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Erschienen in: Brain Structure and Function 6/2021

16.05.2021 | Original Article

Characterization of basal forebrain glutamate neurons suggests a role in control of arousal and avoidance behavior

verfasst von: James T. McKenna, Chun Yang, Thomas Bellio, Marissa B. Anderson-Chernishof, Mackenzie C. Gamble, Abigail Hulverson, John G. McCoy, Stuart Winston, Erik Hodges, Fumi Katsuki, James M. McNally, Radhika Basheer, Ritchie E. Brown

Erschienen in: Brain Structure and Function | Ausgabe 6/2021

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Abstract

The basal forebrain (BF) is involved in arousal, attention, and reward processing but the role of individual BF neuronal subtypes is still being uncovered. Glutamatergic neurons are the least well-understood of the three main BF neurotransmitter phenotypes. Here we analyzed the distribution, size, calcium-binding protein content and projections of the major group of BF glutamatergic neurons expressing the vesicular glutamate transporter subtype 2 (vGluT2) and tested the functional effect of activating them. Mice expressing Cre recombinase under the control of the vGluT2 promoter were crossed with a reporter strain expressing the red fluorescent protein, tdTomato, to generate vGluT2-cre-tdTomato mice. Immunohistochemical staining for choline acetyltransferase and a cross with mice expressing green fluorescent protein selectively in GABAergic neurons confirmed that cholinergic, GABAergic and vGluT2+ neurons represent distinct BF subpopulations. Subsets of BF vGluT2+ neurons expressed the calcium-binding proteins calbindin or calretinin, suggesting that multiple subtypes of BF vGluT2+ neurons exist. Anterograde tracing using adeno-associated viral vectors expressing channelrhodopsin2-enhanced yellow fluorescent fusion proteins revealed major projections of BF vGluT2+ neurons to neighboring BF cholinergic and parvalbumin neurons, as well as to extra-BF areas involved in the control of arousal or aversive/rewarding behavior such as the lateral habenula and ventral tegmental area. Optogenetic activation of BF vGluT2+ neurons elicited a striking avoidance of the area where stimulation was given, whereas stimulation of BF parvalbumin or cholinergic neurons did not. Together with previous optogenetic findings suggesting an arousal-promoting role, our findings suggest that BF vGluT2 neurons play a dual role in promoting wakefulness and avoidance behavior.
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Metadaten
Titel
Characterization of basal forebrain glutamate neurons suggests a role in control of arousal and avoidance behavior
verfasst von
James T. McKenna
Chun Yang
Thomas Bellio
Marissa B. Anderson-Chernishof
Mackenzie C. Gamble
Abigail Hulverson
John G. McCoy
Stuart Winston
Erik Hodges
Fumi Katsuki
James M. McNally
Radhika Basheer
Ritchie E. Brown
Publikationsdatum
16.05.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
Brain Structure and Function / Ausgabe 6/2021
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI
https://doi.org/10.1007/s00429-021-02288-7

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