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

Max Anstötz*, Sun Kyong Lee, Gianmaria Maccaferri*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish (US)
Article number110822
JournalCell reports
Issue number7
StatePublished - May 17 2022


  • CP: Neuroscience
  • anxiety
  • development
  • interneuron
  • memory
  • optogenetics
  • spine
  • transporter

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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