Npas4 recruits CCK basket cell synapses and enhances cannabinoid-sensitive inhibition in the mouse hippocampus
- University of California, San Diego, United States
Abstract
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.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Brenda L Bloodgood
Funding
Pew Charitable Trusts (28631)
- Brenda L Bloodgood
Kinship Foundation (14-SSP-184)
- Brenda L Bloodgood
Whitehall Foundation (2013-12-88)
- Brenda L Bloodgood
National Science Foundation (2013154395)
- Andrea L Hartzell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations and guidance provided by the Research Compliance and Integrity Program and the Institutional Animal Care and Use Committee (IACUC) at UC San Diego. All of the animals were handled according to the approved IACUC protocol, S12254, of UC San Diego. All surgeries and euthanasia were performed under deep isoflurane anesthesia, and every effort was made to minimize suffering.
Copyright
© 2018, Hartzell et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Npas4 recruits CCK basket cell synapses and enhances cannabinoid-sensitive inhibition in the mouse hippocampus
eLife 7:e35927.
https://doi.org/10.7554/eLife.35927
