Mesopontine tegmental anesthesia area projects independently to the rostromedial medulla and to the spinal cord.

General anesthetics are presumed to act in a distributed manner throughout the CNS. However, we found that microinjection of GABAA-receptor (GABAA-R) active anesthetics into a restricted locus in the rat brainstem, the mesopontine tegmental anesthesia area (MPTA), rapidly induces a reversible anesthesia-like state characterized by suppressed locomotion, atonia, anti-nociception and loss of consciousness. GABA-sensitive neurons in the MPTA may therefore have powerful control over major aspects of brain and spinal function. Tracer studies have shown that the MPTA projects to the rostromedial medulla, an important reticulospinal relay for pain modulation and motor control. It also projects directly to the spinal cord. But do individual MPTA neurons project to one or to both targets? We microinjected fluorogold into the rostromedial medulla and cholera toxin b-subunit into the spinal cord, or vice versa. Neurons that were double-labeled, and hence project to both targets, were intermingled with single-labeled neurons within the MPTA, and comprised only 11.5% of the total. MPTA neurons that project directly to the spinal cord were larger, on average, than those projecting to the rostromedial medulla, differed in shape, and were much more likely to express GABAA-alpha1Rs as assessed by receptor alpha-1 subunit immunoreactivity (51.4% vs. 18.9%). Thus, for the most part, separate and morphologically distinct populations of MPTA neurons project to the rostromedial medulla and to the spinal cord. Either or both may be involved in the modulation of nociception and the generation of atonia during the MPTA-induced anesthesia-like state.