Dentate Gyrus Local Circuit is Implicated in Learning Under Stress—a Role for Neurofascin

Femke M.P. Zitman, Morgan Lucas, Sabine Trinks, Laura Grosse-Ophoff, Martin Kriebel, Hansjürgen Volkmer, Gal Richter-Levin

Research output: Contribution to journalArticlepeer-review


The inhibitory synapses at the axon initial segment (AIS) of dentate gyrus granular cells are almost exclusively innervated by the axo-axonic chandelier interneurons. However, the role of chandelier neurons in local circuitry is poorly understood and controversially discussed. The cell adhesion molecule neurofascin is specifically expressed at the AIS. It is crucially required for the stabilization of axo-axonic synapses. Knockdown of neurofascin is therefore a convenient tool to interfere with chandelier input at the AIS of granular neurons of the dentate gyrus. In the current study, feedback and feedforward inhibition of granule cells was measured in the dentate gyrus after knockdown of neurofascin and concomitant reduction of axo-axonic input. Results show increased feedback inhibition as a result of neurofascin knockdown, while feedforward inhibition remained unaffected. This suggests that chandelier neurons are predominantly involved in feedback inhibition. Neurofascin knockdown rats also exhibited impaired learning under stress in the two-way shuttle avoidance task. Remarkably, this learning impairment was not accompanied by differences in electrophysiological measurements of dentate gyrus LTP. This indicates that the local circuit may be involved in (certain types) of learning.

Original languageEnglish
Pages (from-to)842-850
Number of pages9
JournalMolecular Neurobiology
Issue number2
StatePublished - 1 Mar 2016

Bibliographical note

Publisher Copyright:
© 2014, Springer Science+Business Media New York.


  • Axon initial segment (AIS)
  • GABA receptor clustering
  • Hippocampus
  • Learning impairment

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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