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Published April 29, 2024 | in press
Journal Article Open

Unsupervised restoration of a complex learned behavior after large-scale neuronal perturbation

Abstract

Reliable execution of precise behaviors requires that brain circuits are resilient to variations in neuronal dynamics. Genetic perturbation of the majority of excitatory neurons in HVC, a brain region involved in song production, in adult songbirds with stereotypical songs triggered severe degradation of the song. The song fully recovered within 2 weeks, and substantial improvement occurred even when animals were prevented from singing during the recovery period, indicating that offline mechanisms enable recovery in an unsupervised manner. Song restoration was accompanied by increased excitatory synaptic input to neighboring, unmanipulated neurons in the same brain region. A model inspired by the behavioral and electrophysiological findings suggests that unsupervised single-cell and population-level homeostatic plasticity rules can support the functional restoration after large-scale disruption of networks that implement sequential dynamics. These observations suggest the existence of cellular and systems-level restorative mechanisms that ensure behavioral resilience.

Copyright and License

© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

Acknowledgement

This work was supported by National Institutes of Health grant R01 NS104925-01 (C.L. and A.L.F.). We thank R. Pang for contributing to the code used to run simulations. We thank F. Lagzi for valuable discussions. This work was facilitated through the use of advanced computational, storage and networking infrastructure provided by the Hyak supercomputer system and funded by the Student Technology Fee at the University of Washington.

Contributions

These authors contributed equally: Bo Wang, Zsofia Torok, Alison Duffy.

These authors jointly supervised this work: Tarciso A. F. Velho, Adrienne L. Fairhall, Carlos Lois.

All authors contributed to the conceptualization, methodology, and writing of the paper. Experimental investigations were undertaken by B.W., Z.T., S.W., T.A.F.V. and C.L. Computational investigations were carried out by A.D. and D.G.B. Visualization was performed by B.W., A.D. and D.G.B. Funding acquisition and supervision was done by A.L.F. and C.L.

Data Availability

All derived data in this study are included in this article. Raw datasets are publicly available online at https://doi.org/10.22002/dvhsa-h5s72 (ref. 72) or by contacting the corresponding authors. Source data are provided with this paper.

Extended Data Fig. 1 Specific infection of HVC projection neurons by LVs.

Extended Data Fig. 2 Expression of NaChBac in HVC(RA) neurons.

Extended Data Fig. 3 Expressing TeNT in HVC(RA) cells blocked their synaptic output.

Extended Data Fig. 4 Songs degradation and recovery was not due to mechanical lesion or inflammation.

Extended Data Fig. 5 Recovery of fine intra-syllable structure without practice.

Extended Data Fig. 6 Recovery of syllable durations without practice.

Extended Data Fig. 7 Unperturbed cells did not change their intrinsic excitability or inhibitory synaptic inputs.

Extended Data Fig. 8 Synaptic changes in unmanipulated neurons only occurred in the injected hemisphere.

Extended Data Fig. 9 Recovery of modeled sequences with STDP.

Extended Data Fig. 10 Recovery of modeled sequences with population-level homeostatic plasticity.

Supplementary Figs. 1–7

Supplementary Audio 1

Supplementary Audio 2

Supplementary Audio 3

Supplementary Audio 4

Supplementary Audio 5

Supplementary Audio 6

Source Data Fig. 2

Source Data Fig. 4

Source Data Fig. 5

Source Data Extended Data Fig. 2/Table 2

Source Data Extended Data Fig. 3/Table 3

Source Data Extended Data Fig. 7/Table 7

Source Data Extended Data Fig. 8/Table 8

Code Availability

Custom codes associated with this study are publicly available (for behavior analysis, https://doi.org/10.5281/zenodo.10823142 (ref. 73); for modeling, code is available on GitHub at https://github.com/davidgbe/unsupervised_restoration_modeling (ref. 74) and on Zenodo at https://doi.org/10.5281/zenodo.10823218 (ref. 75)).

Conflict of Interest

The authors declare no competing interests.

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Additional details

Created:
May 3, 2024
Modified:
May 3, 2024