Glutamate released by Cajal-Retzius cells impacts specific hippocampal circuits and behaviors.

Glutamate released by Cajal-Retzius cells impacts specific hippocampal circuits and behaviors.
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DOI:
10.1016/j.celrep.2022.110822
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发表时间:
2022-05-17
期刊:
影响因子:
8.8
通讯作者:
Maccaferri, Gianmaria
Maccaferri, Gianmaria
中科院分区:
生物学1区
文献类型:
--
作者:
Anstoz, Max;Lee, Sun Kyong;Maccaferri, Gianmaria

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Cajal-Retzius细胞对海马回路和相关行为的调节的影响尚未得到解决。在这里,我们直接解决这个问题,通过损害的vGluT 2,这是他们的主要囊泡谷氨酸转运蛋白的条件消融的Cajal-Retzius细胞的谷氨酸能输出。虽然两个不同的条件性基因敲除线没有揭示主要神经元或GABA能细胞的树突层组织和树突长度的重大改变,我们发现在特定的树突依赖的行为,并在其假定的基础微电路平行赤字。首先,条件性基因敲除动物表现出先天性焦虑增加和对齿状回颗粒细胞的前馈GABA能抑制减少。其次,我们观察到受损的空间记忆处理,这是与减少脊椎密度和减少的AMPA/NMDA比率的突触后反应在perforant和内鼻海马通路。我们的结论是谷氨酸释放的Cajal-Retzius细胞突触是至关重要的海马微电路和特定类型的行为的调节。Anstötz等人报告称,出生后海马Cajal-Retzius细胞使用vGluT 2作为其主要的谷氨酸囊泡转运蛋白。vGluT 2在小鼠中的条件性失活揭示了行为和网络的改变。观察到的结果表明,Cajal-Retzius细胞参与先天性焦虑/空间记忆的调节和潜在相关的神经元回路。
The impact of Cajal-Retzius cells on the regulation of hippocampal circuits and related behaviors is unresolved. Here, we directly address this issue by impairing the glutamatergic output of Cajal-Retzius cells with the conditional ablation of vGluT2, which is their main vesicular glutamate transporter. Although two distinct conditional knockout lines do not reveal major alterations in hippocampal-layer organization and dendritic length of principal neurons or GABAergic cells, we find parallel deficits in specific hippocampal-dependent behaviors and in their putative underlying microcircuits. First, conditional knockout animals show increased innate anxiety and decreased feedforward GABAergic inhibition on dentate gyrus granule cells. Second, we observe impaired spatial memory processing, which is associated with decreased spine density and reduced AMPA/NMDA ratio of postsynaptic responses at the perforant- and entorhino-hippocampal pathways. We conclude that glutamate synaptically released by Cajal-Retzius cells is critical for the regulation of hippocampal microcircuits and specific types of behaviors. Anstötz et al. report that postnatal hippocampal Cajal-Retzius cells use vGluT2 as their main glutamate vesicular transporter. Conditional inactivation of vGluT2 in mice reveals both behavioral and network alterations. The observed results indicate the involvement of Cajal-Retzius cells in the regulation of innate anxiety/spatial memory and in potentially related neuronal circuits.
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