Developmental nicotine exposure blunts hyperthermia-induced excitation of hypoglossal motoneurons

Heat stress and developmental nicotine exposure (DNE) are both risk factors for sudden infant death syndrome. We aimed to evaluate the relationship between hyperthermia, DNE and the intrinsic properties of motoneurons involved in the control of breathing and swallowing. We hypothesized that hypoglossal motoneurons would demonstrate heat sensitivity, and that DNE would disrupt the neuronal response to hyperthermia. Thin brainstem slices were obtained from 4 control and 4 DNE neonatal rats aged 1-4 days (2 of each sex per group). During whole-cell patch clamp recordings, an automatic temperature controller was used to adjust the temperature of perfused artificial cerebrospinal fluid. Each experiment began at a bath temperature of 23° C and increased monotonically to 43°over ten minutes. Heat was then removed, and recordings continued until temperature returned to baseline. In cells from control animals, membrane potential (Vm) remained unchanged (-56 ± 9 mV) from 23-37°. From 38°, Vm steadily depolarized to -30 ± 15 mV at 43°. At high heat, all control motoneurons fired spontaneous action potentials prior to a persistent refractory period. After removal of heat, Vm and firing behavior recovered to baseline range in all control motoneurons. Conversely, in DNE motoneurons, heat evoked a steady membrane hyperpolarization from -60 ± 5 mV at 23° to -74 ± 7 mV at 40°, and -63 ± 4 mV at 43°. Still, all DNE motoneurons were refractory to firing at high heat. On return to normothermic conditions, Vm remained hyperpolarized (-67 ± 8 mV), and firing occurred across a truncated current range. The results suggest that during typical development, hypoglossal motoneurons are both sensitive and resilient to heat. We hypothesize that during severe heat stress, depolarization of respiratory motoneurons results in transiently increased excitability, which may facilitate the ventilatory response to hyperthermia. In contrast, motoneurons from DNE animals became hyperpolarized at high temperatures and were functionally less resilient. Interestingly, hypoglossal motoneurons in the thin slice preparation receive no input from the hypothalamus or respiratory pattern generator, suggesting that hypoglossal motoneurons are intrinsically heat sensitive. In summary, DNE significantly affects the heat sensitivity of hypoglossal motoneurons, which may impair both respiration and temperature regulation in the context of fever or environmental heat stress. This work was funded by NIH grants 5R01DC020889-02 and T32HL007249. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.