Cold stimulates the behavioral response to hypoxia in newborn mice

Abstract

In newborns, hypoxia elicits increased ventilation, arousal followed by defensive movements, and cries. Cold is known to affect the ventilatory response to hypoxia, but whether it affects the arousal response remains unknown. The aim of the present study was to assess the effects of cold on the ventilatory and arousal responses to hypoxia in newborn mice. We designed an original platform measuring noninvasively and simultaneously the breathing pattern by whole body plethysmography, body temperature by infrared thermography, as well as motor and ultrasonic vocal (USV) responses. Six-day-old mice were exposed twice to 10% O(2) for 3 min at either cold temperature (26 degrees C) or thermoneutrality (33 degrees C). At 33 degrees C, hypoxia elicited a marked increase in ventilation followed by a small ventilatory decline, small motor response, and almost no USVs. Body temperature was not influenced by hypoxia, and oxygen consumption (Vo(2)) displayed minimal changes. At 26 degrees C, hypoxia elicited a slight increase in ventilation with a large ventilatory decline and a large drop of Vo(2). This response was accompanied by marked USV and motor responses. Hypoxia elicited a small decrease in temperature after the return to normoxia, thus precluding any causal influence on the motor and USV responses to hypoxia. In conclusion, cold stimulated arousal and stress responses to hypoxia, while depressing hypoxic hyperpnea. Arousal is an important defense mechanism against sleep-disordered breathing. The dissociation between ventilatory and behavioral responses to hypoxia suggests that deficits in the arousal response associated with sleep breathing disorders cannot be attributed to a depressed hypoxic response.

Arousal from sleep in response to intermittent hypoxia in rat pups is modulated by medullary raphe GABAergic mechanisms

“…Variably, there is a startle response. Although ultrasonic vocalizations have been described in young rodents in response to hypoxia, these do not occur when hypoxia is introduced during thermoneutrality (9). Because all of our studies were performed in a thermoneutral environment, we elected to rely solely on stereotypical behavior to identify arousal to wakefulness.…”

Impaired ventilatory and thermoregulatory responses to hypoxic stress in newborn Phox2b heterozygous knock-out mice

“…Similarly, HVD was assessed as the maximal decrease of V E in response to hypoxia. We previously reported that V E started to decrease during hypoxia, about 90 s after the switch to hypoxia, but it invariably reached its minimum value over the 3-min period following the switch back to air (Bollen et al, 2009). Although we termed this response HVD, we cannot discard that it involved after effects of hypoxia, i.e., post-hypoxic ventilatory decline (PHVD).…”

“…All quantifications were performed blind regarding the genotypes, which were determined after all tests were completed. Previous experiments in newborn mice (Bollen et al, 2009) indicated that the physiological responses to cold showed a large interindividual variability, which required a larger sample size in this condition.…”

“…Breathing variables were measured non-invasively using a battery of four whole-body flow barometric plethysmography, allowing the simultaneous measurement of breathing variables as previously described (Bollen et al, 2009). We used whole-body flow barometric plethysmography, rather than head-out plethysmography which provides a relatively direct measure of breathing, to avoid the stress related to restraint.…”

“…This coupling allows the fine-tuning of O 2 demand and supply, and enables the organism to cope with metabolic challenges (Mortola, 1999; Steiner and Branco, 2002; Chardon et al, 2004; Gargaglioni et al, 2005). In particular, newborns respond to oxygen demand by increasing ventilation, and then, if the demand persists, by decreasing the metabolic rate, thermogenesis and ventilation, an effect designated “hypoxic hypometabolism” (Frappell et al, 1992, 1998; Mortola, 1999, 2005; Bollen et al, 2009). The decrease in thermogenesis reflects a centrally regulated response rather than the mere limitation of oxygen availability (Mortola and Gautier, 1995; Gautier, 1996; Osaka, 2010).…”