title: Von Economo Neurons and Fork Cells: A Neurochemical Signature Linked to Monoaminergic Function.
abstract: The human anterior cingulate and frontoinsular cortices are distinguished by 2 unique Layer 5 neuronal morphotypes, the von Economo neurons (VENs) and fork cells, whose biological identity remains mysterious. Insights could impact research on diverse neuropsychiatric diseases to which these cells have been linked. Here, we leveraged the Allen Brain Atlas to evaluate mRNA expression of 176 neurotransmitter-related genes and identified vesicular monoamine transporter 2 (VMAT2), gamma-aminobutyric acid (GABA) receptor subunit θ (GABRQ), and adrenoreceptor α-1A (ADRA1A) expression in human VENs, fork cells, and a minority of neighboring Layer 5 neurons. We confirmed these results using immunohistochemistry or in situ hybridization. VMAT2 and GABRQ expression was absent in mouse cerebral cortex. Although VMAT2 is known to package monoamines into synaptic vesicles, in VENs and fork cells its expression occurs in the absence of monoamine-synthesizing enzymes or reuptake transporters. Thus, VENs and fork cells may possess a novel, uncharacterized mode of cortical monoaminergic function that distinguishes them from most other mammalian Layer 5 neurons.
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Anke A
authors.initials: AA
authors.lastname: Dijkstra
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Lin
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Alissa L
authors.initials: AL
authors.lastname: Nana
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Gaus
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California, San Francisco.|Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001271:Atlases as Topic; D015306:Biogenic Monoamines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D002648:Child; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008253:Macaca mulatta; D051379:Mice; D008875:Middle Aged; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D013045:Species Specificity; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: C547713:ADRA1A protein, human; D015306:Biogenic Monoamines; C561870:GABRQ protein, human; D050480:Plasma Membrane Neurotransmitter Transport Proteins; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D011963:Receptors, GABA-A; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins
keywords: ADRA1A; GABRQ; VMAT2; fork cells; von Economo neurons