Deletion of voltage-gated channel affects glomerular refinement and odorant receptor expression in the mouse olfactory system

K. C. Biju, David Ronald Marks, Thomas Gerald Mast, Debra Ann Fadool

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Olfactory sensory neurons (OSNs) expressing a specific odorant receptor (OR) gene send axonal projections to specific glomeruli, creating a stereotypic olfactory sensory map. Odorant receptor sequence, G-protein cAMP signaling, and axon guidance molecules have been shown to direct axons of OSNs toward central targets in the olfactory bulb (OB). Although the OR sequence may act as one determinant, our objective was to elucidate the extent by which voltage-dependent activity of postsynaptic projection neurons in the OB centrally influences peripheral development and target destination of OSNs. We bred OR-tagged transgenic mice to homozygosity with mice that had a gene-targeted deletion of the Shaker potassium ion channel (Kv1.3) to elucidate how activity modulates synaptic connections that formulate the sensory map. Here we report that the Kv1.3 ion channel, which is predominantly expressed in mitral cells and whose gene-targeted deletion causes a "super-smeller" phenotype, alters synaptic refinement of axonal projections from OSNs expressing P2, M72, and MOR28 ORs. Absence of Kv1.3 voltage-gated activity caused the formation of small, heterogeneous, and supernumerary glomeruli that failed to undergo neural pruning over development. These changes were accompanied by a significant decrease in the number of P2-, M72-, and MOR28-expressing OSNs, which contained an overexpression of OR protein and G-protein Golf in the cilia of the olfactory epithelium. These findings suggest that voltage-gated activity of projection neurons is essential to refine primary olfactory projections and that it regulates proper expression of the transduction machinery at the periphery.

Original languageEnglish (US)
Pages (from-to)161-179
Number of pages19
JournalJournal of Comparative Neurology
Volume506
Issue number2
DOIs
StatePublished - Jan 10 2008
Externally publishedYes

Keywords

  • Axon targeting
  • Kv1.3
  • Odorant receptor
  • Olfaction
  • Olfactory coding

ASJC Scopus subject areas

  • Neuroscience(all)

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