NMDA Receptor-Dependent Synaptic Potentiation via APPL1 Signaling Is Required for the Accessibility of a Prefrontal Neuronal Assembly in Retrieving Fear Extinction.

BACKGROUND: The ventromedial prefrontal cortex has been viewed as a locus for storage and recall of extinction memory. However, the synaptic and cellular mechanisms underlying these processes remain elusive. METHODS: We combined transgenic mice, electrophysiological recording, activity-dependent cell labeling, and chemogenetic manipulation to analyze the role of adaptor protein APPL1 in the ventromedial prefrontal cortex in fear extinction retrieval. RESULTS: We found that both constitutive and conditional APPL1 knockout decreased NMDA receptor (NMDAR) function in the ventromedial prefrontal cortex and impaired fear extinction retrieval. Moreover, APPL1 undergoes nuclear translocation during extinction retrieval. Blocking APPL1 nucleocytoplasmic translocation reduced NMDAR currents and disrupted extinction retrieval. We also identified a prefrontal neuronal ensemble that is both necessary and sufficient for the storage of extinction memory. Inducible APPL1 knockout in this ensemble abolished NMDAR-dependent synaptic potentiation and disrupted extinction retrieval, while chemogenetic activation of this ensemble simultaneously rescued the impaired behaviors. CONCLUSIONS: Our results indicate that a prefrontal neuronal ensemble stores extinction memory, and APPL1 signaling supports these neurons in retrieving extinction memory by controlling NMDAR-dependent potentiation.

[Spatiotemporal Change and Source Apportionment of Non-point Source Nitrogen and Phosphorus Pollution Loads in the Three Gorges Reservoir Area].

The Three Gorges Reservoir area (TGRA) is a critical water source protection area in China and one of the regions with rapid economic development in the Yangtze River basin. Non-point source pollution is the leading cause of the deterioration of the water environment in the TGRA; therefore, studying the non-point source pollution status in the TGRA is of great significance to the regional ecological security and sustainable development. The improved export coefficient model was used to estimate the total non-point source nitrogen and phosphorus pollution loads in the TGRA from 1990 to 2015, the spatial and temporal characteristics of the non-point source nitrogen and phosphorus pollution were analyzed, and the primary sources of pollution were determined by calculating the contribution rate of each pollution source. The results concluded that the nitrogen and phosphorus pollution loads were highest in the hinterland of the reservoir, followed by the end of the reservoir, with the lowest in the head of the reservoir, showing significant spatial heterogeneity in the TGRA. The total loads of nitrogen and phosphorus pollution increased firstly and then decreased, which reached the highest value in 2000 and the lowest value in 2015. The contribution rate of each pollution source to the nitrogen and phosphorus pollution loads, from highest to lowest, were land use, rural life, livestock, and poultry farming. Among them, the land use type of dry land was the predominant source of non-point source nitrogen and phosphorus pollution.