Transient receptor potential (TRP) channels and taste sensation.
ABSTRACT Humans have 5 basic taste sensations: sweet, bitter, sour, salty, and umami (taste of 1-amino acids). Among 33 genes related to transient receptor potential (TRP) channels, 3--including TRP-melastatin 5 (TRPM5), polycystic kidney disease-1-like 3 (PKD1L3), and polycystic kidney disease-2-like 1 (PKD2L1)--are specifically and abundantly expressed in taste receptor cells. TRP-melastatin 5 is co-expressed with taste receptors T1Rs and T2Rs, and functions as a common downstream component in sweet, bitter, and umami taste signal transduction. In contrast, polycystic kidney disease-1-like 3 and polycystic kidney disease-2-like 1 are co-expressed in distinct subsets of taste receptor cells not expressing TRP-melastatin 5. In the heterologous expression system, cells expressing both polycystic kidney disease-1-like 3 and polycystic kidney disease-2-like 1 responded to sour stimuli, showing a unique "off-response" property. Genetic ablation of poly-cystic kidney disease-2-like 1-expressing cells resulted in elimination of gustatory nerve response to sour stimuli, indicating that cells expressing polycystic kidney disease-2-like 1 function as sour taste detectors. These results suggest that polycystic kidney disease-1-like 3/polycystic kidney disease-2-like 1 may play a significant role, possibly as taste receptors, in sour taste sensation.
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ABSTRACT: Triggered by recent experimental results, temporally asymmetric Hebbian (TAH) plasticity is considered as a candidate model for the biological implementation of competitive synaptic learning, a key concept for the experience-based development of cortical circuitry. However, because of the well known positive feedback instability of correlation-based plasticity, the stability of the resulting learning process has remained a central problem. Plagued by either a runaway of the synaptic efficacies or a greatly reduced sensitivity to input correlations, the learning performance of current models is limited. Here we introduce a novel generalized nonlinear TAH learning rule that allows a balance between stability and sensitivity of learning. Using this rule, we study the capacity of the system to learn patterns of correlations between afferent spike trains. Specifically, we address the question of under which conditions learning induces spontaneous symmetry breaking and leads to inhomogeneous synaptic distributions that capture the structure of the input correlations. To study the efficiency of learning temporal relationships between afferent spike trains through TAH plasticity, we introduce a novel sensitivity measure that quantifies the amount of information about the correlation structure in the input, a learning rule capable of storing in the synaptic weights. We demonstrate that by adjusting the weight dependence of the synaptic changes in TAH plasticity, it is possible to enhance the synaptic representation of temporal input correlations while maintaining the system in a stable learning regime. Indeed, for a given distribution of inputs, the learning efficiency can be optimized.Journal of Neuroscience 06/2003; 23(9):3697-714. · 7.11 Impact Factor
Article: Double-chambered right ventricle.European Heart Journal 10/2007; 28(18):2237. · 10.48 Impact Factor
Article: Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5.[show abstract] [hide abstract]
ABSTRACT: The transduction of taste is a fundamental process that allows animals to discriminate nutritious from noxious substances. Three taste modalities, bitter, sweet, and amino acid, are mediated by G protein-coupled receptors that signal through a common transduction cascade: activation of phospholipase C beta2, leading to a breakdown of phosphatidylinositol-4,5-bisphosphate (PIP2) into diacylglycerol and inositol 1,4,5-trisphosphate, which causes release of Ca2+ from intracellular stores. The ion channel, TRPM5, is an essential component of this cascade; however, the mechanism by which it is activated is not known. Here we show that heterologously expressed TRPM5 forms a cation channel that is directly activated by micromolar concentrations of intracellular Ca2+ (K1/2 = 21 microM). Sustained exposure to Ca2+ desensitizes TRPM5 channels, but PIP2 reverses desensitization, partially restoring channel activity. Whole-cell TRPM5 currents can be activated by intracellular Ca2+ and show strong outward rectification because of voltage-sensitive gating of the channels. TRPM5 channels are nonselective among monovalent cations and not detectably permeable to divalent cations. We propose that the regulation of TRPM5 by Ca2+ mediates sensory activation in the taste system.Proceedings of the National Academy of Sciences 01/2004; 100(25):15160-5. · 9.68 Impact Factor