Date on Master's Thesis/Doctoral Dissertation

8-2017

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Anatomical Sciences and Neurobiology

Degree Program

Anatomical Sciences and Neurobiology, PhD

Committee Chair

Krimm, Robin

Committee Co-Chair (if applicable)

Petruska, Jeffrey

Committee Member

Petruska, Jeffrey

Committee Member

Cai, Jun

Committee Member

Bickford, Martha

Committee Member

Lundy, Robert

Author's Keywords

BDNF; TrkB; taste bud; nerve fiber

Abstract

Taste receptor cells transduce stimuli transmitting information to gustatory neurons that carry it to the brain. They turn-over continuously in adulthood, and must be constantly reinnervated, making the maintenance of innervation to taste buds an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Taste bud innervation (40%) is lost when Bdnf is removed during adulthood, but it is unclear why remaining fibers were not lost. We found that some gustatory nerve fibers remained because they lack the TrkB receptor 55% of TrkB-labeled fibers were lost and fibers without TrkB remained following adult Bdnf gene recombination. It is unclear if BDNF has a direct function on the nerve fibers or could influence innervation indirectly by binding to taste bud cells, nor has it been determined which receptors mediate BDNF’s effects. BDNF functions through two receptors-TrkB and p75; furthermore TrkB has a truncated (TrkBT1) and full length form. Rt-PCR and immunohistochemistry determined that the full length TrkB receptor is expressed in the geniculate ganglion, but not in the taste buds, and both taste buds and the geniculate ganglion express TrkBT1 and p75. Furthermore, TrkBT1 was expressed in multiple types of taste bud cells. Finally, BDNF regu-lates TrkBT1 expression in the taste bud. We conclude that BDNF signaling via the full length TrkB receptor can only occur at nerve fibers, but BDNF could influence innervation indirectly via TrkBT1 or p75 expressed in taste receptors. Next we sought to determine whether BDNF functions through the full length TrkB receptor with a timing consistent with BDNF regulation of innervation during receptor cell turnover. A chemical genetic approach to block TrkB-signaling was combined with genetic labeling of subset of TrkB+ fibers to examine branching patterns in the taste bud. After blocking TrkB signaling for 2 weeks fewer taste buds are innervated by labeled TrkB-positive fibers and there was less labeled TrkB+ innervation in taste buds. Blocking TrkB signaling reduced the numbers of branches, and some higher order branches also become shorter. We conclude that BDNF functions through TrkB, encouraging fiber growth and branching with a timing consistent with TrkB-regulation of innervation to new taste receptor cells during renewal.

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