Morphology, input–output relations and synaptic connectivity of Cajal–Retzius cells in layer 1 of the developing neocortex of CXCR4-EGFP mice

Max Anstotz, Kathleen E. Cosgrove, Iris Hack, Enrico Mugnaini, Gianmaria Maccaferri, Joachim H.R. Lübke*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Layer 1 (L1) neurons, in particular Cajal–Retzius (CR) cells are among the earliest generated neurons in the neocortex. However, their role and that of L1 GABAergic interneurons in the establishment of an early cortical microcircuit are still poorly understood. Thus, the morphology of whole-cell recorded and biocytin-filled CR cells was investigated in postnatal day (P) 7–11 old CXCR4-EGFP mice where CR cells can be easily identified by their fluorescent appearance. Confocal-, light- and subsequent electron microscopy was performed to investigate their developmental regulation, morphology, synaptic input–output relationships and electrophysiological properties. CR cells reached their peak in occurrence between P4 to P7 and from thereon declined to almost complete disappearance at P14 by undergoing selective cell death through apoptosis. CR cells formed a dense and long-range horizontal network in layer 1 with a remarkable high density of synaptic boutons along their axons. They received dense GABAergic and non-GABAergic synaptic input and in turn provided synaptic output preferentially with spines or shafts of terminal tuft dendrites of pyramidal neurons. Interestingly, no dye-coupling between CR cells with other cortical neurons was observed as reported for other species, however, biocytin-labeling of individual CR cells leads to co-staining of L1 end foot astrocytes. Electrophysiologically, CR cells are characterized by a high input resistance and a characteristic firing pattern. Increasing depolarizing currents lead to action potential of decreasing amplitude and increasing half width, often terminated by a depolarization block. The presence of membrane excitability, the high density of CR cells in layer 1, their long-range horizontal axonal projection together with a high density of synaptic boutons and their synaptic input–output relationship suggest that they are an integral part of an early cortical network important not only in layer 1 but also for the establishment and formation of the cortical column.

Original languageEnglish (US)
Pages (from-to)2119-2139
Number of pages21
JournalBrain Structure and Function
Issue number6
StatePublished - Nov 1 2014


  • CXCR4-EGFP mice
  • Cajal–Retzius cells
  • GABAergic interneurons
  • Input–output synapses
  • Long-range horizontal axons
  • Neocortical layer 1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Anatomy
  • Histology


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