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Genetic lineage tracing shows the remarkable heterogeneity of brainstem noradrenergic neurons, which may explain their varied functions. They project to the locus coeruleus, the primary source of noradrenaline in the brain, which supports learning and cognition. They also project to pre\u2010ganglionic neurons, which lie within the spinal cord and form synapses onto post\u2010ganglionic neurons. The synapse between descending brainstem noradrenergic neurons and pre\u2010ganglionic spinal neurons, and these in turn with post\u2010ganglionic noradrenergic neurons located at the paravertebral sympathetic ganglia, support an anatomical hierarchy that regulates skeletal muscle innervation, neuromuscular transmission, and muscle trophism. Whether any noradrenergic neuron subpopulation is more susceptible to damaged protein deposit and death with ageing and neurodegeneration is a relevant question that answer will help us to detect neurodegeneration at an early stage, establish prognosis, and anticipate disease progression. Loss of muscle mass and strength with ageing, termed<jats:italic>sarcopenia<\/jats:italic>, may predict impaired cognition with ageing and neurodegeneration and establish an early time to start interventions aimed at reducing central noradrenergic neurons hyperactivity. Complex multidisciplinary approaches, including genetic tracing, specific circuit labelling, optogenetics and chemogenetics, electrophysiology, and single\u2010cell transcriptomics and proteomics, are required to test this hypothesis pre\u2010clinical.<\/jats:p>","DOI":"10.1111\/apha.13887","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T06:50:27Z","timestamp":1662619827000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Brainstem noradrenergic neurons: Identifying a hub at the intersection of cognition, motility, and skeletal muscle regulation"],"prefix":"10.1111","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1613-8202","authenticated-orcid":false,"given":"Osvaldo","family":"Delbono","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Section on Gerontology and Geriatric Medicine. 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