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Cholinergic interneurons mediate cocaine extinction through similar plasticity across medium spiny neuron subtypes

View ORCID ProfileWeston Fleming, Junuk Lee, View ORCID ProfileBrandy A. Briones, Scott Bolkan, View ORCID ProfileIlana B. Witten
doi: https://doi.org/10.1101/2021.08.29.458113
Weston Fleming
1Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey, USA
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Junuk Lee
1Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey, USA
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Brandy A. Briones
1Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey, USA
2Department of Psychology, Princeton University, Princeton, New Jersey, USA
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Scott Bolkan
1Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey, USA
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Ilana B. Witten
1Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey, USA
2Department of Psychology, Princeton University, Princeton, New Jersey, USA
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  • For correspondence: iwitten@princeton.edu
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Abstract

Cholinergic interneurons (ChINs) in the nucleus accumbens (NAc) have been implicated in the acquisition and extinction of drug associations, as well as related plasticity in medium spiny neurons (MSNs). However, since most previous work has relied on artificial manipulations, if and how endogenous patterns of cholinergic signaling relate to drug associations is unknown. Moreover, despite great interest in the opposing effects of dopamine on MSN subtypes, whether ChIN-mediated effects are similar or different across MSN subtypes is also unknown. Here, we find that endogenous acetylcholine event frequency during extinction negatively correlates with the strength and persistence of cocaine-context associations across individuals, consistent with effects of artificial manipulation of ChIN activity during extinction. Moreover, ChIN activation during extinction produces a reduction in excitatory synaptic strength on both MSN subtypes, similar to the effect of multiple extinction sessions in the absence of ChIN manipulations. Together, our findings indicate that natural variation in NAc acetylcholine may contribute to individual differences in drug-context extinction by modulating glutamatergic presynaptic strength similarly at both D1R and D2R MSN subtypes.

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Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 29, 2021.
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Cholinergic interneurons mediate cocaine extinction through similar plasticity across medium spiny neuron subtypes
Weston Fleming, Junuk Lee, Brandy A. Briones, Scott Bolkan, Ilana B. Witten
bioRxiv 2021.08.29.458113; doi: https://doi.org/10.1101/2021.08.29.458113
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Cholinergic interneurons mediate cocaine extinction through similar plasticity across medium spiny neuron subtypes
Weston Fleming, Junuk Lee, Brandy A. Briones, Scott Bolkan, Ilana B. Witten
bioRxiv 2021.08.29.458113; doi: https://doi.org/10.1101/2021.08.29.458113

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