Thomas E. Finger

Persistent taste dysfunction is frequently reported in individuals with post-acute sequelae of infection by SARS-CoV-2 (long COVID). The mechanisms and pathological correlates underlying this taste dysfunction are unknown. This study investigates the underlying pathology in 28 non-hospitalized subjects diagnosed with COVID-19 who experienced taste disturbances more than 12 mo after testing positive for SARS-CoV-2. To objectively establish the nature of the taste deficit, we used the WETT taste test, which quantifies the subject's ability to taste each of the 5 taste qualities: sweet, umami, bitter, sour, and salty. We then biopsied 5 to 8 fungiform taste papillae (FP) in 20 of the 28 subjects. The FPs were analyzed histologically for overall taste bud (TB) structure and innervation and by quantitative PCR (qPCR) for mRNA expression of markers for different taste receptor cells. Although all subjects had reported taste dysfunction, only 3 showed overall taste scores below the 10th percentile for a normal population adjusted for age and sex. However, 11 of the 28 subjects exhibited total loss of one or more taste qualities. Loss of PLCβ2-dependent taste qualities (sweet, umami, and bitter) was significantly more common and was correlated with reduced expression of PLCβ2 and Tas1R3 mRNAs. Histological analysis revealed generally preserved TB structure and innervation but with occasional disorganized TBs and abnormal, isolated PLCβ2-positive cells in the epithelium. Our findings suggest long-term taste dysfunction after COVID-19 occurs rarely—more frequently involving PLCβ2-dependent taste qualities—but is not due to wholesale disruption of the taste periphery.

Persistent taste dysfunction is frequently reported in individuals with post-acute sequelae of infection by SARS-CoV-2 (Long COVID). The mechanisms and pathological correlates underlying this taste dysfunction are unknown. This study investigates the underlying pathology in 28 non-hospitalized subject's diagnosed with COVID-19 and who experienced taste disturbances more than 12 months after testing positive for SARS-CoV-2. To objectively establish the nature of taste deficit, we used the WETT taste test, which quantifies the subjects ability to taste each of the five taste qualities: sweet, umami, bitter, sour, and salty. We then biopsied five to eight fungiform taste papillae (FP) in 20 of the 28 subjects. The FPs were analyzed histologically for overall taste bud structure and innervation, and by quantitative PCR (qPCR) for mRNA expression of markers for different taste receptor cells. Although all subjects had reported taste dysfunction, only three showed overall taste scores below the 10th percentile for a normal population adjusted for age and sex. However, 11 of the 28 subjects exhibited total loss of one or more taste qualities. Loss of PLCβ2-dependent taste qualities (sweet, umami, bitter) was significantly more common and was correlated with reduced expression of PLCβ2 and Tas1R3 mRNAs. Histological analysis revealed generally preserved taste bud structure and innervation, but with occasional disorganized taste buds and abnormal, isolated PLCβ2-positive cells in the epithelium. Our findings suggest long-term taste dysfunction after COVID-19 occurs rarely -- more frequently involving PLCβ2-dependent taste qualities -- but is not due to wholesale disruption of the taste periphery.

Taste buds are commonly studied in rodent models, but some differences exist between mice and humans in terms of gustatory mechanisms and sensitivities. Whether these functional differences are reflected in structural differences between species is unclear. Using immunofluorescent image stacks, we compared the morphological and molecular characteristics of mouse and human fungiform taste buds. The results suggest that while the general features of fungiform taste buds are similar between mice and humans, several characteristics differ significantly. Human taste buds are larger and taller than those of mice, yet they contain similar numbers of taste cells. Taste buds in humans are more heavily innervated by gustatory nerve fibers expressing the purinergic receptor P2X3 showing a 40% higher innervation density than in mice. Like type II cells of mice, a subset (about 30%) of cells in human taste buds is immunoreactive for phospholipase C beta (PLCβ2). These PLCβ2-immunoreactive cells display calcium homeostasis modulator 1 (CALHM1)-immunoreactive puncta closely opposed to gustatory nerve fibers suggestive of channel-type synapses in type II cells in mice. These puncta, used as a measure of synaptic contact, are significantly larger in humans compared to mice suggesting a higher efflux of adenosine triphosphate (ATP) neurotransmitter in humans. Altogether these findings suggest that while many similarities exist in the organization of murine and human fungiform taste buds, significant differences do exist in taste bud size, innervation density, and size of synaptic contacts that may impact gustatory signal transmission.

Taste buds are commonly studied in rodent models, but some differences exist between mice and humans in terms of gustatory mechanisms and sensitivities. Whether these functional differences are reflected in structural differences between species is unclear. Using immunofluorescent image stacks, we compared morphological and molecular characteristics of mouse and human fungiform taste buds. The results suggest that while the general features of fungiform taste buds are similar between mice and humans, several characteristics differ significantly. Human taste buds are larger and taller than those of mice, yet they contain similar numbers of taste cells. Taste buds in humans are more heavily innervated by gustatory nerve fibers expressing the purinergic receptor P2X3 showing a 40% higher innervation density than in mice. Like Type II cells of mice, a subset (about 30%) of cells in human taste buds is immunoreactive for PLCβ2. These PLCβ2-immunoreactive cells display CALHM1-immunoreactive puncta closely apposed to gustatory nerve fibers suggestive of channel-type synapses described in mice. These puncta, used as a measure of synaptic contact, are however significantly larger in humans compared to mice. Altogether these findings suggest that while many similarities exist in the structural organization of murine and human fungiform taste buds, significant differences do exist in taste bud size, innervation density, and size of synaptic contacts that may impact gustatory signal transmission.

The cerebellum receives inputs via the climbing fibers originating from the inferior olivary nucleus in the ventral medulla. In mammals, the climbing fibers entwine and terminate onto both major and peripheral branches of dendrites of the Purkinje cells. In this study, the inferior olivary nucleus and climbing fiber in the goldfish were investigated with several histological techniques. By neural tracer application to the hemisphere of the cerebellum, labeled inferior olivary neurons were found in the ventral edge of the contralateral medulla. Kainate stimulated Co + + uptake and gephyrin immunoreactivities were found in inferior olivary neurons, indicating, respectively, that they receive both excitatory (glutamatergic) and inhibitory (GABAergic or glycinergic) inputs. Inferior olivary neurons express vglut2.1 transcripts, suggesting they are glutamatergic. Around 85% of inferior olivary neurons were labeled with anti-calretinin antiserum. Calretinin immunoreactive (ir) climbing fiber terminal-like structures were distributed near the Purkinje cells and in the molecular layer. Double labeling immunofluorescence with anti-calretinin and zebrin II antisera revealed that the calretinin-ir climbing fibers run along and made synaptic-like contacts on the major dendrites of the zebrin II-ir Purkinje cells. In teleost fish, cerebellar efferent neurons, eurydendroid cells, also lie near the Purkinje cells and extend dendrites outward to intermingle with dendrites of the Purkinje cells within the molecular layer. Here we found no contacts between the climbing fiber terminals and the eurydendroid cell dendrites. These results support the idea that Purkinje cells, but not eurydendroid cells, receive strong inputs via the climbing fibers, similar to the mammalian situation.

Puppies chew on everything -- from rugs to furniture to shoes. Most people try to discourage this activity and for deterrence, utilize various commercial products, which include bitter tastants such as denatonium benzoate. Although denatonium is remarkably bitter to people (at about 20μM), it is less so for other mammals, including mice (about 100μM). The current study by Gibbs and coworkers tests the potency of various bitter substances, including denatonium, in dog taste preference tests as well as in the activation of heterologously expressed dog bitter receptors. Humans have about 25 bitter receptors {1}, while dogs have but 16. Many of the more denatonium-sensitive receptors present in humans are lacking in dogs leaving dogs with a denatonium sensitivity similar to mice. This means that many commercial products that utilize denatonium as a feeding deterrent will be only marginally effective for dogs. The supplementary data shown in Fig S2 of this paper is quite interesting showing the response spectrum of nearly half of the dog bitter receptors.

Taste buds comprise 50-100 specialized epithelial cells, about half of which serve a direct function in taste transduction and synapse onto the afferent nerve fibers. The Type II cells which mediate sweet, umami, and bitter transduction utilize a unique type of synapse, a so-called channel synapse, which relies on gated large pore channels to release ATP, the key neurotransmitter in this system {1,2}. The channel synapse protein, CALHM1 serves as a useful marker for these sites of synaptic contact. The other transducing cells of the taste bud, Type III cells, respond to acids (sour) and rely on conventional vesicle-type synapses {3}. The current work reveals that the pre-synaptic protein Basson serves as a means for identifying the synaptic loci from the Type III cells. This added marker, along with CALHM1, then allows for a complete characterization of synaptic sites in taste buds without requiring extensive serial section electron microscopy {4}.

This article utilizes a novel approach to establishing the presence of contacts between neural processes as are necessary for synaptic interaction. Essentially, the method relies on the limits of optical resolution to identify points of contact. If two processes do make contact, then even with at the limits of optical resolution, there should be a line of pixels showing colocalization, although the two objects cannot physically occupy the same point in space. If unlabeled pixels exist between two objects, then they cannot be in synaptic contact. The authors utilize this clever method to show convergence of input from gustatory nerves innervating different oral structures onto single post-synaptic cells, but this method can be applied generally to microanalysis of circuity in any neural system.

Loss of taste and smell have been recognized as key indicators of SARS-CoV-2 infection {1}. Popular reports of loss of taste are, however, confounded by the general confusion of taste and flavor -- taste, as mediated by taste buds, is limited to the qualities of salt, sweet, sour, bitter, and umami, whereas flavor is a combined perception of taste and retronasal olfaction. The biological basis for loss of olfaction is relatively clear and involves primary infection of the supporting cells of the mucosa which express the ACE2 receptor and the resulting inflammation-causing loss of function of the olfactory sensory neurons {2}. Nonetheless, taste loss is also well documented {3}. This paper by Doyle and co-workers offers a biological basis for the loss of taste function. The ACE2 receptors can be detected in a subpopulation of taste receptor cells (Type II cells) which showed the presence of the virus in an infected patient. Further, the authors present evidence for post-infection disruption of the natural turn-over of taste cells perhaps accounting for the slow recovery of full function in some patients.