Taste bud-derived BDNF is required to maintain normal amounts of innervation to adult taste buds

Abstract

Gustatory neurons transmit chemical information from taste receptor cells, which reside in taste buds in the oral cavity, to the brain. As adult taste receptor cells are renewed at a constant rate, nerve fibers must reconnect with new taste receptor cells as they arise. Therefore, the maintenance of gustatory innervation to the taste bud is an active process. Understanding how this process is regulated is a fundamental concern of gustatory system biology. We speculated that because brain-derived neurotrophic factor (BDNF) is required for taste bud innervation during development, it might function to maintain innervation during adulthood. If so, taste buds should lose innervation when Bdnf is deleted in adult mice. To test this idea, we first removed Bdnf from all cells in adulthood using transgenic mice with inducible CreERT2 under the control of the Ubiquitin promoter. When Bdnf was removed, approximately half of the innervation to taste buds was lost, and taste buds became smaller due to the loss of taste bud cells. Individual taste buds varied in the amount of innervation each lost, and those that lost the most innervation also lost the most taste bud cells. We then tested the idea that that the taste bud was the source of this BDNF by reducing Bdnf levels specifically in the lingual epithelium and taste buds. Taste buds were confirmed as the source of BDNF regulating innervation. We conclude that BDNF expressed in taste receptor cells is required to maintain normal levels of innervation in adulthood.

Significance Statement: Numerous correlative studies have suggested that neurotrophins are required to maintain peripheral sensory innervation in adulthood. However, this has not been tested in any peripheral sensory system. Because the taste receptor cells undergo constant renewal, nerve fibers continually reconnect to new taste receptors cells, making the maintenance of innervation to the taste bud an active process. Therefore, if any sensory system requires neurotrophins for its maintenance, it is likely to be the taste system. We show here that taste bud derived BDNF is required to maintain normal amounts of innervation to the taste bud in adulthood. This demonstrates that neurotrophins maintain sensory innervation. The requirement for BDNF in taste buds may be important for the tremendous plasticity of this system.