title: Clusters of secretagogin-expressing neurons in the aged human olfactory tract lack terminal differentiation.
abstract: Expanding the repertoire of molecularly diverse neurons in the human nervous system is paramount to characterizing the neuronal networks that underpin sensory processing. Defining neuronal identities is particularly timely in the human olfactory system, whose structural differences from nonprimate macrosmatic species have recently gained momentum. Here, we identify clusters of bipolar neurons in a previously unknown outer "shell" domain of the human olfactory tract, which express secretagogin, a cytosolic Ca(2+) binding protein. These "shell" neurons are wired into the olfactory circuitry because they can receive mixed synaptic inputs. Unexpectedly, secretagogin is often coexpressed with polysialylated-neural cell adhesion molecule, β-III-tubulin, and calretinin, suggesting that these neurons represent a cell pool that might have escaped terminal differentiation into the olfactory circuitry. We hypothesized that secretagogin-containing "shell" cells may be eliminated from the olfactory axis under neurodegenerative conditions. Indeed, the density, but not the morphological or neurochemical integrity, of secretagogin-positive neurons selectively decreases in the olfactory tract in Alzheimer's disease. In conclusion, secretagogin identifies a previously undescribed cell pool whose cytoarchitectonic arrangements and synaptic connectivity are poised to modulate olfactory processing in humans.
authors.affiliation: Institute for Ageing and Health,  Newcastle University, Newcastle upon Tyne NE4 5PL,  United Kingdom.
authors.forename: Johannes
authors.initials: J
authors.lastname: Attems
authors.forename: Alan
authors.initials: A
authors.lastname: Alpar
authors.forename: Lauren
authors.initials: L
authors.lastname: Spence
authors.forename: Shane
authors.initials: S
authors.lastname: McParland
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.forename: Heikki
authors.initials: H
authors.lastname: Tanila
authors.forename: Tomas G M
authors.initials: TG
authors.lastname: Hökfelt
authors.forename: Tibor
authors.initials: T
authors.lastname: Harkany
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001344:Autopsy; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D002452:Cell Count; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism; D009833:Olfactory Pathways / Q000166:cytology / Q000378:metabolism*; D064046:Secretagogins; D016708:Synaptophysin / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; C576556:SCGN protein, human; D064046:Secretagogins; D016708:Synaptophysin; C494807:VAMP2 protein, human; D050988:Vesicle-Associated Membrane Protein 2