Sensory perception plays a vital role in the survival and well-being of animals, enabling them to navigate their environment and meet their fundamental requirements, such as securing nourishment, finding shelter, ensuring reproductive success, ensuring safety, and engaging in meaningful interactions with other members of their ecosystem. This complex procedure requires the synchronization of multiple separate sensory systems, each skilled in transmitting vital data to the brain for prompt analysis and reaction. Among these, mammals have evolved five primary sensory organs, namely the eye for vision, the ear for hearing, the tongue for taste, the nose for smell, and the skin for tactile perception, collectively facilitating the discernment of visual cues, auditory signals, flavors, scents, and tactile sensations. Much like other mammals, Drosophila melanogaster possesses distinct sensory organs that empower it to distinguish favorable from unfavorable environmental stimuli, enabling its survival. Drosophila exhibits a sophisticated sensory apparatus that aids in the recognition of external stimuli. Their remarkable compound eyes are particularly adept at facilitating various aspects of visual behavior, serving as a pivotal tool for environmental navigation and identification [1]. Furthermore, the species relies on the Johnston’s organ, situated within the antenna, which serves the dual purpose of detecting sounds and facilitating mechanosensation, thereby allowing fruit flies to respond to auditory and mechanical stimuli with precision ^[2][3][4][5][2,3,4,5]. In addition to these, Drosophila possesses a diverse array of olfactory organs, each specialized in the detection and processing of a wide range of odors [6]. These olfactory receptors play a critical role in the fly’s ability to identify and respond to specific volatile chemical cues within their surroundings. Moreover, the gustatory organs of the fruit fly enable the perception of taste, allowing them to differentiate between various food sources and potentially harmful substances ^{[7][8][9][10][11][12]}[7,8,9,10,11,12]. This intricate sensory system collectively equips Drosophila with the tools necessary for efficient perception and response to the external environment. Within the adult body of Drosophila, hair-like projections develop into taste organs in various locations, including the proboscis, legs, wing margins, and ovipositor ^{[13][14][15][16][17][18][19]}[13,14,15,16,17,18,19]. Of these, the tip of the proboscis comprises the bifurcate labellum, which plays a particularly crucial role in detecting taste by coming into contact with food or chemical compounds. The labellum of Drosophila contains 31 taste sensilla on each side, arranged symmetrically. These sensilla are instrumental in chemosensations, especially concerning non-volatile compounds. There are three distinct types of sensilla in the labellum, short (S-type), intermediate (I-type), and long (L-type), differentiated by their size ^[16][20][21][16,20,21]. Each sensillum is innervated by two to four gustatory receptor neurons (GRNs), one mechanosensory neuron, and three supporting cells, with their signals projected to the subesophageal zone (SEZ) of the brain, the region responsible for taste sensation ^{[13][22][23][24]}[13,22,23,24]. Additionally, taste sensation is also mediated by the hairless labellar taste peg situated between pseudotracheal rows, which is innervated by one chemosensory neuron and one mechanosensory neuron [25]. It is believed that taste pegs can only detect food when the flies open their labial palps. Furthermore, the adult fly pharynx, which acts as an internal molecular sensor, contains three different hairless internal taste organs: the dorsal cibarial sense organ (DCSO), the ventral cibarial sense organ (VCSO), and the labral sense organ (LSO) [26].

More precisely, the presence of specific molecular components like gustatory receptors (GRs) ^[7][27][7,27], ionotropic receptors (IRs) ^[28][29][28,29], pickpocket (PPK) ion channels ^[30][31][32][30,31,32], and transient receptor potential (TRP) ion channels ^[33][34][33,34] acts as mediators between external chemical cues and the fruit fly’s brain. These components play a crucial role in transducing chemical information into neural signals. The GRNs present in sensilla are sensitive to different types of chemical stimuli entering via pores at the tip of the sensilla. For example, the S-type sensilla contains four different GRNs, each responding to bitter or aversive compounds, sweet tastes, water, or specific minerals such as Na⁺ and Ca^{2+ [13][18][19][32]}[13,18,19,32]. In contrast, the L-type sensilla possesses four sets of GRNs that are sensitive to sweet tastes, water, low concentrations of salt, and others which have not yet been identified ^{[19][35][36][37][38]}[19,35,36,37,38]. Similarly, the I-type sensilla are equipped with two sets of GRNs responding to sweet and bitter compounds, including both low and high concentrations of salt ^[39][40][41][39,40,41]. In this intricate web of molecular and sensory interactions, Drosophila’s taste organs play a pivotal role in helping the fly navigate its environment, ensuring its sustenance and survival. These sensory mechanisms provide a fascinating window into the broader world of biological systems and their adaptation to complex ecological challenges.

Taste preferences in Drosophila also have profound ecological implications. They guide foraging behavior, influence food source selection, impact breeding site choices, and even contribute to competition and niche partitioning among different Drosophila populations. Drosophila’s taste neurons and receptors assess food sources, shaping their preferences and guiding foraging. Favorable food sources lead to concentrated fly populations, impacting resource distribution. Drosophila can also act as pollinators, spreading pollen from one plant to another as they feed on nectar, affecting plant ecology. Taste cues guide females to identify and select appropriate substrates for oviposition. Consequently, taste preferences influence the distribution of Drosophila larvae within their environment, impacting their development and survival. Diverse taste perception facilitates niche partitioning, enabling the coexistence of multiple Drosophila species by exploiting different food sources and reducing competition. Understanding these taste preferences is essential for unraveling the intricate ecological dynamics and interactions between these fruit flies and their environment.

Drosophila’s food preferences go beyond taste alone, influenced by nutritional needs, genetic variation, environmental conditions, and learned behavior. While taste guides their initial preferences, nutritional requirements can override taste, and genetic diversity affects their perception of specific compounds ^[42][43][51,52]. Environmental factors, like food availability and competition, also play a significant role. Drosophila can learn from experience, allowing them to adapt and make optimal food choices. These multifaceted factors ensure their adaptability and reproductive success in diverse environments.

Sourness, characterized by low pH or acidity, represents a fundamental taste sensation ^[44][53]. It is universally appealing in moderate concentrations, yet becomes unappealing at higher levels, across both vertebrate and invertebrate species ^{[45][46][47][48]}[54,55,56,57]. Conversely, foods with high pH or alkaline properties generally lack appeal ^[49][50][51][58,59,60]. Nevertheless, in mildly alkaline conditions, food with compounds like ammonia and certain amines is preferred, influenced by the intricacies of the sensory system ^[52][53][61,62] (Figure 1A). Notably, the attraction to mildly basic food is believed to be linked to the presence of low concentrations of salt ^[49][58]. Commonly, acidic components are found in raw fruits and spoiled food items, adding to the significance of detecting sourness as a warning sign. Conversely, basic or alkaline taste is triggered in certain vegetables, legumes, nuts, and other items due to their elevated pH levels. Current research across various species, both vertebrate and invertebrate, has substantiated that basic taste also qualifies as one of the fundamental taste qualities ^{[49][51][54][55][56]}[58,60,63,64,65].

2. Molecular Mechanism of Acid Sensation

The perception of sour taste, resulting from the presence of acidic compounds in food, has long intrigued scientists, leading to a gradual understanding of how the peripheral taste system in animals detects this taste, alongside other fundamental tastes. Due to variations in the chemical sensitivity of taste receptors among different animal species, identifying a single universal channel responsible for sour taste detection proved challenging ^[57][82]. A different study proposed a widely accepted theory that sour taste perception involves acid molecules breaching cell membranes to release hydrogen ions ^[58][59][91,92], activating sour taste receptors in specialized taste receptor cells (TRCs) on the tongue ^[60][61][93,94]. Throughout evolution, animals have developed a diverse array of proton-activated channels and G-protein-coupled receptors (GPCRs) to distinguish acidic pH levels. Various potential receptors were considered, including the acid-sensing ion channel 2 (ASIC2) ^[62][95] and hyperpolarization-activated cyclic nucleotide gated (HCN 1 and HCN 4) channels ^[63][64][96,97], but their roles were inconclusive ^[65][66][98,99]. Polycystic kidney disease 2-like 1 (PKD2L1) was initially thought to be a sour taste receptor ^[67][68][100,101], but further studies found its role to be modest ^[69][70][102,103]. Ultimately, Otopetrin 1 (OTOP1) emerged as a pivotal sensor in sour taste perception, marking a significant milestone in theour understanding of animal taste sensation ^[71][72][73][87,88,89] (Figure 1B). Further, researchers discovered that lowering extracellular pH increases inward current in Type III taste receptor cells, indicating their role in detecting sourness ^[74][104]. OTOP1 is identified as essential in sour taste transduction, with experiments confirming pH-dependent currents ^[71][74][87,104]. Cryo-EM analysis revealed OTOP1’s dimeric structure with 12 transmembrane helices ^[75][105]. The mechanism of OTOP1 gating for proton permeation remains unknown, warranting future research. Fruit flies possess Otopetrin-like a (Otop-La) as a functional ortholog of OTOP1 ^[46][47][55,56]. Otopetrins are a family of proteins that have been implicated in sour taste perception in various organisms, including mammals and fruit flies ^[46][47][55,56]. This protein is part of the molecular machinery that allows fruit flies to perceive and respond to sour tastes, ensuring their ability to make informed dietary choices. Understanding the presence of Otop-La in fruit flies adds to theour knowledge of the molecular mechanisms underlying sour taste perception in insects, contributing to theour broader understanding of taste sensation across different species. Behavioral analysis in fruit flies demonstrated a bidirectional response to diets with varying acid concentrations, showing attraction to low-acid and aversion to highly acidic food ^[45][48][76][54,57,106]. Electrophysiological analyses revealed that L-type sensilla were responsible for the attraction to acid-containing foods, while S-type sensilla were involved in exhibiting aversion ^[45][48][76][54,57,106]. Nevertheless, this outcome does not imply that L-type sensilla solely responds to attractive compounds such as low pH compound, while S-type sensilla is solely responsible for exhibiting neuronal response to aversive compounds like high pH compound. Researchers showed that IR7c-expressing GRNs, which are required to sense high concentrations of salt (aversive nature), are expressed in most of the L-type sensilla and few S-type sensilla [37]. This suggests that even L-type sensilla could serve as a neuronal responder, contributing to the detection of a compound known to induce aversive behavior. In addition, sensilla S4 and S8, akin to L-type sensilla, demonstrated heightened neuronal responses to appealing concentrations of salt, underscoring the likelihood that S-type sensilla also exhibited increased neuronal activity in response to enticing compounds ^[77][107]. Thus, different sensilla exhibit different neuronal response for various tastants, including acidic compounds, and the exact connectome between S-type and L-type sensilla is yet to be established.

3. Alkali Detection in Taste

Just as low pH (acidity) produces a gustatory sensation known as sourness, it is logical to hypothesize that high pH (alkalinity) might also elicit a distinct taste sensation. Early scientific inquiries suggested that alkali compounds could evoke specific types of tastes, such as sour and sweet, by exciting taste receptors ^[78][79][114,115]. For example, studies dating back to 1948 observed that the tip of the human tongue had a higher sensitivity to sodium hydroxide solution than other regions, providing early evidence for an alkaline taste sensation ^[54][63]. Electrophysiological recordings of taste nerves in cats also indicated that a subset of these nerves could be activated by high pH, suggesting the existence of an alkaline taste ^[55][64]. Trigeminal neurons, a type of sensory neurons, respond to various external alkaline pH levels ^[55][64]. Among the TRP channels, TRPV1 and TRPA1 are known to be activated by intracellular alkalization but not by exposure to external alkaline pH alone ^[80][81][116,117]. It is important to note that these channels can also be activated by acidic pH levels. In the context of studying C. elegans, TMC-1 plays a role in mediating alkaline sensation through ASH nociceptive neurons ^[82][118]. TMC-1 is one of the two TMC family genes found in C. elegans and is believed to encode a sodium-sensitive channel that is required for salt chemosensation and food signaling. When exposed to alkaline pH, ASH neurons exhibit an inward current that is primarily dependent on TMC-1 and only secondarily dependent on the TRPV channel OSM-9. While OSM-9/TRPV is sensitive to both acidic and basic pH, TMC-1 displays specificity towards alkaline conditions. It is essential not only for the electrical current in ASH neurons, but also for the behavioral response triggered by alkaline pH, whereas it is not involved in the response to acidic pH ^[82][118]. Research on carabid beetles and ground beetles demonstrated that these insects exhibit a strong aversion to alkaline conditions, particularly in relation to their habitats and food sources ^[83][119]. These studies suggested that insects have taste receptors that can detect high pH levels and influence their feeding behavior. Furthermore, this study holds ecological significance, as the aversion to alkaline conditions influences habitat selection, affects soil quality and vegetation composition, impacts community dynamics, and holds implications for conservation and land management practices across diverse ecosystems. It highlights the intricate web of interactions and dependencies that characterize ecological systems. In the context of Drosophila research, it was discovered that alkaline substances with a high pH could indeed generate a gustatory sensation, implying the presence of a separate channel in the taste organ dedicated to alkaline taste perception. Further investigation revealed the importance of a chloride channel called Alkaliphile (Alka) in fruit flies’ adverse taste reactions to basic foods (Figure 1E). Alka selectively creates a high pH-gated chloride channel in specific GRNs, enabling the detection of alkaline taste ^[49][58]. Additionally, it was found that high pH conditions suppressed the sugar-based neuronal response triggered by sweet-sensing GRNs, supporting the notion that the detection of high pH involves dual mechanisms: the activation of certain bitter-sensing GRNs and the inhibition of sweet-sensing GRNs. This discovery in fruit flies has paved the way for future studies exploring how other organisms’ peripheral taste organs perceive alkaline tastes at the molecular level. Additionally, research in vertebrates, specifically zebrafish, revealed the involvement of OTOP1 in basic taste sensation ^[51][60]. OTOP1 was found to mediate proton inflow and efflux in response to extracellular acid and base stimulation. Notably, the mutation of specific domains within OTOP1 affected its affinity for alkali compounds without impacting its response to acidic stimuli, highlighting the distinction between acid and alkali activation ^[51][60]. The mouse study demonstrated that OTOP1 functions as a sensor for ammonium chloride (NH₄Cl) ^[84][90]. Taste responses to NH₄Cl, as measured from isolated Type III TRCs or gustatory nerves, were significantly reduced or completely absent in an Otop1^−/− mouse. Recent research into the gustatory system using Drosophila and Aedes aegypti has found that the perception of sweetness and saltiness can be inhibited as the basicity (pH) of a tastant solution increases, particularly with the addition of ammonium hydroxide (NH₄OH) ^[50][59]. This intriguing discovery challenges theour understanding of taste, and holds potential implications for industries like food and beverage industries, as it suggests that altering basicity could influence flavor perception and innovation. In the context of acidic food conditions, an intriguing research avenue emerges with adaptability based on the changing condition of internal body state ^[85][113]. Exploring the impact of alkaline presence on internal states and consequent behavioral changes presents an exciting opportunity for investigation. Delving deeper, it becomes fascinating to examine how these state-dependent alterations influence the functioning of sensory neurons, particularly in the sugar and bitter circuits downstream. Additionally, a compelling aspect of this research could involve studying the switch in response to hunger levels. This may explain how organisms adapt to alkaline food, which could be considered a potentially aversive compound, yet may offer nutritional benefits in extreme conditions. The exploration of alkaline taste, like sour and other taste modalities, continues to unravel the intricacies of the gustatory system and how organisms perceive and respond to a wide range of chemical stimuli in their environment.