Abstract
Is the cerebrum involved in its own activation to states of attention or arousal? “Telencephalon” is a term borrowed from embryology to identify not only the cerebral hemispheres of the forebrain, but also the basal forebrain. We review a generally undercited literature that describes nucleus basalis of Meynert, located within the substantia innominata of the ventrobasal forebrain, as a telencephalic extension of the ascending reticular activating formation. Although that formation’s precise anatomical definition and localization have proven elusive over more than 70 years, a careful reading of sources reveals that there are histological features common to certain brainstem neurons and those of the nucleus basalis, and that a largely common dendritic architecture may be a morphological aspect that helps to define non-telencephalic structures of the ascending reticular activating formation (e.g., in brainstem) as well as those parts of the formation that are telencephalic and themselves responsible for cortical activation. We draw attention to a pattern of dendritic arborization described as “isodendritic,” a uniform (isos-) branching in which distal dendrite branches are significantly longer than proximal ones. Isodendritic neurons also differ from other morphological types based on their heterogeneous, rather than specific afferentation. References reviewed here are consistent in their descriptions of histology, particularly in studies of locales rich in cholinergic neurons. We discuss the therapeutic implications of a basal forebrain site that may activate cortex. Interventions that specifically target nucleus basalis and, especially, the survival of its constituent neurons may benefit afflictions in which higher cortical function is compromised due to disturbed arousal or attentiveness, including not only coma and related syndromes, but also conditions colloquially described as states of cognitive “fog” or of “long-haul” mental compromise.
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Acknowledgements
Umberto DeGirolami, M.D. (Mass General Brigham Department of Pathology and Harvard Medical School) helped with the translation of Mannen (1960); he corroborated, corrected, and then elaborated on the first author’s translation. The authors thank Drs. Vikram Khurana and Tracy Young-Pearse, both from Mass General Brigham Department of Neurology and Harvard Medical School, for discussions relevant to the uses of induced pluripotent stem cells.
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E.K.M. reports no funding sources. S.B. receives support from the Judy Pauline Staples Aull Fund at Brigham and Women’s Hospital, Boston, MA USA and research support from Alexion Pharmaceuticals and National Institute of Health under award number OT2HL161847-01. M.T. is supported by the National Cancer Institute of the National Institutes of Health under award number F32CA257210. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Miyawaki, E.K., Bhattacharyya, S. & Torre, M. Revisiting a Telencephalic Extent of the Ascending Reticular Activating System. Cell Mol Neurobiol 43, 2591–2602 (2023). https://doi.org/10.1007/s10571-023-01339-3
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DOI: https://doi.org/10.1007/s10571-023-01339-3