Enhanced wakefulness following lesions of a mesopontine locus essential for the induction of general anesthesia.

The induction of general anesthesia shares many features with the transition from wakefulness to non-rapid eye movement (NREM) sleep, suggesting that the two types of brain-state transition are orchestrated by a common neuronal mechanism. Previous studies revealed a brainstem locus, the mesopontine tegmental anesthesia area (MPTA), that is of singular importance for anesthetic induction. Microinjection of GABAergic anesthetics there induces rapid loss-of-consciousness and lesions render the animal relatively insensitive to anesthetics administered systemically. Here we show that MPTA lesions also alter the natural sleep-wake rhythm by increasing overall wake time at the expense of time asleep (NREM and REM sleep equally), with nearly all of the change occurring during the dark hours of the light-dark cycle. The effect was proportional to the extent of the lesion and was not seen after lesions just outside of the MPTA, or following sham lesions. Thus, MPTA neurons appear to play a role in natural bistable brain-state switching (sleep-wake) as well as in loss and recovery of consciousness induced pharmacologically.

Transient loss of consciousness during hypercapnia and hypoxia: Involvement of pathways associated with general anesthesia.

Transient loss of consciousness (TLOC), frequently triggered by perturbation in essential physiological parameters such as pCO2 or O2, is considered a passive consequence of generalized degradation in high-level cerebral functioning. However, the fact that it is almost always accompanied by atonia and loss of spinal nocifensive reflexes suggests that it might actually be part of a "syndrome" mediated by neural circuitry, and ultimately be adaptive. Widespread suppression by molecules distributed in the vasculature is also the classical explanation of general anesthesia. Recent data, however, suggest that anesthesia is due, rather, to drug action at a specific brainstem locus, the mesopontine tegmental anesthesia area (MPTA), with the spectrum of anesthetic effects resulting from secondary recruitment of specific axonal pathways. If so, might the MPTA also be involved in TLOC induced by hypercapnia and hypoxia? We exposed rats to gas mixtures that provoke hypercapnia and hypoxia and asked whether cell-selective lesions of the MPTA affect TLOC. Entry into TLOC, monitored as time to loss of the righting reflex (LORR) was unaffected. However, resumption of the righting reflex (RORR), and of response to pinch stimuli (ROPR), was significantly delayed. The extent of both effects correlated with the extent of damage in the MPTA, but was unrelated to damage that extended beyond the borders of the MPTA. The results implicate neurons in a specific common-core region of the MPTA in TLOC induced by both forms of asphyxia. This is the same area responsible for general anesthesia induced by GABAergic anesthetic agents. This implies the involvement of a common set of brain nuclei and dedicated axonal pathways, rather than nonspecific global suppression, in the mechanism mediating all three instances of TLOC.