Figure - available from: Experimental Brain Research
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Continuous isoflurane flow protocol. “On-target” trials of muscimol microinjection into the mesopontine tegmentum are those which extended anesthesia time beyond that attributable to residual circulating isoflurane (ISO). These define the location of the MPTA. Symbols indicate results of individual trials in the mouse indicated. A Time to emergence from anesthesia after stopping the flow of isoflurane, marked by the onset of rhythmic limb pacing movements, averaged 5.0 min (solid horizontal line) ± 3.5 min (± SD, dashed horizontal lines) in 12 DBA/2 strain mice (all males). B Like A but in trials in which muscimol was microinjected into the mesopontine tegmentum at the time isoflurane flow was stopped. Subtracting the average time attributable to residual isoflurane from A (solid horizontal line marked with a red arrow) yields the bonus time attributable to the muscimol. Those trials in which bonus time exceeded the mean baseline isoflurane anesthesia time by 3 × SD were considered statistically significant. Only 2 trials, in mouse #6 and #7, met this criterion. C Same as A., but results from 10 B6 mice, all females except for #13, 14, 22. D Same as B. B6 mice. 6 trials in 5 mice reached statistical significance
The mesopontine tegmental anesthesia area (MPTA) was identified in rats as a singular brainstem locus at which microinjection of minute quantities of GABAergic agents rapidly and reversibly induces loss-of-consciousness and a state of general anesthesia, while lesioning renders animals insensitive to anesthetics at normal systemic doses. Obtaining...
Although general anesthesia is normally induced by systemic dosing, an anesthetic state can be induced in rodents by microinjecting minute quantities of GABAergic agents into the brainstem mesopontine tegmental anesthesia area (MPTA). Correspondingly, lesions to the MPTA render rats relatively insensitive to standard anesthetic doses delivered systemically. Using a chemogenetic approach we have identified and characterized a small subpopulation of neurons restricted to the MPTA which, when excited, render the animal anesthetic by sensorimotor (immobility) and electroencephalographic (EEG) criteria. These “effector-neurons” do not express GABAAδ-Rs, the likely target of GABAergic anesthetics. Rather, we report a distinct sub-population of nearby MPTA neurons which do. During anesthetic induction these likely excite the effector-neurons by disinhibition. Within the effector population ~ 70% appear to be glutamatergic, ~30% GABAergic and ~ 40% glycinergic. Most are projection neurons that send ascending or descending axons to distant targets associated with the individual functional components of general anesthesia: atonia, analgesia, amnesia, and loss-of-consciousness.