and function.
胆碱能基底前脑 (cBF) 衍生的神经递质在调节整个皮层的神经元功能方面起着至关重要的作用，但控制胆碱能神经支配下游靶标的机制尚未阐明。在这里，我们报告说，从 cBF 神经元中去除 p75 神经营养因子受体 (p75) 会导致恐惧消退巩固显著受损。我们证明，这是通过改变内侧前额叶皮层内的突触连接和功能活动来实现的。在成年动物中重新表达 p75 的活性结构域后，这些缺陷恢复到野生型水平。这些发现表明胆碱能神经元在恐惧消退巩固中具有新的作用，并表明神经营养信号是胆碱能-皮层神经支配和功能的关键调节剂。
