| First Author | Biancardi V | Year | 2023 |
| Journal | J Comp Neurol | Volume | 531 |
| Issue | 13 | Pages | 1317-1332 |
| PubMed ID | 37211631 | Mgi Jnum | J:347484 |
| Mgi Id | MGI:7512714 | Doi | 10.1002/cne.25497 |
| Citation | Biancardi V, et al. (2023) Cholinergic projections to the preBotzinger complex. J Comp Neurol 531(13):1317-1332 |
| abstractText | Rhythmic inspiratory activity is generated in the preBotzinger complex (preBotC), a neuronal network located bilaterally in the ventrolateral medulla. Cholinergic neurotransmission affects respiratory rhythmogenic neurons and inhibitory glycinergic neurons in the preBotC. Acetylcholine has been extensively investigated given that cholinergic fibers and receptors are present and functional in the preBotC, are important in sleep/wake cycling, and modulate inspiratory frequency through its action on preBotC neurons. Despite its role in modulating inspiratory rhythm, the source of acetylcholine input to the preBotC 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 preBotC. 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 preBotC. On the contrary, we identified glutamatergic and GABAergic/glycinergic neurons in the PPT/LDT that send projections to the preBotC. Although these neurons contribute minimally to the direct cholinergic modulation of preBotC neurons, they could be involved in state-dependent regulation of breathing. Our data also suggest that the source of cholinergic inputs to the preBotC 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. |
