Calretinin+-neurons-mediated GABAergic inhibition in mouse prefrontal cortex
Calretinin+-neurons-mediated GABAergic inhibition in mouse prefrontal cortex
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DOI：
10.1016/j.pnpbp.2019.109658
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发表时间：
2019-08-30
影响因子：
5.6
通讯作者：
Zhang, Weiqi
中科院分区：
文献类型：
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作者：
Saffari, Roja;Grotefeld, Kirsten;Zhang, Weiqi
前额叶皮层（PFC）是执行和认知功能的中心。尽管已经开展了许多研究来阐明gaba能神经元不同亚型在其他脑区中的作用，但它们在PFC中的功能相关性仍未完全了解。Calretinin(+)- 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中其他gaba能神经元的去抑制。此外，人类大脑中CR+和PV+中间神经元的缺失与中间神经元的易损性和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，在pfc内，CR+- neuropil的强度在层内较高，而PV+-neuropil的强度在更深层较高。此外，在边缘前皮层和边缘下皮层的第二层和第三层检测到明显的CR表达，而在前扣带皮层和运动皮质2中较少表达。我们的研究结果表明，V层的双极CR+-神经元不仅反馈抑制了II/III层的多极CR+-和其他中间神经元，而且II/III层的大多数双极CR+-神经元还对PFC更深层的锥体神经元提供了远距离正向抑制。因此，考虑到PFC神经元网络在情绪和认知中枢控制以及精神疾病病理中的重要性，在PFC内，CR+- gaba能神经元介导的前馈和后向调节会对下游边缘活动产生差异，从而形成认知和情绪行为。
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 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.