Filopodia are a structural substrate for silent synapses in adult neocortex

Dimitra Vardalaki, Kwanghun Chung, Mark T. Harnett

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Newly generated excitatory synapses in the mammalian cortex lack sufficient AMPA-type glutamate receptors to mediate neurotransmission, resulting in functionally silent synapses that require activity-dependent plasticity to mature. Silent synapses are abundant in early development, during which they mediate circuit formation and refinement, but they are thought to be scarce in adulthood1. However, adults retain a capacity for neural plasticity and flexible learning that suggests that the formation of new connections is still prevalent. Here we used super-resolution protein imaging to visualize synaptic proteins at 2,234 synapses from layer 5 pyramidal neurons in the primary visual cortex of adult mice. Unexpectedly, about 25% of these synapses lack AMPA receptors. These putative silent synapses were located at the tips of thin dendritic protrusions, known as filopodia, which were more abundant by an order of magnitude than previously believed (comprising about 30% of all dendritic protrusions). Physiological experiments revealed that filopodia do indeed lack AMPA-receptor-mediated transmission, but they exhibit NMDA-receptor-mediated synaptic transmission. We further showed that functionally silent synapses on filopodia can be unsilenced through Hebbian plasticity, recruiting new active connections into a neuron’s input matrix. These results challenge the model that functional connectivity is largely fixed in the adult cortex and demonstrate a new mechanism for flexible control of synaptic wiring that expands the learning capabilities of the mature brain.

Original languageEnglish
Pages (from-to)323-327
Number of pages5
Issue number7939
Publication statusPublished - 2022 Dec 8

Bibliographical note

Funding Information:
We thank D. H. Yun for technical assistance with eMAP, K. Tsimring and A. Krol for technical assistance with perfusions, and C. Yaeger, M. Tadross, E. Nedivi and M. Bear for constructive criticism of the manuscript. We thank H. Umemori for the donation of Thy1-GFP-M+ mouse pups. Financial support was provided by the Boehringer Ingelheim Fonds (D.V.), National Institutes of Health RO1NS106031 (M.T.H.), the James W. and Patricia T. Poitras Fund at MIT (M.T.H.), a Klingenstein-Simons Fellowship (M.T.H.), a Vallee Foundation Scholarship (M.T.H.) and a McKnight Scholarship (M.T.H.).

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

All Science Journal Classification (ASJC) codes

  • General


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