Characterization of basal forebrain glutamate neurons suggests a role in control of arousal and avoidance behavior
| Autor: | Radhika Basheer, Stuart Winston, Fumi Katsuki, Marissa B Anderson-Chernishof, Ritchie E. Brown, James T. McKenna, James M. McNally, Chun Yang, Mackenzie C. Gamble, Abigail Hulverson, Thomas Bellio, John G. McCoy, Erik L. Hodges |
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| Rok vydání: | 2021 |
| Předmět: |
Histology
Basal Forebrain Cholinergic Agents Glutamic Acid Optogenetics Biology Nucleus basalis Article 050105 experimental psychology Mice 03 medical and health sciences 0302 clinical medicine Avoidance Learning medicine Animals 0501 psychology and cognitive sciences Wakefulness Cholinergic neuron Basal forebrain General Neuroscience 05 social sciences Choline acetyltransferase Cholinergic Neurons Ventral tegmental area Parvalbumins medicine.anatomical_structure nervous system Vesicular Glutamate Transport Protein 2 biology.protein Cholinergic Anatomy Neuroscience 030217 neurology & neurosurgery Parvalbumin |
| Zdroj: | Brain Struct Funct |
| ISSN: | 1863-2661 1863-2653 |
| DOI: | 10.1007/s00429-021-02288-7 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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