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Peripheral taste receptor cells use multiple signaling pathways to transduce taste stimuli into output signals that are sent to the brain. We have previously identified a subpopulation of Type III taste cells that are broadly responsive (BR) and respond to multiple taste stimuli including bitter, sweet, umami, and sour. These BR cells use a PLCβ3/IP₃R1 signaling pathway to detect bitter, sweet, and umami stimuli and use a separate pathway to detect sour. Currently, the downstream targets of the PLCβ3 signaling pathway are unknown. Here we identify TRPM4, a monovalent selective TRP channel, as an important downstream component in this signaling pathway. Using live cell imaging on isolated taste receptor cells from mice, we show that inhibition of TRPM4 abolished the taste-evoked sodium responses and significantly reduced the taste-evoked calcium responses in BR cells. Since BR cells are a subpopulation of Type III taste cells, they have conventional chemical synapses that require the activation of voltage-gated calcium channels (VGCCs) to cause neurotransmitter release. We found that TRPM4-dependent membrane depolarization selectively activates L-type VGCCs in these cells. The calcium influx through L-type VGCCs also generates a calcium-induced calcium release (CICR) via ryanodine receptors that enhances TRPM4 activity. Together these signaling events amplify the initial taste response to generate an appropriate output signal. 

Abstract In April 2023, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in partnership with the National Institute of Child Health and Human Development, the National Institute on Aging, and the Office of Behavioral and Social Sciences Research, hosted a 2‐day online workshop to discuss neural plasticity in energy homeostasis and obesity. The goal was to provide a broad view of current knowledge while identifying research questions and challenges regarding neural systems that control food intake and energy balance. This review includes highlights from the meeting and is intended both to introduce unfamiliar audiences with concepts central to energy homeostasis, feeding, and obesity and to highlight up‐and‐coming research in these areas that may be of special interest to those with a background in these fields. The overarching theme of this review addresses plasticity within the central and peripheral nervous systems that regulates and influences eating, emphasizing distinctions between healthy and disease states. This is by no means a comprehensive review because this is a broad and rapidly developing area. However, we have pointed out relevant reviews and primary articles throughout, as well as gaps in current understanding and opportunities for developments in the field.