Neuronal BIN1 Regulates Presynaptic Neurotransmitter Release and Memory Consolidation

Cell Rep. 2020 Mar 10;30(10):3520-3535.e7. doi: 10.1016/j.celrep.2020.02.026.


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.

Keywords: 3D EM reconstruction; Amphiphysin 2; BIN1; Morris water maze; STED; dSTORM; late-onset Alzheimer disease; release probability; super-resolution; synaptic physiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Brain / metabolism
  • Excitatory Postsynaptic Potentials
  • Memory Consolidation*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Neurotransmitter Agents / metabolism*
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Recognition, Psychology
  • SNARE Proteins / metabolism
  • Spatial Learning
  • Tumor Suppressor Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Bin1 protein, mouse
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • SNARE Proteins
  • Tumor Suppressor Proteins