Modulation of hypercapnic respiratory response by cholinergic transmission in the commissural nucleus of the solitary tract

Furuya, Werner I.; Bassi, Mirian; Menani, José Vanderlei; Colombari, Eduardo; Zoccal, Daniel B.; Colombari, Débora S. A.

doi:10.1007/s00424-019-02341-9

Cited by 5 publications

(2 citation statements)

References 58 publications

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“…Another source of cholinergic input was localized in the NTS. This is an important relay station for all visceral afferents and the coordination of chemoreflex, baroreflex, and cardiorespiratory responses (Furuya et al., 2020). Sparse cholinergic NTS neurons have been identified, but their function has not been established (Garfield et al., 2012; Maley, 1996).…”

Section: Discussionmentioning

confidence: 99%

Cholinergic projections to the preBötzinger complex

Biancardi,

Yang,

Ding

et al. 2023

J of Comparative Neurology

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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.

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Section: Discussionmentioning

confidence: 99%

Cholinergic projections to the preBötzinger complex

Biancardi,

Yang,

Ding

et al. 2023

J of Comparative Neurology

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“…The cholinergic system is involved in respiratory control, including central chemosensitivity, state-dependent modulation of breathing, and respiratory motor output [ 34 , 35 , 36 , 37 ]. The retrotrapezoid nucleus (RTN) contributing to chemical respiratory drive (CO 2 /H + ) [ 38 ] receives cholinergic input from the post-inspiratory complex (PiCO) and pedunculopontine tegmental nucleus (PPTg), and stimulation of PPTg has been shown to increase respiratory activity, in part, by cholinergic activation of chemosensitive RTN [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Hypoxic and Hypercapnic Responses in Transgenic Murine Model of Alzheimer’s Disease Overexpressing Human AβPP: The Effects of Pretreatment with Memantine and Rivastigmine

Andrzejewski

Jampolska

Mojzych

et al. 2022

IJMS

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Despite the severe respiratory problems reducing the quality of life for Alzheimer’s disease (AD) patients, their causes are poorly understood. We aimed to investigate hypoxic and hypercapnic respiratory responses in a transgenic mouse model of AD (AβPP V717I) overexpressing AβPP and mimicking early-onset AD. The cholinesterase inhibitor rivastigmine and the NMDA receptor antagonist memantine were used to investigate the effects of drugs, used to treat AD cognitive dysfunction, on breathing in hypoxia and hypercapnia. We found a significant increase in the respiratory response to hypercapnia and no difference in the hypoxic response in APP+ mice, compared with the control group (APP−). Memantine had no effect on respiration in either group, including responses to hypoxia and hypercapnia. Rivastigmine depressed resting ventilation and response to hypercapnia irrespective of the mice genotype. Reduction in hypoxia-augmented ventilation by rivastigmine was observed only in APP+ mice, which exhibited lower acetylcholinesterase activity in the hippocampus. Treatment with rivastigmine reduced the enzyme activity in both groups equally in the hippocampus and brainstem. The increased ventilatory response to hypercapnia in transgenic mice may indicate alterations in chemoreceptive respiratory nuclei, resulting in increased CO2 sensitivity. Rivastigmine is a potent reductant of normoxic and hypercapnic respiration in APP+ and APP− mice.

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