Clusters of secretagogin-expressing neurons in the aged human olfactory tract lack terminal differentiation

Johannes Attems, Alan Alpar, Lauren Spence, Shane McParland, Mathias Heikenwalder, Mathias Uhlen, Heikki Tanila, Tomas G. M. Hokfelt*, Tibor Harkany

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

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 Ca2+ 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, beta-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.

Original languageEnglish
Pages (from-to)6259-6264
Number of pages6
JournalPNAS
Volume109
Issue number16
DOIs
Publication statusPublished - 17 Apr 2012

Keywords

  • binding
  • bulb
  • cells
  • calcium signaling
  • CA2+-binding protein
  • Alzheimers-Disease
  • subventricular zone
  • relay circuit
  • neuroblasts
  • neurogenesis
  • adult human brain
  • tau
  • migration
  • neurodegeneration
  • cat

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