Bidirectional signaling of neuregulin-2 mediates formation of GABAergic synapses and maturation of glutamatergic synapses in newborn granule cells of postnatal hippocampus

Kyu Hee Lee, Hyunsu Lee, Che Ho Yang, Jeong Soon Ko, Chang Hwan Park, Ran Sook Woo, Joo Yeon Kim, Woong Sun, Joung Hun Kim, Won Kyung Ho, Suk Ho Lee

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Expression of neuregulin-2 (NRG2) is intense in a few regions of the adult brain where neurogenesis persists; however, little is understood about its role in developments of newborn neurons. To study the role of NRG2 in synaptogenesis at different developmental stages, newborn granule cells in rat hippocampal slice cultures were labeled with retrovirus encoding tetracycline-inducible microRNA targeting NRG2 and treated with doxycycline (Dox) at the fourth or seventh postinfection day (dpi). The developmental increase of GABAergic postsynaptic currents (GPSCs) was suppressed by the early Dox treatment (4 dpi), but not by late treatment (7 dpi). The late Dox treatment was used to study the effect of NRG2 depletion specific to excitatory synaptogenesis. The Dox effect on EPSCs emerged 4 d after the impairment in dendritic outgrowth became evident (10 dpi). Notably, Dox treatment abolished the developmental increases of AMPA-receptor mediated EPSCs and the AMPA/NMDA ratio, indicating impaired maturation of glutamatergic synapses. In contrast to GPSCs, Dox effects on EPSCs and dendritic growth were independent of ErbB4 and rescued by concurrent overexpression of NRG2 intracellular domain. These results suggest that forward signaling of NRG2 mediates GABAergic synaptogenesis and its reverse signaling contributes to dendritic outgrowth and maturation of glutamatergic synapses.

Original languageEnglish
Pages (from-to)16479-16493
Number of pages15
JournalJournal of Neuroscience
Volume35
Issue number50
DOIs
Publication statusPublished - 2015 Dec 16

Keywords

  • Dentate gyrus
  • ErbB4
  • Neuregulin
  • Neurogenesis
  • Synaptogenesis

ASJC Scopus subject areas

  • Neuroscience(all)

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