Cholinergic projections to the preBötzinger complex

Rhythmic inspiratory activity is generated in the preBötzinger complex (preBötC), a neuronal network located bilaterally in the ventrolateral medulla. Cholinergic neurotransmission affects respiratory rhythmogenic neurons and inhibitory glycinergic neurons in the preBötC. Acetylcholine has been exte...

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Bibliographic Details
Published in:	Journal of comparative neurology (1911) Vol. 531; no. 13; pp. 1317 - 1332
Main Authors:	Biancardi, Vivian, Yang, Xiaqiu, Ding, Xiuqing, Passi, Dhruv, Funk, Gregory D., Pagliardini, Silvia
Format:	Journal Article
Language:	English
Published:	United States Wiley Subscription Services, Inc 01-09-2023
Subjects:	Acetylcholine Acetyltransferase Animals breathing Choline O-acetyltransferase Cholinergic Agents Cholinergic Neurons - physiology cholinergic projections Glutamatergic transmission Medulla oblongata Medulla Oblongata - physiology Mice Mice, Transgenic Neural networks Neuromodulation Neurotransmission Pedunculopontine tegmental nucleus preBötzinger complex Recombinase Respiration Respiratory Center Reticular formation Sleep and wakefulness Solitary tract nucleus Transgenic mice viral tracing γ-Aminobutyric acid cholinergic projections preBötzinger complex breathing viral tracing
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Summary:	Rhythmic inspiratory activity is generated in the preBötzinger complex (preBötC), a neuronal network located bilaterally in the ventrolateral medulla. Cholinergic neurotransmission affects respiratory rhythmogenic neurons and inhibitory glycinergic neurons in the preBötC. Acetylcholine has been extensively investigated given that cholinergic fibers and receptors are present and functional in the preBötC, are important in sleep/wake cycling, and modulate inspiratory frequency through its action on preBötC neurons. Despite its role in modulating inspiratory rhythm, the source of acetylcholine input to the preBötC is not known. In the present study, we used retrograde and anterograde viral tracing approaches in transgenic mice expressing Cre‐recombinase driven by the choline acetyltransferase promoter to identify the source of cholinergic inputs to the preBötC. Surprisingly, we observed very few, if any, cholinergic projections originating from the laterodorsal and pedunculopontine tegmental nuclei (LDT/PPT), two main cholinergic, state‐dependent systems long hypothesized as the main source of cholinergic inputs to the preBötC. On the contrary, we identified glutamatergic and GABAergic/glycinergic neurons in the PPT/LDT that send projections to the preBötC. Although these neurons contribute minimally to the direct cholinergic modulation of preBötC neurons, they could be involved in state‐dependent regulation of breathing. Our data also suggest that the source of cholinergic inputs to the preBötC appears to originate from cholinergic neurons in neighboring regions of the medulla, the intermediate reticular formation, the lateral paragigantocellularis, and the nucleus of the solitary tract.
Bibliography:	Vivian Biancardi and Xiaqiu Yang contributed equally to this study. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0021-9967 1096-9861
DOI:	10.1002/cne.25497