Reelin restricts dendritic growth of interneurons in the neocortex

Mohammad I.K. Hamad, Petya Petrova, Solieman Daoud, Obada Rabaya, Abdalrahim Jbara, Nesrine Melliti, Jennifer Leifeld, Igor Jakovčevski, Gebhard Reiss, Joachim Herz, Eckart Förster

Research output: Contribution to journalArticlepeer-review

Abstract

Reelin is a large secreted glycoprotein that regulates neuronal migration, lamination and establishment of dendritic architecture in the embryonic brain. Reelin expression switches postnatally from Cajal-Retzius cells to interneurons. However, reelin function in interneuron development is still poorly understood. Here, we have investigated the role of reelin in interneuron development in the postnatal neocortex. To preclude early cortical migration defects caused by reelin deficiency, we employed a conditional reelin knockout (RelncKO) mouse to induce postnatal reelin deficiency. Induced reelin deficiency caused dendritic hypertrophy in distal dendritic segments of neuropeptide Y-positive (NPY+) and calretinin-positive (Calr+) interneurons, and in proximal dendritic segments of parvalbumin-positive (Parv+) interneurons. Chronic recombinant Reelin treatment rescued dendritic hypertrophy in Relncko interneurons. Moreover, we provide evidence that RelncKO interneuron hypertrophy is due to presynaptic GABABR dysfunction. Thus, GABABRs in RelncKO interneurons were unable to block N-type (Cav2.2) Ca2+ channels that control neurotransmitter release. Consequently, the excessive Ca2+ influx through AMPA receptors, but not NMDA receptors, caused interneuron dendritic hypertrophy. These findings suggest that reelin acts as a 'stop-growth-signal' for postnatal interneuron maturation.

Original languageEnglish (US)
Article numbere199718
JournalDevelopment (Cambridge)
Volume148
Issue number17
DOIs
StatePublished - Sep 2021

Keywords

  • Dendritic growth
  • GABARs
  • Interneurons
  • Neocortex
  • Postnatal development
  • Reelin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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