Scientific Understanding of Consciousness
Taste System Fidelity of Signaling
Nature 548, 330–333 (17 August 2017)
Rewiring the taste system
Hojoon Lee, et.al.
Howard Hughes Medical Institute, Department of Neuroscience, Columbia College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
In mammals, taste buds typically contain 50–100 tightly packed taste-receptor cells (TRCs), representing all five basic qualities: sweet, sour, bitter, salty and umaml. Notably, mature taste cells have life spans of only 5–20 days and, consequently, are constantly replenished by differentiation of taste stem cells. Given the importance of establishing and maintaining appropriate connectivity between TRCs and their partner ganglion neurons (that is, ensuring that a labelled line from sweet TRCs connects to sweet neurons, bitter TRCs to bitter neurons, sour to sour, and so on), we examined how new connections are specified to retain fidelity of signal transmission. Here we show that bitter and sweet TRCs provide instructive signals to bitter and sweet target neurons via different guidance molecules (SEMA3A and SEMA7A). We demonstrate that targeted expression of SEMA3A or SEMA7A in different classes of TRCs produces peripheral taste systems with miswired sweet or bitter cells. Indeed, we engineered mice with bitter neurons that now responded to sweet tastants, sweet neurons that responded to bitter or sweet neurons responding to sour stimuli. Together, these results uncover the basic logic of the wiring of the taste system at the periphery, and illustrate how a labelled-line sensory circuit preserves signalling integrity despite rapid and stochastic turnover of receptor cells.
Unlike the wiring of the mammalian olfactory system, where odorant receptors have a key role in directing connectivity between olfactory neurons and their targets in the olfactory bulb, taste receptors themselves are not essential for establishing connectivity between TRCs and their targets (that is, TRCs lacking taste receptors still signal properly when expressing engineered receptors). Thus, we reasoned that as new TRCs are produced, they must express dedicated molecular cues that act as permissive and/or instructive signals to establish connectivity with the right complement of taste neurons.
The taste system affords the unique opportunity to explore how labelled lines between primary sensory cells and neurons are wired and preserved. At the periphery, five basic classes of TRCs signal to a matching set of ganglion neurons. But how ganglion processes identify their proper TRC partners has remained unclear. The chemoaffinity hypothesis has been a tenet of neuronal connectivity for over 100 years. Yet, despite much effort, there are limited examples in vertebrates where guidance molecules expressed by target cells direct cell to cell connectivity, rather than ‘regional’ level connectivity. Because taste cells are assembled into tightly packed taste buds (with a random distribution of TRCs that represent each modality), they provide an ideal experimental platform to explore how connectivity rules may operate at a cell-to-cell level. Moreover, as TRCs are constantly renewed during the life of the animal, they require continuous re-establishment of connections between existing ganglion processes and newly born TRCs. Here, we combine single-cell functional imaging and mouse genetics to demonstrate that sweet and bitter TRCs use distinct semaphorins in a deterministic fashion to guide wiring of the peripheral taste system (probably together with other connectivity molecules as part of a multi-component wiring specificity code). Our results show how targeted misexpression of even a single connectivity signal alters taste cell–neuronal communication in a predictable fashion (for example, sweet signalling to bitter, or sour to sweet). Together, these studies reveal basic rules of TRC–neuron connectivity, substantiate the labelled-line organization of the taste system, and help to explain how a hardwired sensory system maintains fidelity of signalling in the face of random turnover of receptor cells.
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