1. Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory Consolidation.
- Author
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De Rossi P, Nomura T, Andrew RJ, Masse NY, Sampathkumar V, Musial TF, Sudwarts A, Recupero AJ, Le Metayer T, Hansen MT, Shim HN, Krause SV, Freedman DJ, Bindokas VP, Kasthuri N, Nicholson DA, Contractor A, and Thinakaran G
- Subjects
- Animals, Brain metabolism, Excitatory Postsynaptic Potentials, Mice, Inbred C57BL, Mice, Knockout, Neurons ultrastructure, Presynaptic Terminals ultrastructure, Recognition, Psychology, SNARE Proteins metabolism, Spatial Learning, Adaptor Proteins, Signal Transducing metabolism, Memory Consolidation, Nerve Tissue Proteins metabolism, Neurons metabolism, Neurotransmitter Agents metabolism, Presynaptic Terminals metabolism, Tumor Suppressor Proteins metabolism
- Abstract
BIN1, a member of the BAR adaptor protein family, is a significant late-onset Alzheimer disease risk factor. Here, we investigate BIN1 function in the brain using conditional knockout (cKO) models. Loss of neuronal Bin1 expression results in the select impairment of spatial learning and memory. Examination of hippocampal CA1 excitatory synapses reveals a deficit in presynaptic release probability and slower depletion of neurotransmitters during repetitive stimulation, suggesting altered vesicle dynamics in Bin1 cKO mice. Super-resolution and immunoelectron microscopy localizes BIN1 to presynaptic sites in excitatory synapses. Bin1 cKO significantly reduces synapse density and alters presynaptic active zone protein cluster formation. Finally, 3D electron microscopy reconstruction analysis uncovers a significant increase in docked and reserve pools of synaptic vesicles at hippocampal synapses in Bin1 cKO mice. Our results demonstrate a non-redundant role for BIN1 in presynaptic regulation, thus providing significant insights into the fundamental function of BIN1 in synaptic physiology relevant to Alzheimer disease., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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