Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling

Jay A. Blundon; Noah C. Roy; Brett J.W. Teubner; Jing Yu; Tae Yeon Eom; K. Jake Sample; Amar Pani; Richard J. Smeyne; Seung Baek Han; Ryan A. Kerekes; Derek C. Rose; Troy A. Hackett; Pradeep K. Vuppala; Burgess B. Freeman; Stanislav S. Zakharenko

doi:10.1126/science.aaf4612

Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling

Jay A. Blundon, Noah C. Roy, Brett J.W. Teubner, Jing Yu, Tae Yeon Eom, K. Jake Sample, Amar Pani, Richard J. Smeyne, Seung Baek Han, Ryan A. Kerekes, Derek C. Rose, Troy A. Hackett, Pradeep K. Vuppala, Burgess B. Freeman, Stanislav S. Zakharenko

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

Circuits in the auditory cortex are highly susceptible to acoustic influences during an early postnatal critical period. The auditory cortex selectively expands neural representations of enriched acoustic stimuli, a process important for human language acquisition. Adults lack this plasticity. Here we show in the murine auditory cortex that juvenile plasticity can be reestablished in adulthood if acoustic stimuli are paired with disruption of ecto-5′-nucleotidase-dependent adenosine production or A₁-adenosine receptor signaling in the auditory thalamus. This plasticity occurs at the level of cortical maps and individual neurons in the auditory cortex of awake adult mice and is associated with long-term improvement of tone-discrimination abilities. We conclude that, in adult mice, disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.

Original language	English
Pages (from-to)	1352-1356
Number of pages	5
Journal	Science
Volume	356
Issue number	6345
DOIs	https://doi.org/10.1126/science.aaf4612
State	Published - Jun 30 2017

Funding

This work was supported by NIH grants DC012833, MH097742 (S.S.Z.), and DC015388 (T.A.H.), and by American Lebanese Syrian Associated Charities (ALSAC) (S.S.Z.). The funding sources had no role in the study design, data collection, data analysis, decision to publish, or preparation of the manuscript. We thank the Vector Core Laboratories (St. Jude Children's Research Hospital and University of Tennessee Health Science Center) and J. Westmoreland for assistance in producing AAVs and lentiviruses; F. Du for assistance in generating Adora1fl/fl mice and pharmacokinetic studies; J. Min and A. Mayasundari for help with FR194921; A. Onar-Thomas for statistical assistance; A. Uptain and K. Anderson for assistance with imaging experiments and viral injections in vivo; and V. Shanker and A. McArthur for editing the manuscript. The supplementary materials contain additional data. S.S.Z. and J.A.B. are inventors on patent application PCT/US2016/018377 submitted by St. Jude Children's Research Hospital, which covers the subject of improved learning through inhibition of adenosine signaling in the thalamus.

Funders	Funder number
National Institutes of Health	DC012833, MH097742
National Institute on Deafness and Other Communication Disorders	R01DC015388
Health Science Center, University of Tennessee	FR194921
St. Jude Children's Research Hospital
American Lebanese Syrian Associated Charities

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Blundon, J. A., Roy, N. C., Teubner, B. J. W., Yu, J., Eom, T. Y., Sample, K. J., Pani, A., Smeyne, R. J., Han, S. B., Kerekes, R. A., Rose, D. C., Hackett, T. A., Vuppala, P. K., Freeman, B. B., & Zakharenko, S. S. (2017). Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling. Science, 356(6345), 1352-1356. https://doi.org/10.1126/science.aaf4612

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abstract = "Circuits in the auditory cortex are highly susceptible to acoustic influences during an early postnatal critical period. The auditory cortex selectively expands neural representations of enriched acoustic stimuli, a process important for human language acquisition. Adults lack this plasticity. Here we show in the murine auditory cortex that juvenile plasticity can be reestablished in adulthood if acoustic stimuli are paired with disruption of ecto-5′-nucleotidase-dependent adenosine production or A1-adenosine receptor signaling in the auditory thalamus. This plasticity occurs at the level of cortical maps and individual neurons in the auditory cortex of awake adult mice and is associated with long-term improvement of tone-discrimination abilities. We conclude that, in adult mice, disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.",

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AU - Blundon, Jay A.

AU - Roy, Noah C.

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AU - Yu, Jing

AU - Eom, Tae Yeon

AU - Sample, K. Jake

AU - Pani, Amar

AU - Smeyne, Richard J.

AU - Han, Seung Baek

AU - Kerekes, Ryan A.

AU - Rose, Derek C.

AU - Hackett, Troy A.

AU - Vuppala, Pradeep K.

AU - Freeman, Burgess B.

AU - Zakharenko, Stanislav S.

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AB - Circuits in the auditory cortex are highly susceptible to acoustic influences during an early postnatal critical period. The auditory cortex selectively expands neural representations of enriched acoustic stimuli, a process important for human language acquisition. Adults lack this plasticity. Here we show in the murine auditory cortex that juvenile plasticity can be reestablished in adulthood if acoustic stimuli are paired with disruption of ecto-5′-nucleotidase-dependent adenosine production or A1-adenosine receptor signaling in the auditory thalamus. This plasticity occurs at the level of cortical maps and individual neurons in the auditory cortex of awake adult mice and is associated with long-term improvement of tone-discrimination abilities. We conclude that, in adult mice, disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.

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ER -

Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling

Abstract

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