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.
Bibliographical noteFunding Information:
We thank Drs. Tim V. Bliss and Paul W. Frankland for feedback on an earlier draft of this paper, and Ms. Anushka Ahmad D’mello and Ms. Katarzyna Kita for help with experimental work. This work was supported by the UK Biotechnology and Biological Sciences Research Council to K.P.G. ( BB/J021423/1 ) and M.G.S. ( BB/J021687/1 ).
We thank Drs. Tim V. Bliss and Paul W. Frankland for feedback on an earlier draft of this paper, and Ms. Anushka Ahmad D'mello and Ms. Katarzyna Kita for help with experimental work. This work was supported by the UK Biotechnology and Biological Sciences Research Council to K.P.G. (BB/J021423/1) and M.G.S. (BB/J021687/1). W.A. I.K. M.G.S. and K.P.G. designed research. W.A. I.K. K.M. T.F. H.R. K.K. and S.R. performed the experiments. W.A. I.K. A.K. T.F. and F.J. analyzed the data. K.R. provided a lentivirus that was used in the earlier stages of the project. W.A. and K.P.G. wrote the manuscript. All authors reviewed the manuscript. The authors declare no competing interests.
© 2019 The Authors
- contextual fear conditioning
- memory storage
- multiinnervated dendritic spines
- normal aging
- structural plasticity at synapses
- synaptic signaling
ASJC Scopus subject areas
- Neuroscience (all)
- Biochemistry, Genetics and Molecular Biology (all)
- Agricultural and Biological Sciences (all)