In animals, social experience plays an important role in the adaptive modification of behavior. Previous social experience changes locomotor activity in Drosophila melanogaster. In females, suppression of locomotion is observed only when flies are in aggregations, but males retain a reduced level of locomotor activity up to 5 days after being isolated from the group. The mechanisms underlying such behavioral plasticity still largely are unknown. In this study, we aimed to identify new candidate genes involved in the social experience-dependent modification of locomotor activity. We tested the effect of social experience on spontaneous locomotor activity in various mutant males, including those with impaired learning and memory, circadian rhythms, some biochemical pathways, and sensory systems. The results of the present study indicate that the biogenic amines and olfactory perception appear to play key roles in social experience-induced changes in locomotor activity. Also, we performed a screen of the collection of mutants carrying random autosomal insertions of PdL transposon. We isolated five candidate genes, of which two genes, Dek and Hel89B, encode proteins related to the formation of the epigenetic code, implying that epigenetic factors regulating gene expression may be involved in social experience-dependent modification of locomotor behavior.

Social experience (housing in an unisexual group) modifies locomotor activity in Drosophila. In females, suppression of locomotion occurs only when flies are in aggregations [1], but males retain a lowered level of locomotor activity up to 5 days after their separation from a group [2]. The mechanism by which social experience (housing in a group) affects locomotor activity in Drosophila males is yet unknown. To study the genetic control and clarify the mechanisms of behavioral changes resulting from social experience, we have tested the locomotor activity modifications in various mutants, including those with impaired learning and memory, circadian rhythms, some biochemical pathways, and sensory systems. The results of the present study show that these changes do not seem to be based on the learning and memory mechanisms. The biogenic amines (dopamine and octopamine) seems to play a principal role in the changes in locomotor activity caused by social experience. Also, the dependence of this behavioral modification on olfactory perception was shown. This implies the possible participation of pheromones, which should be verified in future research. Also, with the same aim, we have performed the screening of our collection of mutants carrying random autosomal insertions of PdLtransposon. Five candidate genes presumably playing a role in behavioral modifications resulting from social experience were revealed (Dek, Hel89B, RpL41, CG11791 and NaCP60E). The results imply a possible role for epigenetic regulation of gene expression in the modification of locomotor behavior caused by social experience.

For about half a century Drosophila has served as a model subject in biomedical research in the influence of spaceflight factors on genome stability, lifespan, metabolism and immunity. Up to now behavioral investigations have been performed either with offspring of flies that had been to space or directly with flies onboard the International Space Station (ISS). Ours is the first research providing evidence that upon return to the Earth after the spaceflight to the ISS, drosophila males show impaired geotaxis, reduced locomotor activity and decreased courtship intensity. The behavioral changes retain for at least two weeks. The main stress factor during the spaceflight is microgravity. Under these conditions living organisms are less able to control posture and goal-directed movements. Microgravity disturbs warm air convection that may cause local changes in oxygen-carbon dioxide balance. This creates unfavorable conditions in vials worsening the physiological state of flies that may influence the results of postflight tests.

Living things have been evolving under certain parameters of the geomagnetic field. Many organisms are sensitive to electromagnetic fields and use them for spatial orientation and navigation during migration. The honeybee Apis mellifera L. is a convenient experimental model to study the biological effects of electromagnetic fields. The honeybees use the Earth’s magnetic field for orientation in space and mobilization for foraging. Recent decades have seen an emergence of numerous anthropogenic sources of electromagnetic radiation. They are likely to be stressors for bees and other insects. It is known the transcriptional activity changes as part of stress response, while histone acetylation is associated with transcription activation. The article reports the results of the study into H3K9/14 histone acetylation in the neurons (inner Kenyon cells) of mushroom body calyxes (structures responsible for learning and memory in insects) in the honeybee. It was shown that an increase in the natural geomagnetic field leads to a decrease in H3K9/14 histone acetylation. This indicates a decrease in transcriptional activity in mushroom bodies, which may affect cognitive and foraging activities of the honeybee.

Using an original method, we have received Drosophila melanogaster with a deficiency including a complete sequence of quick-to-court gene. In this report, we describe the behavioural features of this new deletion mutant. There were no serious deviations from the normal mating behaviour in flies with the deletion, but the behaviour of deletion mutants still had some features. Of all the elements, only the frequency of licking significantly increased in mutants. The duration of mating elements did not change in flies with deletion, and the latent period decreased only for following the female and licking. We have found that mutant males produce more courtship song than control males when courting Oregon R females as estimated by the pulse song index. In our experiment, mutant females provoked much less pulse song production by Oregon R males than control females do. Moreover, Oregon R males initiate courtship song towards mutant females later than towards control females. In other words, the study of pulse song production showed that the deficiency in females leads to a decrease in the intensity of courtship of wild-type males, whereas the deficiency in males leads to more intensive care for wild-type females.

Статья посвящена 70-летнему юбилею одной из генетических лабораторий Института физиологии им. И. П. Павлова — лаборатории сравнительной генетики поведения, на протяжении 70 лет неоднократно менявшей свое название: от лаборатории по переделке безусловных рефлексов (1 августа 1950 года), лаборатории физиологии низших животных, и, наконец, с 1965 года и поныне — лаборатории сравнительной генетики поведения. В статье освещен неоценимый научный теоретический вклад руководителей лаборатории — М. Е. Лобашева и В. В. Пономаренко. Это новые главы в учении И. П. Павлова «Биология и генетика условного рефлекса», по-новому раскрывшие значение механизма условного рефлекса в интеграции и координации процессов клеточной и тканевой дифференциации внутри многоклеточного организма; в онтогенетической адаптации к экстремальным факторам внешней среды, уводящей организм от элиминации естественным отбором; сигнальной наследственности, передачи индивидуального опыта между поколениями живых существ. Это концепция системной нейроэндокринной регуляции генетических и цитогенетических процессов, позволившая выделить особую роль состояния нервной системы (уровень ее возбудимости, тонуса по И. П. Павлову) в реализации генетической информации в отношении поведенческих признаков по принципу обратной связи в соответствии с текущими нуждами организма, влиянием условий внешней среды и индивидуальным опытом. Это использование мутаций гомологичных генов у представителей животного мира, стоящих на разных ступенях филогенетического развития, с целью изучения малоисследованных эндогенных нейроактивных соединений, таких как кинуренины. Мутации генов, контролирующих метаболизм цАМФ, были получены в лаборатории с использованием химического мутагенеза (Е. В. Савватеева, Н. Г. Камышев). Наконец, это выявление с использованием Р-инсерционного мутагенеза новых генов, контролирующих когнитивную и моторную деятельность, и изучение механизмов их влияния. Для этого создана современная методическая и приборная молекулярно-генетическая база, собственное программное обеспечение (Н. Г. Камышев), полная автоматизация регистрации поведения насекомых.

Previously, we described gene factor of interpulse interval (fipi, aka CG15630), whose decreased expression in the nervous system led to the changes in the parameters of a pulse song -a component of courtship in Drosophila males, in particular, to the reduction of the interpulse interval (Fedotov et al. 2014).In this study, we describe the structures of the nervous system, where the fipi gene is expressed.We also examine the role of this gene in courtship behavior, including its modification as a result of previous experience of a male courting a non-receptive fertilized female.It is known that such experience (learning) reduces the intensity of subsequent courtship of a male as regards other females.The expression of the GFP marker protein under control of the fipi gene promoter was detected in local interneurons of the antennal lobes, in Kenyon gamma-neurons, and in visual neurons of the optical lobes.The blocking of synaptic transmission from fipi neurons reduced the efficiency of courtship suppression, and increased the excitability of these neurons, which resulted in a longer retention of the suppression effect.The knockdown of the fipi gene did not cause abnormalities in the courtship suppression, instead, it increased courtship intensity in males with no experience.The results show that fipi neurons are involved in the regulation of courtship behavior, and suggest that the expression of the fipi gene in gamma-neurons of mushroom bodies is involved in the formation of a short-term memory in this form of learning.

Прогресс в области информационных технологий, средств глобальной беспроводной связи приводит к изменениям в естественном электромагнитном фоне Земли и экологической безопасности живых организмов. Представляется актуальным исследовать влияние техногенных и естественных электромагнитных полей c использованием модельных биологических объектов, включая медоносную пчелу, особо чувствительную к действию электромагнитных излучений (ЭМИ) в связи с врожденной необходимостью их использования в естественной среде обитания. Разрабатываемые системы защиты от ЭМИ за счет изменения характеристик излучения могут также вызывать специфические магнитобиологические реакции живых систем. В настоящей работе на медоносной пчеле (Apis mellifera L.) изучено влияние на врожденные и когнитивные компоненты поведения устройств — резонаторов ЭМИ, действующих изолированно и вкупе с Wi-Fi-роутером, а также изменений (ослабления/усиления) магнитного поля в месте проведения эксперимента относительно магнитного поля Земли. Показано угнетающее действие на процессы формирования памяти всех изучаемых факторов, кроме усиленного магнитного поля (стимулирующее воздействие). При этом наиболее глубокие изменения в процессы формирования памяти вносит изменение магнитных полей. Как ослабление, так и усиление магнитного поля значительно ингибирует долговременную память. Наблюдаемые изменения в процессах формирования памяти неизбежно отразятся на летной пищедобывательной активности и в целом на продуктивности семей медоносных пчел.

Results of behavioral tests made postflight after two independent travels of Drosophila melanogaster to International Space Station (ISS) are presented. In Experiment 1, the first instar larvae were launched, and the eclosed imagoes gave the next generation that developed from the egg at ISS. After return to Earth the behavior of adult males of the next generation was examined. In Experiment 2, the newly emerged adult males were launched and after 7.5 days of staying at ISS were tested in the lab. In Experiment 1, we found pronounced influence of development in Space on subsequent locomotor behavior of adult flies. In flies developed in Space, all three independent parameters of locomotor behavior (run frequency, run duration and running speed) were increased, at least at certain time points, during the first hour of registration. At the same time, the climbing ability of experimental flies was reduced. In Experiment 2, no changes in the climbing ability were detected. During the first 30 min after registration beginning the flown flies performed less frequent but more extended runs than the control flies did. However, later the flown flies demonstrated an increased run frequency. Additionally, the interpulse interval in the pulse courtship song was shorter in the flown males. Taken together, the results point to a considerable activation of the central nervous system in flies developed at the ISS and to a minor one in the adult flies travelled to the ISS. This shows that earlier stages of development are more sensitive to spaceflight factors than the adult stage.

Here, we describe the longevity and locomotor behavior of senescent Drosophila males with altered expression of Dgp-1 gene. In comparison with the wild-type Canton-S (CS) males, six characteristics of the phenotype of Dgp-1[843k] mutant were found: (1) low expression of isoform A; (2) augmented expression of isoform B; (3) reduction in the mean lifespan; (4) decrease in the running speed in 3-day-old flies; (5) maintenance of a high run frequency in senescent flies; and (6) resistance to heat stress manifested as maintenance of a high run frequency at 29 °C. After cessation of "cantonization" process, mean lifespan of the mutant males drifted from low to high values finally exceeding that for CS. In contrast, behavioral phenotype of the mutant was robust. Using the GAL4/UAS system, we showed that neurospecific overexpression of isoform B resulted in a slight decrease of longevity and a high level of run frequency in the senescent flies, similar to that in Dgp-1[843K] mutant. In addition, a decreased level of reactive oxygen species was found in Dgp-1[843K] mutant males maintained under stress conditions. The elevated resistance to oxidative stress probably explains the two distinctive features of the mutation: resistance to aging processes and thermal stress displayed at behavioral level.

We report a comparative analysis of the effect of alpha- and beta- isomers of the dipeptides aspartyl-serine and aspartyl-proline on the ability of honeybees to retain the conditioned food reflex to olfactory cues in their short-term/long-term memory. Stimulatory/inhibitory effects of the alpha-dipeptides on memory processes are confined to the concentration range of 10-6–10-8 M. In contrast, beta-dipeptides exert stimulatory/inhibitory effects on memory not only within the same range but also at ultra-low (pico- and femtomolar) concentrations. At concentrations of 10-9–10-11 M, beta-dipeptides have no effect on the characteristics under study (“silence zone”). Thus, we revealed fundamental differences in the effects of alpha- and beta- dipeptide isomers on the memory regulation.

We studied the effect of non-ionizing electromagnetic radiation (EMR) of a Wi-Fi router on sensory olfactory excitability, food motivation, and the ability to form a conditioned reflex (PER), and its retention in short-term and long-term memory in the honeybee. The bees were placed in a Faraday cage for various periods of time (up to 24 h), with the Wi-Fi router switched on (test) or off (control). A 24-hour impact of Wi-Fi EMR had a significant inhibitory effect on food excitability and short-term memory in honeybees. By contrast, long-term memory of honeybees insignificantly increased.

To study the central pattern generators functioning, previously we identified genes, whose neurospecific knockdowns led to deviations in the courtship song of Drosophila melanogaster males. Reduced expression of the gene CG15630 caused a decrease in the interpulse interval. To investigate the role of CG15630, which we have called here fipi (factor of interpulse interval), in the courtship song production, at first, we have characterized fipi transcripts and protein (FIPI) in the mutant flies carrying P insertion and deletions in this gene and in flies with its RNAi knockdown. FIPI is homologous to the mammalian NCAM2 protein, an important factor of neuronal development in the olfactory system. In this study, we have revealed that local fipi knockdown in the antennal olfactory sensory neurons (OR67d and IR84a), which are responsible for reception of chemosignals modulating courtship behavior, alters the interpulse interval in the opposite directions. Thus, a proper fipi expression seems to be necessary for perception of sexual chemosignals, and the effect of fipi knockdown on IPI value depends on the type of chemoreceptor neurons affected.

This study addresses the influence of combinations of two encoded amino acids with opposite, memory-inhibiting and memory-enhancing, effects on short-term and long-term memory formation in the honeybee. Experimentation was based on the classical proboscis extension response conditioning by a single-trial exposure to clove odor with a sucrose solution reward. The presence of the acquired conditioned response was tested 1 min (short-term memory) and 180 min (long-term memory) after the learning trial. The data obtained suggest a stimulatory (memory-enhancing) effect of the combination of two amino acids, individual effects of which are opposite. The stimulatory amino acid was present in the mixture in all the trials (8 combinations) at a subthreshold concentration, i.e. it did not influence memory formation. In some trials, the stimulatory effect of an amino acid mixture (for example, stimulatory aspartic acid combined with inhibitory lysine or serine) significantly exceeded that of a single stimulatory amino acid applied at a threshold concentration. Interestingly, the effect of amino acid combinations on memory formation in honeybees resembles their effect on cell proliferation in rat tissue explants of various origin.

Social interactions are able to strongly influence animal physiology and behavior. As is known, social experience can lead to changes in sexual and aggressive behavior, circadian rhythms and composition of cuticular hydrocarbons in Drosophila. Previously, we have shown that housing Drosophila males in monosexual groups of 20 individuals for 3 days after eclosion leads to a strong and long-term suppression of locomotor activity as revealed at individual testing, in contrast to males kept separately. The present research addressed courtship behavior, and specifically song production, in Drosophila males reared under similar conditions. It was found that rearing males in monosexual groups leads to a suppression of courtship and song production as well as to a simultaneous increase in locomotor activity when tested with a moving female. The latter effect was due to the strong urge of males to avoid interindividual contacts that prevented triggering the courtship ritual. It was suggested that intermale aggression caused by group rearing generates a state similar to conditioned fear.

Familial Alzheimer's disease (FAD) which leads to memory impairments is caused by mutations in presenilin-1 (PS1) gene in approximately 40% of cases. PS1 is well known as a component of the gamma-secretase enzyme which cleaves APP to A-beta. To become a catalytic part of enzyme PS1 undergoes an endoproteolysis. It was shown that mutations in PS1 gene disrupt endoproteolysis increasing uncleaved protein level in brain tissue of FAD patients. In our study we found effects of FAD PS1 mutants (PS1DE9, PS1 D247A) on activity of store-operated calcium (SOC) channels in mice hippocampal neurons and Neuro2a cell line. Increased uncleaved PS1 levels led to SOC channels hyperactivities detected with direct single-cell electrophysiological measurements and calcium imaging experiments with fura2-AM. The effects were caused by impaired signal transduction from ER to SOC channels in plasmatic membrane. The impaired intracellular signal transduction by STIM1 sensor was revealed in live confocal imaging experiments and proved with STIM1 knock-down. Moreover, a feeding of Drosophila melanogaster transgenes expressing human mutated PS1 in cholinergic nervous system with pharmacological inhibitor of STIM sensor signal transduction 2APB led to rescue of the memory loss detected by courtship based assay with aged animals. Therefore hyperactive STIM1 signal transduction leads to increased SOC channels activity which could be the reason for memory loss in FAD. This work was supported by the program of "Molecular and Cellular Biology" RAS, research grants from the Russian Basic Research Foundation, Russian Scientific Fund and the President of Russia Scholarship.