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Single dose of amphetamine induces delayed subregional attenuation of striatal cholinergic interneuron activity

View ORCID ProfileSamira Ztaou, Soo Jung Oh, Sophia Tepler, Sixtine Fleury, View ORCID ProfileMiriam Matamales, View ORCID ProfileJesus Bertran-Gonzalez, View ORCID ProfileNao Chuhma, View ORCID ProfileStephen Rayport
doi: https://doi.org/10.1101/2021.03.22.436417
Samira Ztaou
1Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA
2Department of Psychiatry, Columbia University, New York, NY 10032, USA
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  • ORCID record for Samira Ztaou
  • For correspondence: samira.ztaou@nyspi.columbia.edu stephen.rayport@nyspi.columbia.edu
Soo Jung Oh
1Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA
2Department of Psychiatry, Columbia University, New York, NY 10032, USA
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Sophia Tepler
1Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA
2Department of Psychiatry, Columbia University, New York, NY 10032, USA
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Sixtine Fleury
1Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA
2Department of Psychiatry, Columbia University, New York, NY 10032, USA
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Miriam Matamales
3Decision Neuroscience Laboratory, School of Psychology, University of New South Wales, Sydney, NSW, Australia
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  • ORCID record for Miriam Matamales
Jesus Bertran-Gonzalez
3Decision Neuroscience Laboratory, School of Psychology, University of New South Wales, Sydney, NSW, Australia
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  • ORCID record for Jesus Bertran-Gonzalez
Nao Chuhma
1Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA
2Department of Psychiatry, Columbia University, New York, NY 10032, USA
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Stephen Rayport
1Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA
2Department of Psychiatry, Columbia University, New York, NY 10032, USA
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  • For correspondence: samira.ztaou@nyspi.columbia.edu stephen.rayport@nyspi.columbia.edu
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Abstract

Psychostimulants such as amphetamine target dopamine neuron synapses to engender drug-induced plasticity. While dopamine neurons modulate the activity of striatal cholinergic interneurons (ChIs) with regional heterogeneity, how amphetamine affects ChI activity has not been elucidated. Here, we applied quantitative fluorescence imaging approaches to map the dose-dependent effects of a single dose of amphetamine on ChI activity at 2.5 and 24 hours after injection across the mouse striatum using the activity-dependent marker phosphorylated ribosomal protein S6 (p-rpS6). We found that amphetamine did not induce neurotoxic effects on ChIs, as their distribution and morphology were not affected. While low- or high-dose amphetamine did not affect ChI activity after 2.5 hours, ChI activity was significantly reduced in all striatal subregions after 24 hours, with a dose-dependent effect in the nucleus accumbens. Thus, our findings suggest that a single dose of amphetamine has delayed regionally heterogeneous effects on ChI activity.

Significance statement Using the activity dependent marker phosphorylated ribosomal protein S6 (p-rpS6), we mapped amphetamine effects on the activity of cholinergic interneurons (ChIs) across the striatum. Amphetamine caused a delayed attenuation of ChI activity in all striatal subregions, and a dose-dependent effect in the ventral striatum/nucleus accumbens, a critical site of psychostimulant action.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Conflict of interest The authors declare no competing financial interests.

Copyright 
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 March 22, 2021.
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Single dose of amphetamine induces delayed subregional attenuation of striatal cholinergic interneuron activity
Samira Ztaou, Soo Jung Oh, Sophia Tepler, Sixtine Fleury, Miriam Matamales, Jesus Bertran-Gonzalez, Nao Chuhma, Stephen Rayport
bioRxiv 2021.03.22.436417; doi: https://doi.org/10.1101/2021.03.22.436417
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Single dose of amphetamine induces delayed subregional attenuation of striatal cholinergic interneuron activity
Samira Ztaou, Soo Jung Oh, Sophia Tepler, Sixtine Fleury, Miriam Matamales, Jesus Bertran-Gonzalez, Nao Chuhma, Stephen Rayport
bioRxiv 2021.03.22.436417; doi: https://doi.org/10.1101/2021.03.22.436417

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