Individual Mesopontine Neurons Implicated in Anesthetic Loss-of-consciousness Employ Separate Ascending Pathways to the Cerebral Cortex. (15th April 2020)

• Record Type: Journal Article
• Authors: Lellouche, Yair; Minert, Anne; Schreiber, Caterin; Aroch, Ilil; Vaso, Kristina; Fishman, Yelena; Devor, Marshall
• Is Part Of: Neuroscience. Volume 432(2020)
• Page Start: 188
• Page End: 204
• Publication Date: 2020-04-15
• Subjects: anesthesia -- basal forebrain -- collateralization -- MPTA -- thalamo-cortical -- zona incerta; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.02.022
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Exposure of MPTA neurons to GABAergic agonists induces anesthesia by recruiting dedicated axonal pathways. Ascending projections to basal forebrain, zona incerta and intralaminar thalamus likely relay MPTA signals to the cortex. Double-retrograde tracing revealed that individual MPTA neurons project to only one of these three relays. Ascending axons project ipsilaterally or contralaterally, with a 2:1 ipsilateral preference, but not bilaterally. This collateralization architecture may enable regional control of EEG patterning, permitting local and unihemispheric sleep. Abstract: The mesopontine tegmental anesthesia area (MPTA) is a small brainstem nucleus that, when exposed to minute quantities of GABAA 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. Here we ask whether ascending projections of individual MPTA neurons collateralize to several of these cortical relay nuclei, or access only one. Using rats, contrasting retrograde tracers were microinjected pairwise on one side into three ascending relays: the basal forebrain, the zona incerta-lateral hypothalamus and the intralaminar thalamic nuclear group. In addition, in separate animals, each target was microinjected bilaterally. MPTA neurons were then identified as being single-or double-labeled, indicating projection to one target nucleus or collateralization to both. Results indicated that double-labeling was rare, occurring on average in only 1.3% of the neurons sampled. The overwhelming majority of individual MPTA neurons showed specific connectivity, contributing to only one of the major ascending pathways, either ipsilaterally or contralaterally, but not bilaterally. This architecture would permit particular functional aspects of anesthetic loss-of-consciousness to be driven by specific subpopulations of MPTA neurons.