NPAS4 recruits CCK basket cell synapses and enhances cannabinoid-sensitive inhibition in the mouse hippocampus

Elife. 2018 Jul 27;7:e35927. doi: 10.7554/eLife.35927.


Experience-dependent expression of immediate-early gene transcription factors (IEG-TFs) can transiently change the transcriptome of active neurons and initiate persistent changes in cellular function. However, the impact of IEG-TFs on circuit connectivity and function is poorly understood. We investigate the specificity with which the IEG-TF NPAS4 governs experience-dependent changes in inhibitory synaptic input onto CA1 pyramidal neurons (PNs). We show that novel sensory experience selectively enhances somatic inhibition mediated by cholecystokinin-expressing basket cells (CCKBCs) in an NPAS4-dependent manner. NPAS4 specifically increases the number of synapses made onto PNs by individual CCKBCs without altering synaptic properties. Additionally, we find that sensory experience-driven NPAS4 expression enhances depolarization-induced suppression of inhibition (DSI), a short-term form of cannabinoid-mediated plasticity expressed at CCKBC synapses. Our results indicate that CCKBC inputs are a major target of the NPAS4-dependent transcriptional program in PNs and that NPAS4 is an important regulator of plasticity mediated by endogenous cannabinoids.

Keywords: CA1 pyramidal neuron; CCK basket cell; DSI; NPAS4; immediate early gene transcription factor; mouse; neuroscience.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • CA1 Region, Hippocampal / cytology
  • Cannabinoids / pharmacology*
  • Cell Differentiation / drug effects
  • Cholecystokinin / metabolism*
  • Hippocampus / cytology*
  • Interneurons / drug effects
  • Interneurons / metabolism
  • Mice, Inbred C57BL
  • Neural Inhibition / drug effects*
  • Parvalbumins / metabolism
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / physiology
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synaptic Transmission / drug effects


  • Basic Helix-Loop-Helix Transcription Factors
  • Cannabinoids
  • Npas4 protein, mouse
  • Parvalbumins
  • Cholecystokinin

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.