Sex‐specific consequences of neonatal stress on laryngeal chemoreflex stimulation in rat pups: Contribution of excitatory currents onto key brainstem regions

Abstract

In preterm infants and rat pups, the presence of liquids or solids in the airways stimulates the laryngeal chemoreflex (LCR) which results in prolonged apneas, O2 desaturations, and bradycardias with life threatening consequences. We previously showed that neonatal stress interferes with respiratory control development and aggravates the bradycardias evoked by LCR stimulation. Here, we addressed underlying mechanisms by testing the hypothesis that neonatal stress augments synaptic inputs converging onto the vagal motor nucleus (NX), a key brainstem region regulating heart rate. Experiments were performed on 14‐15 days old pups that were either undisturbed (controls) or subjected to neonatal maternal separation (NMS; 3h/day from P3 to P12). Because the impact of NMS is greater in males, experiments were performed on pups from both sexes. Brainstem slices from the obex area were obtained and whole‐cell voltage clamp recordings were performed on single NX neurons. Miniature EPSCs were revealed by TTX application. The frequency and amplitude of spontaneous and miniature EPSCs were measured. NMS augments the frequency but not the amplitude of spontaneous EPSCs. TTX application reduced the frequency and amplitude of currents. These effects were greater in NMS rats but did not differ between sexes. This suggests that NMS increases the activity level of incoming excitatory inputs to NX neurons. We conclude that in NMS pups, the increase in excitatory inputs converging onto the vagal motor nucleus contribute to the augmented bradycardia following LCR stimulation; however, the lack of sexual dimorphism in these effects suggest that other mechanisms and/or structures are responsible for sex‐specific effects of NMS on the LCR.