The recent discovery of a barbiturate-sensitive "general anesthesia switch" mechanism localized in the rat brain stem mesopontine tegmental anesthesia area (MPTA) has challenged the current view of the nonspecific actions of general anesthetic agents in the CNS. In this study we provide electrophysiological evidence that the antinociception, which accompanies the behavioral state resembling general anesthesia following pentobarbital (PB) microinjections into the MPTA of awake rats, could be accompanied by the attenuation of sensory transmission through the spinothalamic tract (STT). Following bilateral microinjections of PB into the MPTA spontaneous firing rate (SFR), antidromic firing index (FI), and sciatic (Sc) as well as sural (Su) nerve-evoked responses (ER) of identified lumbar STT neurons in the isoflurane-anesthetized rat were quantified using extracellular recording techniques. Microinjections of PB into the MPTA significantly suppressed the SFR (47%), magnitudes of Sc- (26%) and Su-ER (36%), and FI (41%) of STT neurons. Microinjections of PB-free vehicle control did not alter any of the above-cited electrophysiological parameters. The results from this study suggest that antinociception, which occurs during the anesthesia-like state following PB microinjections into the MPTA, may be due, in part, to (in)direct inhibition of STT neurons via switching mechanism(s) located in the MPTA. This study provides a provenance for investigating electrophysiologically the actions on STT neurons of other current agents used clinically to maintain the state of general anesthesia.
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http://dx.doi.org/10.1152/jn.90933.2008 | DOI Listing |
Front Mol Neurosci
May 2023
Department of Cell and Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
The canonical view of how general anesthetics induce loss-of-consciousness (LOC) permitting pain-free surgery posits that anesthetic molecules, distributed throughout the CNS, suppress neural activity globally to levels at which the cerebral cortex can no longer sustain conscious experience. We support an alternative view that LOC, in the context of GABAergic anesthesia at least, results from anesthetic exposure of a small number of neurons in a focal brainstem nucleus, the mesopontine tegmental anesthesia area (MPTA). The various sub-components of anesthesia, in turn, are effected in distant locations, driven by dedicated axonal pathways.
View Article and Find Full Text PDFExp Neurol
November 2022
Department of Cell and Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem; Jerusalem 9190401, Israel; Center for Research on Pain, The Hebrew University of Jerusalem; Jerusalem 9190401, Israel.
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.
View Article and Find Full Text PDFExp Brain Res
November 2021
Department of Cell and Developmental Biology, Silberman Institute of Life Sciences 3-533, The Hebrew University of Jerusalem, 9190401, Jerusalem, Israel.
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 similar results in mice has been challenging, however, slowing research progress on how anesthetics trigger brain-state transitions. We have identified roadblocks that impeded translation from rat to mouse and tentatively located the MPTA equivalent in this second species.
View Article and Find Full Text PDFExp Neurol
September 2021
Department of Cell and Developmental Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel; Center for Research on Pain, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. Electronic address:
General anesthetic agents are thought to induce loss-of-consciousness (LOC) and enable pain-free surgery by acting on the endogenous brain circuitry responsible for sleep-wake cycling. In clinical use, the entire CNS is exposed to anesthetic molecules with LOC and amnesia usually attributed to synaptic suppression in the cerebral cortex and immobility and analgesia to agent action in the spinal cord and brainstem. This model of patch-wise suppression has been challenged, however, by the observation that all functional components of anesthesia can be induced by focal delivery of minute quantities of GABAergic agonists to the brainstem mesopontine tegmental anesthesia area (MPTA).
View Article and Find Full Text PDFNeuroscience
April 2020
Department of Cell and Developmental Biology, Silberman Institute of Life Sciences, Jerusalem 9190401, Israel; The Center for Research on Pain, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel. Electronic address:
The mesopontine tegmental anesthesia area (MPTA) is a small brainstem nucleus that, when exposed to minute quantities of GABA receptor agonists, induces a state of general anesthesia. In addition to immobility and analgesia this state is accompanied by widespread suppression of neural activity in the cerebral cortex and high delta-band power in the electroencephalogram. Collectively, MPTA neurons are known to project to a variety of forebrain targets which are known to relay to the cortex in a highly distributed manner.
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