Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis

Drosophila’s white gene encodes an ATP-binding cassette G-subfamily (ABCG) half-transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w1118 mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w1118 learning phenotype is also found in the wapricot and wcoral alleles, is dominant, and is rescued by genomic white and mini-white transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while w1118 mutants were resistant to this deficit. The w1118 mutants displayed higher levels of cholesterol and cholesterol esters than wildtype under this low-cholesterol diet. Increasing levels of serotonin, dopamine, or both in the white mutants significantly improved w1118 learning. However, serotonin levels were not lower in the heads of the w1118 mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w1118 brain. We propose that the w1118 learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.

Compensatory variability in network parameters enhances memory performance in the Drosophila mushroom body

Neural circuits use homeostatic compensation to achieve consistent behavior despite variability in underlying intrinsic and network parameters. However, it remains unclear how compensation regulates variability across a population of the same type of neurons within an individual and what computational benefits might result from such compensation. We address these questions in the Drosophila mushroom body, the fly’s olfactory memory center. In a computational model, we show that under sparse coding conditions, memory performance is degraded when the mushroom body’s principal neurons, Kenyon cells (KCs), vary realistically in key parameters governing their excitability. However, memory performance is rescued while maintaining realistic variability if parameters compensate for each other to equalize KC average activity. Such compensation can be achieved through both activity-dependent and activity-independent mechanisms. Finally, we show that correlations predicted by our model’s compensatory mechanisms appear in the Drosophila hemibrain connectome. These findings reveal compensatory variability in the mushroom body and describe its computational benefits for associative memory.

Lipophorin receptors regulate mushroom bodies development and participate in learning, memory, and sleep in flies

Drosophila melanogaster Lipophorin Receptors, LpR1 and LpR2, mediate lipid uptake. The orthologs of these receptors in vertebrates, ApoER2 and VLDL-R, bind Reelin, a glycoprotein not present in flies. These receptors are associated with the development and function of the hippocampus and cerebral cortex, important association areas in the mammalian brain. It is currently unknown whether LpRs play similar roles in the Drosophila brain. We report that LpR-deficient flies exhibit impaired olfactory memory and sleep patterns, which seem to reflect anatomical defects found in a critical brain association area, the Mushroom Bodies (MB). Moreover, cultured MB neurons respond to mammalian Reelin by increasing the complexity of their neurites. This effect depends on LpRs and Dab, the Drosophila ortholog of the reelin signaling adaptor protein Dab1. In vitro, two of the long isoforms of LpRs allow the internalization of Reelin. Overall, these findings demonstrate that LpRs contribute to MB development and function, supporting the existence of LpR-dependent signaling in Drosophila.

Desflurane Does not Affect Post-Operative Short-Term Olfactory Memory of Patients Undergoing Laparoscopic Surgery Introduction: a prospective clinical study

Background: The purpose of our study was to evaluate the effect of 6% desflurane on short-term olfactory memory after laparoscopic surgery, and to investigate whether plasma concentrations of plasma S-100β protein, neuron specific enolase (NSE) and melatonin correlate with it.Methods: We collected medical data of patients who underwent laparoscopic surgery in the Second People's Hospital of Guiyang during May 2018 - February 2020. A total of 40 patients, who were aged 18-60 years old with American Society of Anesthesiologists (ASA) physical status I-II, were enrolled in the study. During the operation, the patients inhaled 6% desflurane to maintain the anesthesia. Patients were brought to the recovery room 45 minutes prior to the surgery (T0). And the patients were sent to the post-anesthesia care unit (PACU) after the surgery, if their Aldrete score was ≥ 9 points (T1), the CCCRC test was repeated to re-assess their olfactory memory. Venous blood samples (3 mL) were collected at T0 and T1, and the plasma was centrifuged at 3,000 rpm and then stored in a refrigerator at -20°C. Plasma S-100β protein, NSE, and melatonin levels were determined using ELISA.Results: There was no statistically significant difference in the odor identification score between T0 and T1 (P > 0.05). As compared with T0, the plasma concentrations of S-100β protein and NSE declined at T1. However, these differences were not statistically significant (P > 0.05). There were also no statistically significant changes in melatonin levels between T0 and T1 (P > 0.05）.Conclusions: This study found that undergoing general anesthesia with the inhaled anesthetic desflurane did not affect the short-term olfactory memory of patients undergoing laparoscopic surgery. This may be explained by the proposition that desflurane maintains plasma S-100β protein, NSE, and melatonin levels.Trial registration: Chinese Clinical Trial Registry (URL: http:// www.chictr.org.cn. Registry number: ChiCTR2100049441 ). Date of Registration: 2 August 2021.

Is Novelty Detection Important in Long-Term Odor Memory?

Memory for odors is believed to be longer-lasting than memory for visual stimuli, as is evidenced by flat forgetting curves. However, performance on memory tasks is typically weaker in olfaction than vision. Studies of odor memory that use forced-choice methods confound responses that are a result of a trace memory and responses that can be obtained through process of elimination. Moreover, odor memory is typically measured with common stimuli, which are more familiar and responses may be confounded by verbal memory, and measure memory in intentional learning conditions, which are ecologically questionable. Here we demonstrate the value of using tests of memory in which hit rate and correct rejection rate are evaluated separately (i.e., not using forced-choice methods) and uncommon stimuli are used. This study compared memory for common and uncommon odors and pictures that were learned either intentionally (Exp. 1) or incidentally (Exp. 2) and tested with either a forced-choice or a one-stimulus-at-a-time (“monadic”) recognition task after delays of 15 min, 48 h or 1 week. As expected, memory declined with delay in most conditions, but depended upon the particular measure of memory and was better for pictures than odors and for common than uncommon stimuli. For common odors, hit rates decreased with delay but correct rejection rates remained constant with delay. For common pictures, we found the opposite result, constant hit rates and decreased correct rejection rates. Our results support the ‘misfit theory of conscious olfactory perception’, which highlights the importance of the detection of novelty in olfactory memory and suggests that olfactory memory should be studied using more ecologically valid methods.

Olfactory Learning Supports an Adaptive Sugar-Aversion Gustatory Phenotype in the German Cockroach

An association of food sources with odors prominently guides foraging behavior in animals. To understand the interaction of olfactory memory and food preferences, we used glucose-averse (GA) German cockroaches. Multiple populations of cockroaches evolved a gustatory polymorphism where glucose is perceived as a deterrent and enables GA cockroaches to avoid eating glucose-containing toxic baits. Comparative behavioral analysis using an operant conditioning paradigm revealed that learning and memory guide foraging decisions. Cockroaches learned to associate specific food odors with fructose (phagostimulant, reward) within only a 1 h conditioning session, and with caffeine (deterrent, punishment) after only three 1 h conditioning sessions. Glucose acted as reward in wild type (WT) cockroaches, but GA cockroaches learned to avoid an innately attractive odor that was associated with glucose. Olfactory memory was retained for at least 3 days after three 1 h conditioning sessions. Our results reveal that specific tastants can serve as potent reward or punishment in olfactory associative learning, which reinforces gustatory food preferences. Olfactory learning, therefore, reinforces behavioral resistance of GA cockroaches to sugar-containing toxic baits. Cockroaches may also generalize their olfactory learning to baits that contain the same or similar attractive odors even if they do not contain glucose.

Olfactory Learning Supports an Adaptive Sugar-Aversion Gustatory Phenotype in the German Cockroach

An association of food sources with odors prominently guides foraging behavior in animals. To understand the interaction of olfactory memory and food preferences, we used glucose-averse (GA) German cockroaches. Multiple populations of cockroaches evolved a gustatory polymorphism where glucose is perceived as a deterrent and enables GA cockroaches to avoid eating glucose-containing toxic baits. Comparative behavioral analysis using an operant conditioning paradigm revealed that learning and memory guide foraging decisions. Cockroaches learned to associate specific food odors with fructose (phagostimulant, reward) within only a 1 hr conditioning session, and with caffeine (deterrent, punishment) after only three 1 hr conditioning sessions. Glucose acted as reward in wild type (WT) cockroaches, but GA cockroaches learned to avoid an innately attractive odor that was associated with glucose. Olfactory memory was retained for at least 3 days after three 1 hr conditioning sessions. Our results reveal that specific tastants can serve as potent reward or punishment in olfactory associative learning, which reinforces gustatory food preferences. Olfactory learning therefore reinforces behavioral resistance of GA cockroaches to sugar-containing toxic baits. Cockroaches may also generalize their olfactory learning to baits that contain the same or similar attractive odors even if they do not contain glucose.