Response of the respiratory network of mice to hyperthermia

Most mammals modulate respiratory frequency (RF) to dissipate heat (i.e., panting) and avoid heat stroke during hyperthermic conditions. During hyperthermia, the RF of intact mammals increases and then declines or ceases (apnea). It has been proposed that this RF modulation depends on the presence of higher brain structures such as the hypothalamus. However, the direct effects of hyperthermia on the respiratory neural network have not been examined. To address this issue, the respiratory neural network [i.e., ventral respiratory group (VRG)] was isolated in a brain stem preparation taken from the medulla of mice (P0 -P6). Integrated population activity, predominated by inspiratory neurons, was recorded extracellularly from VRG neurons. The bath temperature was then heated from 30 to 40 degrees C, resulting in a biphasic frequency response in VRG activity. Following an initial six- to sevenfold increase and subsequent decline, fictive RF was maintained at a frequency that was higher than baseline frequency; at 40 degrees C, the RF was maintained at about two to four times that at 30 degrees C. The inspiratory burst amplitude and duration were significantly reduced during hyperthermic conditions. An increase in RF and decrease in VRG burst amplitude and duration also occurred when heating from 37 to 40 degrees C. Fictive apnea typically occurred during cooling to the control temperature. Furthermore, changes in hypoglossal motor nucleus activity paralleled those of the VRG, suggesting that temperature modulation of the VRG is likely to have a behaviorally relevant impact on respiration. We conclude that the VRG activity itself is modulated during hyperthermia and the respiratory network is particularly sensitive to temperature changes.