Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation

Feng Ju Weng, Rodrigo I. Garcia, Stefano Lutzu, Karina Alviña, Yuxiang Zhang, Margaret Dushko, Taeyun Ku, Khaled Zemoura, David Rich, Dario Garcia-Dominguez, Matthew Hung, Tushar D. Yelhekar, Andreas Toft Sørensen, Weifeng Xu, Kwanghun Chung, Pablo E. Castillo, Yingxi Lin

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Synaptic connections between hippocampal mossy fibers (MFs) and CA3 pyramidal neurons are essential for contextual memory encoding, but the molecular mechanisms regulating MF-CA3 synapses during memory formation and the exact nature of this regulation are poorly understood. Here we report that the activity-dependent transcription factor Npas4 selectively regulates the structure and strength of MF-CA3 synapses by restricting the number of their functional synaptic contacts without affecting the other synaptic inputs onto CA3 pyramidal neurons. Using an activity-dependent reporter, we identified CA3 pyramidal cells that were activated by contextual learning and found that MF inputs on these cells were selectively strengthened. Deletion of Npas4 prevented both contextual memory formation and this learning-induced synaptic modification. We further show that Npas4 regulates MF-CA3 synapses by controlling the expression of the polo-like kinase Plk2. Thus, Npas4 is a critical regulator of experience-dependent, structural, and functional plasticity at MF-CA3 synapses during contextual memory formation. Weng et al. report that the transcription factor Npas4 selectively regulates the number of functional synaptic contacts between CA3 pyramidal neurons and mossy fibers, allowing for learning-induced modification of MF-CA3 synapses during contextual memory formation.

Original languageEnglish (US)
Pages (from-to)1137-1152.e5
JournalNeuron
Volume97
Issue number5
DOIs
StatePublished - Mar 7 2018

Keywords

  • CA3
  • MF-CA3 synapses
  • Npas4
  • Plk2
  • RAM
  • active neuronal ensembles
  • contextual memory
  • neuronal activity
  • robust activity marking system

ASJC Scopus subject areas

  • Neuroscience(all)

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    Weng, F. J., Garcia, R. I., Lutzu, S., Alviña, K., Zhang, Y., Dushko, M., Ku, T., Zemoura, K., Rich, D., Garcia-Dominguez, D., Hung, M., Yelhekar, T. D., Sørensen, A. T., Xu, W., Chung, K., Castillo, P. E., & Lin, Y. (2018). Npas4 Is a Critical Regulator of Learning-Induced Plasticity at Mossy Fiber-CA3 Synapses during Contextual Memory Formation. Neuron, 97(5), 1137-1152.e5. https://doi.org/10.1016/j.neuron.2018.01.026