Abnormalities in Excitability of Nucleus Tractus Solitarius (nTS) Neurons Following Neonatal Hypoxia Exposure: Implications for Sudden Infant Death Syndrome

Abstract

We showed previously that the respiratory neural control system exhibits a heightened vulnerability to sustained hypoxia (SH) exposure during a critical period of postnatal development, specifically between postnatal (P) day 11–15. The vulnerability was associated with a loss of the acute hypoxic ventilatory response (HVR) and ~85% unexpected and unexplained mortality that occurred not during SH per se, but ~3 days later (P18). These effects of SH, combined with increased microglia and decreased serotonin (5‐HT) expression found uniquely within the nucleus tractus solitarius (nTS), are key characteristics of the brainstem abnormalities associated with sudden infant death syndrome (SIDS). In the current study, therefore, we investigated whether these effects of following SH exposure are associated with altered excitability of neurons in a site of the nTS associated with hypoxic chemoafferent integration. Rats were exposed to SH (10% O2, 24hrs/day) between P11–15. Control rats received normoxia (NX, 21% O2). We used whole‐cell patch clamp recordings to examine the excitatory properties of nTS neurons monosynaptically connected to the solitary tract in P18 rats i.e. 3 days post‐SH and at a time leading up to the anticipated day of mortality. SH exposure decreased the frequency (3.0 ± 0.6 Hz) of spontaneous EPSCs in nTS neurons compared to NX (6.9 ± 1.4 Hz) rats; rise time, decay time, and area of the spontaneous EPSC's did not differ between groups. The amplitude of evoked (0.5 and 10 Hz stimulus train) EPSCs in monosynaptically connected nTS neurons was increased in the SH group compared to NX after being corrected for cells size, which was also significantly decreased in the SH group. We speculate that the increased evoked responses of the nTS neurons following SH could be a form of homeostatic plasticity, representing an attempt to compensate for disturbances in chemoafferent inputs. Further, the decreased spontaneous activity of the nTS neurons could imply a significant disturbance in spontaneous neurotransmitter release, which appears to worsen leading up to the day that prior SH exposure manifests as neonatal mortality. These data reveal the changes that occur in brainstem neural control regions following neonatal SH exposure and could provide important insight into the (cardio)‐respiratory abnormalities of SIDS.