Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Institute of Anatomy II, Medical Faculty, Heinrich-Heine-University, Düsseldorf 40225, Germany.
Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Cell Rep. 2022 May 17;39(7):110822. doi: 10.1016/j.celrep.2022.110822.
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.
Cajal-Retzius 细胞对海马回路及其相关行为的调节作用尚未明确。在此，我们通过条件性敲除 vGluT2（其主要囊泡谷氨酸转运蛋白）来削弱 Cajal-Retzius 细胞的谷氨酸能输出，从而直接解决这一问题。尽管两种不同的条件性敲除系并未显示出海马层组织和主要神经元或 GABA 能细胞的树突长度有明显改变，但我们发现特定的海马依赖行为及其潜在的微回路存在平行缺陷。首先，条件性敲除动物表现出先天焦虑增加和齿状回颗粒细胞上的前馈 GABA 抑制减少。其次，我们观察到空间记忆处理受损，这与在穿通和内嗅-海马通路上的突触后反应的棘突密度降低以及 AMPA/NMDA 比值降低有关。我们得出结论，Cajal-Retzius 细胞释放的谷氨酸突触对于海马微回路和特定类型行为的调节至关重要。
