Investigating Cardiovascular Sensory Afferent Pathways to Adrenergic Groups

Abstract

Cardiovascular autonomic reflexes arise from activation of peripheral glutamatergic sensory inputs terminating in brainstem’s nucleus of the solitary tract (NTS). NTS neurons process, integrate and encode information for descending neuronal groups, ultimately resulting in a homeostatic response. However, anatomical and circuit-based genetic mapping data supports distinct circuits beginning in NTS for individual sensory information. Additionally, other brain regions projecting to cardiovascular regulatory regions modify these cardiovascular homeostatic responses. In particular, central adrenergic regions send axonal projections not only to NTS, but also major cardiovascular regulatory regions throughout brainstem. Therefore, we hypothesized that activation of baroreflex or cardiopulmonary chemoreflex results in differential inhibition of a neuronal activity marker, c-Fos, production in adrenergic brain regions. To examine this, chemical stimulation of transient receptor potential vanilloid subtype 1 receptors (TRPV1) using capsaicin (5 ug/ml) or baroreceptors using phenylephrine (PE; 25 ug/ml) was performed in adult male and female mice using jugular catheterization under urethane anesthesia. After 90 minutes, mice were transcardially perfused and brain slices were processed for c-Fos and tyrosine hydroxylase (TH) immunoreactivity. As expected, PE and capsaicin both elicited significant bradycardia (PE: -362±24 bpm, capsaicin: -482.25±11 bpm) compared to controls (n=4 and p<0.0001 all groups). Immunohistochemical analysis of A2 found no significant differences in total TH+ neurons (PE: 22±1; capsaicin: 26±4; controls: 23±3). However, the percent of TH+ neurons labeled with c-Fos after injection of PE was significantly lower (8±3) than the precent of c-Fos+ TH neurons after capsaicin (19±3; p=0.05) or controls (17±1; p=0.04). A2 did not demonstrate a significant difference in c-Fos expression between capsaicin and controls (p=0.9). Examination of locus coeruleus (LC) found no significant difference in total TH+ neurons (PE: 37±4; capsaicin: 43±6; controls: 39±5). In contrast to A2, LC demonstrated a significant difference in c-Fos immunoreactivity after capsaicin. Specifically, the percent of TH+ neurons labeled with c-Fos after injection of capsaicin was significantly lower (36±3) than the percent of c-Fos+ TH neurons after PE (54±6; p=0.05) or controls (56±6; p=0.04). These data indicate that activation of baroreflex elicits a significant inhibition of c-Fos production in A2, while activation of cardiopulmonary chemoreflex elicits a significant inhibition of c-Fos in LC. Therefore, in relation to adrenergic brain regions, these data provide evidence for divergence in circuits related to these two sensory inputs. Future studies will address other reflexes, but more importantly will determine specific circuits responsible for communication of sensory input to these adrenergic brain regions. NIH R01HL157366 to CRB This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.