Laboratory of molecular psychiatry, Department of psychiatry, University of Münster, Germany.
Laboratory of molecular psychiatry, Department of psychiatry, University of Münster, Germany.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Aug 30;94:109658. doi: 10.1016/j.pnpbp.2019.109658. Epub 2019 May 27.
The prefrontal cortex (PFC) is a center for executive and cognitive functions. Although many studies have been carried out to elucidate the role of different subtypes of GABAergic neurons in other brain areas, their functional relevance in PFC is still not fully understood. Calretinin-GABAergic neurons are heterogeneous in their morphology and intrinsic properties. Previous studies showed an involvement of CR-GABAergic neurons in the disinhibition of the other GABAergic neurons in neocortex and hippocampus. Furthermore, the loss of CR- and PV-interneurons in human brain has been linked to the vulnerability of the interneurons and to the overall increase in the network excitability associated with mental diseases. In the present study, the intensity of CR-neuropil was higher in layer II/III, whereas the intensity of PV-neuropil was higher in deeper layers within the PFC. In addition, pronounced CR expression was detected in layer II and III of prelimbic and infralimbic cortex whereas they were less abundant in anterior cingulate cortex and motor cortex 2. Our results showed that bipolar CR- neurons in layer V not only feedback inhibited multipolar CR- and other interneurons in layer II/III, but the majority of bipolar CR-neurons in layer II/III also provide long-range forward-inhibition to pyramidal neurons in deeper layers of PFC. Thus, given the importance of the neuronal network of PFC in central control of emotion and cognition and in the pathology of mental diseases, CR-GABAergic neuron-mediated feed-forward and -backward modulation within PFC would differentially modulate the downstream limbic activity and subsequently shape the cognitive and emotional behavior.
前额叶皮层（PFC）是执行和认知功能的中心。尽管已经进行了许多研究来阐明其他脑区不同亚型 GABA 能神经元的作用，但它们在 PFC 中的功能相关性仍未完全理解。钙结合蛋白-GABA 能神经元在形态和内在特性上是异质的。先前的研究表明，CR-GABA 能神经元参与了新皮层和海马体中其他 GABA 能神经元的去抑制作用。此外，人类大脑中 CR 和 PV 中间神经元的丧失与中间神经元的易损性以及与精神疾病相关的网络兴奋性的整体增加有关。在本研究中，CR 神经突的强度在 II/III 层更高，而 PV 神经突的强度在 PFC 的更深层更高。此外，在边缘前皮质和边缘下皮质的 II 和 III 层检测到明显的 CR 表达，而在前扣带皮质和运动皮质 2 中则较少。我们的结果表明，V 层中的双极 CR 神经元不仅反馈抑制 II/III 层中的多极 CR 和其他中间神经元，而且 II/III 层中的大多数双极 CR 神经元也对 PFC 更深层的锥体神经元提供长程前馈抑制。因此，鉴于 PFC 的神经元网络在情绪和认知的中枢控制以及精神疾病的病理学中的重要性，CR-GABA 能神经元介导的 PFC 内的前馈和反馈调节将差异调节下游边缘活动，并随后塑造认知和情绪行为。
