Maintenance of taste receptor cell presynaptic sites requires gustatory nerve fibers.

The turnover and re-establishment of peripheral taste synapses is vital to maintain connectivity between the primary taste receptor cells and the gustatory neurons which relay taste information from the tongue to the brain. Despite the importance of neuron-taste cell reconnection, mechanisms governing synapse assembly and the specificity of synaptic connections is largely unknown. Here we use the expression of presynaptic proteins, CALHM1 and Bassoon, to probe whether nerve fiber connectivity is an initiating factor for the recruitment of presynaptic machinery in different populations of taste cells. Under homeostatic conditions, the vast majority (>90%) of presynaptic sites are directly adjacent to nerve fibers. In the days immediately following gustatory nerve transection and complete denervation, Bassoon and CALHM1 puncta are markedly reduced. This suggests that nerve fiber innervation is crucial for the recruitment and maintenance of presynaptic sites. In support of this, we find that expression of Bassoon and Calhm1 mRNA transcripts are significantly reduced after denervation. During nerve fiber regeneration into the taste bud, presynaptic sites begin to replenish, but are not as frequently connected to nerve fibers as intact controls (∼50% compared to >90%). This suggests that gustatory neuron proximity, rather than direct contact, likely drives taste receptor cells to express and aggregate presynaptic proteins at the cell membrane. Together, these data support the idea that trophic factors secreted by gustatory nerve fibers prompt taste receptor cells to produce presynaptic specializations at the cell membrane, which in turn may guide neurons to form mature synapses. These findings provide new insights into the mechanisms driving synaptogenesis and synaptic plasticity within the rapidly changing taste bud environment.

Give-and-take of gustation: the interplay between gustatory neurons and taste buds.

Mammalian taste buds are highly regenerative and can restore themselves after normal wear and tear of the lingual epithelium or following physical and chemical insults, including burns, chemotherapy, and nerve injury. This is due to the continual proliferation, differentiation, and maturation of taste progenitor cells, which then must reconnect with peripheral gustatory neurons to relay taste signals to the brain. The turnover and re-establishment of peripheral taste synapses are vital to maintain this complex sensory system. Over the past several decades, the signal transduction and neurotransmitter release mechanisms within taste cells have been well delineated. However, the complex dynamics between synaptic partners in the tongue (taste cell and gustatory neuron) are only partially understood. In this review, we highlight recent findings that have improved our understanding of the mechanisms governing connectivity and signaling within the taste bud and the still-unresolved questions regarding the complex interactions between taste cells and gustatory neurons.

Selective Peripheral Taste Dysfunction in APP/PS1 Mutant Transgenic Mice.

BACKGROUND: Previous studies indicate that taste dysfunction occurs early in the development of Alzheimer's disease. It is debatable whether the deficit in taste is due primarily to peripheral sensory mechanisms or to central processing, or a combination of the two. OBJECTIVE: The aim of our current study is to combine behavior and histological data in APP/PS1 transgenic mice to determine whether APP/PS1 transgenic mice show deficits in unconditioned taste preference and avoidance behaviors and whether taste impairments are due to defects in the peripheral taste system and/or problems with central processing of taste information. METHODS: The APP/PS1 transgenic mutant mice were used as a model of Alzheimer's disease. We employed a brief-access gustometer test to assess immediate orosensory taste responses of APP/PS1 mice. We used immunohistochemistry to examine tongue, gustatory ganglion, and brain tissues to determine a cytological basis for behavioral deficits. RESULTS: There is a significant, selective reduction of bitter taste sensitivity in APP/PS1 mice. These mice also have a loss of TRPM5-expressing taste receptor cells in the circumvallate papillae of the tongue. While we observed no overt loss of neuron cell bodies within the primary gustatory sensory neurons, degeneration of the neurons' peripheral axons innervating the taste bud may play a role in the observed loss of TRPM5-expressing taste receptor cells. CONCLUSION: This data supports a potential role for peripheral taste dysfunction in AD through the selective loss of taste receptor cells. Further study is necessary to delineate the mechanisms and pathological significance of this deficit in AD.