Multi-input Synapses, but Not LTP-Strengthened Synapses, Correlate with Hippocampal Memory Storage in Aged Mice

Wajeeha Aziz, Igor Kraev, Keiko Mizuno, Alastair Kirby, Ton Fang, Huzefa Rupawala, Kamillia Kasbi, Stephanie Rothe, Felix Jozsa, Kobi Rosenblum, Michael G. Stewart, K. Peter Giese

Research output: Contribution to journalArticlepeer-review


Long-lasting changes at synapses enable memory storage in the brain. Although aging is associated with impaired memory formation, it is not known whether the synaptic underpinnings of memory storage differ with age. Using a training schedule that results in the same behavioral memory formation in young and aged mice, we examined synapse ultrastructure and molecular signaling in the hippocampus after contextual fear conditioning. Only in young, but not old mice, contextual fear memory formation was associated with synaptic changes that characterize well-known, long-term potentiation, a strengthening of existing synapses with one input. Instead, old-age memory was correlated with generation of multi-innervated dendritic spines (MISs), which are predominantly two-input synapses formed by the attraction of an additional excitatory, presynaptic terminal onto an existing synapse. Accordingly, a blocker used to inhibit MIS generation impaired contextual fear memory only in old mice. Our results reveal how the synaptic basis of hippocampal memory storage changes with age and suggest that these distinct memory-storing mechanisms may explain impaired updating in old age.

Original languageEnglish
Pages (from-to)3600-3610.e4
JournalCurrent Biology
Issue number21
StatePublished - 4 Nov 2019

Bibliographical note

Publisher Copyright:
© 2019 The Authors


  • CaMKII
  • PSD-95
  • contextual fear conditioning
  • memory storage
  • multiinnervated dendritic spines
  • nNOS
  • normal aging
  • reconsolidation
  • structural plasticity at synapses
  • synaptic signaling

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences


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