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Cholinergic control of striatal GABAergic microcircuits

S. Kocaturk, F. Shah, B. Guven, J.M. Tepper, M. Assous
doi: https://doi.org/10.1101/2021.11.22.469580
S. Kocaturk
Center for Molecular and Behavioral Neuroscience, Rutgers, the State University of New Jersey 197 University Avenue Newark, NJ 07102 USA
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F. Shah
Center for Molecular and Behavioral Neuroscience, Rutgers, the State University of New Jersey 197 University Avenue Newark, NJ 07102 USA
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B. Guven
Center for Molecular and Behavioral Neuroscience, Rutgers, the State University of New Jersey 197 University Avenue Newark, NJ 07102 USA
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J.M. Tepper
Center for Molecular and Behavioral Neuroscience, Rutgers, the State University of New Jersey 197 University Avenue Newark, NJ 07102 USA
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M. Assous
Center for Molecular and Behavioral Neuroscience, Rutgers, the State University of New Jersey 197 University Avenue Newark, NJ 07102 USA
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  • For correspondence: assous.maxime@gmail.com
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Abstract

Cholinergic interneurons (CINs) are essential elements of striatal circuits and behaviors. While acetylcholine signaling via muscarinic receptors (mAChRs) have been well studied, more recent data indicate that postsynaptic nicotinic receptors (nAChRs) located on GABAergic interneurons (GINs) are equally critical. One demonstration is that CINs stimulation induces large disynaptic inhibition of SPNs mediated by nAChR activation of striatal GINs. While these circuits are ideally positioned to modulate striatal output activity, the neurons involved are not definitively identified due largely to an incomplete mapping of CINs-GINs interconnections. Here, we show that CINs optogenetic activation evokes an intricate dual mechanism involving co-activation of pre- and postsynaptic mAChRs and nAChRs on four GINs populations. Using multi-optogenetics, we demonstrate the participation of tyrosine hydroxylase-expressing GINs in the disynaptic inhibition of SPNs likely via heterotypic electrical coupling with neurogliaform interneurons. Altogether, our results highlight the importance of CINs in regulating GINs microcircuits via complex synaptic/heterosynaptic mechanisms.

Competing Interest Statement

The authors have declared no competing interest.

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 November 23, 2021.
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Cholinergic control of striatal GABAergic microcircuits
S. Kocaturk, F. Shah, B. Guven, J.M. Tepper, M. Assous
bioRxiv 2021.11.22.469580; doi: https://doi.org/10.1101/2021.11.22.469580
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Cholinergic control of striatal GABAergic microcircuits
S. Kocaturk, F. Shah, B. Guven, J.M. Tepper, M. Assous
bioRxiv 2021.11.22.469580; doi: https://doi.org/10.1101/2021.11.22.469580

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