Large conductance potassium (BK) channels are among the most sensitive molecular targets of ethanol. Whether the action of ethanol at BK channels influences the motivation to drink alcohol remains to be determined. In the present study, we sought to investigate the behavioral relevance of this interaction by introducing in the mouse genome a point mutation (BK α K361N) known to render BK channels insensitive to ethanol while preserving their physiological function. We demonstrate that preventing ethanol′s interaction with BK channels at this site hinders the escalation of voluntary alcohol intake induced by repeated cycles of alcohol intoxication and withdrawal. In contrast, the mutation does not alter ethanol′s acute behavioral effects, nor the metabolic and activity changes induced by chronic exposure to alcohol. Our findings point at BK channel ethanol-sensing capacity as a vulnerability mechanism in the transition from moderate alcohol consumption to pathological patterns of alcohol abuse.

Grapheme–color synesthetes experience graphemes (e.g., letters of the alphabet) as having a specific, consistent color. Most studies of grapheme–color synesthesia have only examined synesthetes in English, leaving underexplored the question of how synesthetic phenomenology might differ in languages that do not use alphabets. In particular, grapheme–color synesthesia in an abugida (a segmental writing system in which vowels are added to consonant graphemes using ‘accent’-like diacritical marks) has never been studied. Here, we present a case study of a Bengali synesthete, MJ, the first report of a grapheme–color synesthete in an abugida. First, we show that for MJ, diacritics influence the overall color of the consonant grapheme they modify, ‘pulling’ it toward the color she experiences for the vowel. Second, we describe and analyze the complex synesthetic experiences reported by MJ for conjunct graphemes, a unique orthographic feature of Brahmi-derived scripts (such as Bengali) in which multiple graphemes are visually combined into a single ‘merged’ grapheme. Finally, we show that in addition to these language-specific features, MJ’s synesthetic associations are influenced by some of the same linguistic properties (such as orthography and phonology) that influence synesthetic associations in other languages. We conclude that the idiosyncratic features of MJ’s synesthesia reflect unique properties of the Bengali writing system, that more studies of synesthesia in non-alphabetic scripts are needed, and that synesthetic phenomenology can offer insights into how linguistic properties shape grapheme representation in the brain.