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.

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Highlights ▪ At the Paris climate negotiations in 2015, countries agreed to establish 2020 as a key milestone in the global effort to fight climate change. As part of the regular five-year cycles to strengthen ambition laid out in the Paris Agreement, countries are requested to put forward nationally determined contributions (NDCs) by 2020. ▪ The rationale for updating NDCs, and particularly for enhancing mitigation ambition, is greater than ever: The latest climate science underscores the need for ambitious, immediate action to keep the Paris Agreement goals within reach; technological advances increasingly facilitate ambitious action; and the alignment between ambitious climate action and socioeconomic benefits is increasingly well documented and understood. ▪ This guidance provides a structure to help countries think through the process of enhancing their NDCs along three dimensions: mitigation, adaptation, and transparent communication. ▪ With regard to mitigation, this guidance places a priority on enhancing ambition and reducing emissions to achieve the temperature goals in the Paris Agreement, while noting that NDCs can also be enhanced to strengthen implementation in various ways. ▪ Enhancing an adaptation component of an NDC depends strongly on a country's objectives with regard to adaptation and the relationship between the NDC and other adaptation-related processes.