Unilateral ephaptic program underlying sweetness dominance

• DOI: 10.1101/2023.08.04.551918
• Publication Date: 2023-08-08T18:15:18Z
• Authors: MinHyuk Lee; Seon Yeong Kim; Taeim Park; Kyeung Min Joo; Jae Young Kwon; Kyuhyung Kim; KyeongJin Kang

AbstractIn ephaptic coupling, physically adjacent neurons influence one another’s activity via the electric fields they generate. To date, the molecular mechanisms that mediate and modulate ephaptic coupling’s effects remain poorly understood. Here, we show that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel lateralizes the potentially mutual ephaptic inhibition betweenDrosophilagustatory receptor neurons (GRNs). While sweet-sensing GRNs (sGRNs) engage in ephaptic suppression of the adjacent bitter-sensing GRNs (bGRNs), HCN expression in sGRNs enables them to resist ephaptic suppression from the bGRNs. Such one-sided ephaptic inhibition confers sweetness dominance, facilitating ingestion of bitter-laced sweets. Flies with HCN-deficient sGRNs exhibited dramatically decreased attraction to sucrose mixed with moderate levels of caffeine, highlighting the behavioral significance that gustatory ephaptic inhibition promotes ingestion of carbohydrates buried in bitterness. Our findings indicate a role for the gating of ephaptic coding to ensure the intake of the essential nutrient despite bitter contaminants present in the feeding niche ofDrosophila, as the gating establishes a hierarchy of gustatory neuron excitation. Such refinement provides a previously unappreciated mechanism for controlling the activity of a neuronal network with potential implications in the mammalian brain, given the evolutionary conservation of the HCN genes.