Specific Disruption of Hippocampal Mossy Fiber Synapses in a Mouse Model of Familial Alzheimers DiseaseReport as inadecuate




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The earliest stages of Alzheimer-s disease AD are characterized by deficits in memory and cognition indicating hippocampal pathology. While it is now recognized that synapse dysfunction precedes the hallmark pathological findings of AD, it is unclear if specific hippocampal synapses are particularly vulnerable. Since the mossy fiber MF synapse between dentate gyrus DG and CA3 regions underlies critical functions disrupted in AD, we utilized serial block-face electron microscopy SBEM to analyze MF microcircuitry in a mouse model of familial Alzheimer-s disease FAD. FAD mutant MF terminal complexes were severely disrupted compared to control – they were smaller, contacted fewer postsynaptic spines and had greater numbers of presynaptic filopodial processes. Multi-headed CA3 dendritic spines in the FAD mutant condition were reduced in complexity and had significantly smaller sites of synaptic contact. Significantly, there was no change in the volume of classical dendritic spines at neighboring inputs to CA3 neurons suggesting input-specific defects in the early course of AD related pathology. These data indicate a specific vulnerability of the DG-CA3 network in AD pathogenesis and demonstrate the utility of SBEM to assess circuit specific alterations in mouse models of human disease.



Author: Scott A. Wilke, Tara Raam, Joseph K. Antonios, Eric A. Bushong, Edward H. Koo, Mark H. Ellisman, Anirvan Ghosh

Source: http://plos.srce.hr/



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