Dynamic ErbB4 Activity in Hippocampal-Prefrontal Synchrony and Top-Down Attention in Rodents

Neuron. 2018 Apr 18;98(2):380-393.e4. doi: 10.1016/j.neuron.2018.03.018. Epub 2018 Apr 5.


Top-down attention is crucial for meaningful behaviors and impaired in various mental disorders. However, its underpinning regulatory mechanisms are poorly understood. We demonstrate that the hippocampal-prefrontal synchrony associates with levels of top-down attention. Both attention and synchrony are reduced in mutant mice of ErbB4, a receptor of neuregulin-1. We used chemical genetic and optogenetic approaches to inactivate ErbB4 kinase and ErbB4+ interneurons, respectively, both of which reduce gamma-aminobutyric acid (GABA) activity. Such inhibitions in the hippocampus impair both hippocampal-prefrontal synchrony and top-down attention, whereas those in the prefrontal cortex alter attention, but not synchrony. These observations identify a role of ErbB4-dependent GABA activity in the hippocampus in synchronizing the hippocampal-prefrontal pathway and demonstrate that acute, dynamic ErbB4 signaling is required to command top-down attention. Because both neuregulin-1 and ErbB4 are susceptibility genes of schizophrenia and major depression, our study contributes to a better understanding of these disorders. VIDEO ABSTRACT.

Keywords: ADHD; E/I balance; ErbB4; GABA transmission; hippocampal-prefrontal synchrony; major depression; neuregulin-1; schizophrenia; top-down attention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention / physiology*
  • Cells, Cultured
  • Hippocampus / metabolism*
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Organ Culture Techniques
  • Prefrontal Cortex / metabolism*
  • Random Allocation
  • Reaction Time / physiology*
  • Receptor, ErbB-4 / genetics
  • Receptor, ErbB-4 / metabolism*
  • Rodentia
  • gamma-Aminobutyric Acid / genetics
  • gamma-Aminobutyric Acid / metabolism


  • gamma-Aminobutyric Acid
  • Erbb4 protein, mouse
  • Receptor, ErbB-4