Inhibition of glutamatergic interneurons of the lateral parafacial region of mice attenuates the ventilatory response to hypercapnia

• DOI: 10.1152/physiol.2024.39.s1.648
• Publication Date: 2024-05-21T14:57:50Z
• Authors: Juliana Reis Souza; Nathalia Salim; Renato Willian Ma...; Benedito Honorio ...; Davi José de Alme...
• Keywords: 0301 basic medicine; 03 medical and health sciences

The lateral parafacial region (pF L ) generates the expiratory motor activity during hypercapnia. It was demonstrated that this contains excitatory neurons and interneurons (with local projections), with a population of glutamatergic are silent under resting conditions, but become active at end expiration, simultaneously in response to hypercapnia/acidosis. However, role pF regulating pulmonary ventilation hypercapnia is unclear. Herein, we hypothesized inhibition attenuates ventilatory responses Therefore, evaluated effects chemogenetic non-anesthetized mice on parameters We used genetically modified expressing enzyme cre recombinase VGLUT2-positive (CEUA 1143/2022), injected unilaterally cre-dependent adeno-associated retrograde virus express FLP recombinase, followed by cre- FLP-dependent inhibitory Designer Receptors Exclusively Activated Drugs (hM4D-Gi) only interneurons. Using whole-body plethysmography, measured respiratory frequency (f R ), tidal volume (V T E duration cycle, inspiration (DI) expiration (DE) normocapnia (7% CO 2 after activating hM4D-Gi JHU 37160 (0.1 mg/kg; i.p.). Data expressed as mean ± standard deviation. By analyzing expression mCherry fluorescent protein, found significant number (68.22 11.7; n=18). At normocapnia, injection did not change VGLUT2 (cre/cre + hM4D-Gi) (n=18) (cre/cre) (n=12) [(ΔfR: -2.4±51 vs 0.2±48 cpm; p=0.88) (ΔVT: -1.3±4 -0.2±1 μL·g −1 ; p=0.39) (ΔVE: -39 ±1198 -71±607 ·min p=0.72) (ΔCycle duration: 5.3±41 -1.9±45 ms; p=0.65) (ΔDI: 6.6±14 6±20 p=0.92) (ΔDE: -1.3±35 -1.6±31 p=0.97)]. On other hand, attenuated hypercapnia-induced when compared (n=9) 67±69 157±41 p=0.0003) 3.8±5 11.9±4 p<0.0001) 2052±2197 5374±1773 (Δcycle -46±50 -107±49 p=0.002) -3.7±16 -21±19 p=0.011) -42±41 -86±36 p=0.01)]. In conclusion, our data demonstrate important for FAPESP, CNPq CAPES. This full abstract presented American Physiology Summit 2024 meeting available HTML format. There no additional versions or content abstract. involved peer review process.