Nonassociative Learning Research Articles

Heterogeneous stimuli induced nonassociative learning behavior in ZnO nanowire memristor

Nonassociative learning is a biologically essential and evolutionarily adaptive behavior in organisms. The bionic simulation of nonassociative learning based on electronic devices is essential to the neuromorphic computing. In this work, nonassociative learning is mimicked by a ZnO nanowire memristor without any other peripheral control circuit. The memristor demonstrates habituation and sensitization behaviors at the electrical and optical stimuli. Typical network-level parametric characteristics of habituation in neuroscience are realized in the memristor. When the heterogeneous stimuli are applied coincidentally, sensitization pulse could be identified by the exceptional response current. The results show that the natural selection rules could be simulated by the current single memristor. A possible mechanism based on the trapping states and adsorption of oxygen at the interface of Au/ZnO is proposed. The implementation of nonassociative learning in a single memristor device paves the way for building neuromorphic systems by simple electronic devices.

Learning processes in elementary nervous systems§.

Invertebrate animal models show simple behaviors supported by neural circuits easily accessible for experimentation and yet complex enough to provide necessary information on the cellular and molecular mechanisms that govern the vertebrate nervous system's function. The mechanisms underlying simple forms of learning have been extensively studied in the marine gastropod Aplysia californica, in which elementary non-associative learning of the behavioral habituation and sensitization type has been studied using the gill withdrawal reflex. A strong stimulus applied to the neck or tail improves the reflex response through heterosynaptic facilitation. The neurotransmitter serotonin is involved in both behavioral sensitization and dishabituation by acting through the second messenger cyclic adenosine monophosphate, protein kinase A, the phosphorylation of a K+ channel, causing its closure. This broadens the action potential profile, increases the influx of Ca2+ through voltage-gated Ca2+ channels, and enhances the neurotransmitter glutamate's release. Short-term memory is based on covalent modifications of pre-existing proteins, while long-term memory requires gene transcription, protein translation and growth of new synapses. Another simple invertebrate model is the leech Hirudo medicinalis. In nearly-intact preparations, the repetitive application of light electrical stimuli at the level of the caudal portion of the body wall can induce the habituation of swimming induction. At the same time, the stroke on the dorsal skin generates behavioral sensitization or dishabituation. Knowledge of the molecular mechanisms of activity-dependent forms of synaptic plasticity provides a basis for understanding the mechanisms underlying learning, memory, other forms of brain plasticity, and pathological conditions and suggests potential therapeutic interventions.

Supplemental Material for Exposure to Violence and Nonassociative Learning Capability Confer Risk for Violent Behavior

Supplemental Material for Exposure to Violence and Nonassociative Learning Capability Confer Risk for Violent Behavior

Exposure to Conspecific and Heterospecific Sex-Pheromones Modulates Gustatory Habituation in the Moth Agrotis ipsilon.

In several insects, sex-pheromones are essential for reproduction and reproductive isolation. Pheromones generally elicit stereotyped behaviors. In moths, these are attraction to conspecific sex-pheromone sources and deterrence for heterospecific sex-pheromone. Contrasting with these innate behaviors, some results in social insects point toward effects of non-sex-pheromones on perception and learning. We report the effects of sex-pheromone pre-exposure on gustatory perception and habituation (a non-associative learning) in male Agrotis ipsilon moths, a non-social insect. We also studied the effect of Z5-decenyl acetate (Z5), a compound of the sex-pheromone of the related species Agrotis segetum. We hypothesized that conspecific sex-pheromone and Z5 would have opposite effects. Pre-exposure to either the conspecific sex-pheromone or Z5 lasted 15 min and was done either immediately or 24 h before the experiments, using their solvent alone (hexane) as control. In a sucrose responsiveness assay, pre-exposure to the conspecific sex-pheromone had no effect on the dose-response curve at either delays. By contrast, Z5 slightly improved sucrose responsiveness 15 min but not 24 h after pre-exposure. Interestingly, the conspecific sex-pheromone and Z5 had time-dependent effects on gustatory habituation: pre-exposing the moths with Z5 hindered learning after immediate but not 24-h pre-exposure, whereas pre-exposure to the conspecific sex-pheromone hindered learning at 24-h but not immediate pre-exposure. They did not have opposite effects. This is the first time a sex-pheromone is reported to affect learning in a non-social insect. The difference in modulation between conspecific sex-pheromone and Z5 suggests that con- and hetero-specific sex-pheromones act on plasticity through different cerebral pathways.

Co-existence of ethanol-related respiratory and motivational learning processes based on a tactile discrimination procedure in neonatal rats.

In rats, high ethanol doses during early postnatal life exert deleterious effects upon brain development that impact diverse social and cognitive abilities. This stage in development partially overlaps with the third human gestational trimester, commonly referred to as the brain growth spurt period. At this stage in development, human fetuses and rat neonates (postnatal days [PD] 3-9) exhibit relatively high respiratory rates that are affected by subteratogenic ethanol doses. Recent studies suggest conditioned breathing responses in the developing organism, given that there are explicit associations between exteroceptive stimuli and the state of ethanol intoxication. Furthermore, studies performed with near-term rat fetuses suggest heightened sensitivity to ethanol's motivational effects. The present study was meant to analyze the unconditioned effects of ethanol intoxication and the possible co-occurrence of learning mechanisms that can impact respiratory plasticity, and to analyze the preference for cues that signal the state of intoxication as well as the effects of the drug, related with motor stimulation. Neonatal rats were subjected to differential experiences with salient tactile cues explicitly paired or not paired with the effects of vehicle or ethanol (2.0g/kg). A tactile discrimination procedure applied during PDs 3, 5, 7, and 9 allowed the identification of the emergence of ethanol-derived non-associative and associative learning processes that affect breathing plasticity, particularly when considering apneic disruptions. Ethanol was found to partially inhibit the disruptions that appeared to be intimately related with stressful circumstances defined by the experimental procedure. Tactile cues paired with the drug's effects were also observed to exert an inhibitory effect upon these breathing disruptions. The level of contingency between a given tactile cue and ethanol intoxication also resulted in significant changes in the probability of seeking this cue in a tactile preference test. In addition, the state of intoxication exerted motor-stimulating effects. When contrasting the data obtained via the analysis of the different dependent variables, it appears that most ethanol-derived changes are modulated by positive and/or negative (anti-anxiety) reinforcing effects of the drug. As a whole, the study indicates co-existence of ethanol-related functional changes in the developing organism that simultaneously affect respiratory plasticity and preference patterns elicited by stimuli that signal ethanol's motivational effects. These results emphasize the need to consider significant alterations due to minimal ethanol experiences that argue against "safe" levels of exposure in a critical stage in brain development.

Inconscients et Mémoires : considérations sur les recherches en neurosciences et l’approche freudienne de ces notions

The word of “memory” is such a complex and rich concept. But behind this simple word, a lot of different memories have been divided during last decades. Different models have been established like the Tulving's model or the Squire's model but there are still lot of researches about different kind of memories. It's such a specific domain that there are many studies about specific memories like declarative memory with the semantic memory and the episodic memory, or non-declarative memory which includes procedural memory, priming and perceptual learning or non-associative learning. Each specific memory is a wonderful and limitless perspective of researches and new discoveries. But we must add to these distinctions between all this kind of memories, the difference between a conscious or an unconscious treatment of the information stocked in memories. Due to the studies of these phenomenons, we are about to go further in comprehension of memory's working. With neurosciences and cognitive psychology, we can use the concept of “cognitive unconscious” and, with Freud and his conception of memory, we can still summon this other unconscious that we have to define as “Freudian”. Because this is a real issue to understand how the unconscious and obviously memory have an influence on conscious life. Like Freud said, many acts, many choices, even many sentences when we speak consciously, have a curious origin. What we are interested in is the understanding of the relation between elements stored in memories, such as episodic memory, semantic memory, or autobiographical memory, and the specific moment of awareness. Then we must include processes like sorting, weighting and selecting information. At last, we must add the fundamental question in Freudian theory: the influence of unconscious mental life on our acts and our conscious thoughts. Thus armed, we can study the singularity of the conscious answer, its specificity and the multiple influences that participated in its emergence. Memories, especially because they are based on a partially unconscious mode, are precious to understand the cognitive as well as subjective mechanisms that lead to consciousness. They allow to study brain's mechanisms, but also to ask the question of the causality of conscious mental life. Then, we can go further in these reflections on memory studying how from neural functions to elaborate and conscious metacognitive work, subjectivity emerge in every human being. Because through the different memories, the Freudian unconscious and consciousness we can try to understand how the accumulation of elements lead to an original and singular answer that would be the possible signature of subjectivity in human kind.

Influence of biological sex on social behavior, individual recogntion, and non-associative learning in the adult gray short-tailed opossum (Monodelphis domestica)

Social behavior is critical for relationship formation and is influenced by myriad environmental and individual factors. Basic and preclinical research typically relies on rodent models to identify the mechanisms that underlie behavior; however, it is important to use non-rodent models as well. A major objective of the present study was to test the hypothesis that biological sex and social experience modulate the expression of social behavior in the adult gray short-tailed opossum (Monodelphis domestica), a non-traditional model. We also investigated the non-associative learning abilities of these animals. Following a period of social isolation, animals of both sexes were paired with a non-familiar, same-sex partner for 10 min on three different occasions, with 24-hour inter-trial intervals. We are the first research group to find significant sex differences in submissive and nonsocial behaviors in Monodelphis. Females displayed significantly higher durations of nonsocial behavior that increased over trials. Males were more aggressive; their latencies to the first attack and submissive behavior decreased over trials whereas these latencies increased for females; males' duration of submissive behavior increased over trials whereas it decreased for females. A different group of subjects habituated in response to repeated presentations to neutral odors and dishabituated in response to novel odors. In addition, both males and females demonstrated the ability to form social memories in a standard individual (social) recognition test. Our results contribute to the characterization of this marsupial species, an important first step in developing it as a model of complex social behaviors.

Comorbidities of early-onset temporal epilepsy: Cognitive, social, emotional, and morphologic dimensions

Epilepsy, the most common neurologic disorder in childhood, is associated with a subset of psychiatric dysfunctions, including cognitive deficits, and alterations in emotionality (e.g., anxiety and depression) and social functioning. In the present study, we evaluated an integrative set of behavioral responses, including cognitive/socio-cognitive and emotional dimensions, using a number of behavioral paradigms in the LiCl/pilocarpine model of status epilepticus (SE) in rats. The aims of the study were to examine whether SE affects: 1) non-associative learning (habituation of exploratory behavior); 2) investigatory response to an indifferent stimulus object; 3) sociability/social novelty preference; 4) social recognition or discrimination; and 4) short- and long-term memory in the Morris water maze (MWM). Finally, we investigated the morphology of key brain structures involved in the examined behavioral dysfunctions. SE did not affect habituation to an open-field arena in juvenile (P25), adolescent (P32), or adult (P80) rats. SE rats spent less time in the central part of the arena. SE adolescent rats (P32) displayed a higher number of rearings with a shorter duration. SE rats displayed a markedly attenuated investigatory response to an indifferent stimulus object. SE rats in all age groups demonstrated pronounced deficits in sociability and the preference for social novelty. In addition, SE rats spent a reduced amount of time investigating a juvenile rat upon first exposure. After 30 min re-exposure together with an additional, novel juvenile, the SE rats spent equal time investigating both juveniles. In the MWM task, acquisition was unimpaired but there was a deficit in delayed memory retention after 10 days. SE did not affect cognitive flexibility expressed by reversal learning. Together, these findings suggest that early-life SE leads to alterations in emotional/anxiety-related behavior and affects sociability/preference for social novelty and social discrimination. Early-life SE did not alter acquisition of spatial learning, but it impaired delayed retention. Using Fluoro Jade B staining performed 24 h after SE revealed apparent neurodegeneration in the dorsal hippocampus, mediodorsal thalamic nucleus and medial amygdala, brain areas that are critically involved in network underlying emotional behavior and cognitive functions.

On the Generalization of Habituation: How Discrete Biological Systems Respond to Repetitive Stimuli

Habituation, a form of non-associative learning, isno longer studied exclusively within the fields of psychology and neuroscience. Indeed, the same stimulus-response pattern is observed at the molecular, cellular, and organismal scales and is not dependent upon the presence of neurons. Hence, a more inclusive theory is required to accommodate aneural forms of habituation. Here an abstraction of the habituation process that does not rely upon particular biological pathways or substrates is presented. Instead, five generalizable elements that define the habituation process are operationalized. The formulation can be applied to interrogate systems as they respond to several stimulation paradigms, providing new insights and supporting existing behavioral data. The model can be used to deduce the relative contribution of elements that contribute to the measurable output of the system. The results suggest that habituation serves as a general biological strategy that any system can implement to adaptively respond to harmless, repetitive stimuli.

Domain-Specific Cognitive Impairments in Humans and Flies With Reduced CYFIP1 Dosage

BackgroundDeletions encompassing a four-gene region on chromosome 15 (BP1-BP2 at 15q11.2), seen at a population frequency of 1 in 500, are associated with increased risk for schizophrenia, epilepsy, and other common neurodevelopmental disorders. However, little is known in terms of how these common deletions impact cognition. MethodsWe used a Web-based tool to characterize cognitive function in a novel cohort of adult carriers and their noncarrier family members. Results from 31 carrier and 38 noncarrier parents from 40 families were compared with control data from 6530 individuals who self-registered on the Lumosity platform and opted in to participate in research. We then examined aspects of sensory and cognitive function in flies harboring a mutation in Cyfip, the homologue of one of the genes within the deletion. For the fly studies, 10 or more groups of 50 individuals per genotype were included. ResultsOur human studies revealed profound deficits in grammatical reasoning, arithmetic reasoning, and working memory in BP1-BP2 deletion carriers. No such deficits were observed in noncarrier spouses. Our fly studies revealed deficits in associative and nonassociative learning despite intact sensory perception. ConclusionsOur results provide new insights into outcomes associated with BP1-BP2 deletions and call for a discussion on how to appropriately communicate these findings to unaffected carriers. Findings also highlight the utility of an online tool in characterizing cognitive function in a geographically distributed population.

Rewarded placebo analgesia: A new mechanism of placebo effects based on operant conditioning

Placebo analgesia is explained by two learning processes: classical conditioning and observational learning. A third learning process, operant conditioning, has not previously been investigated as a mechanism of placebo effects. We aimed to induce placebo analgesia by operant conditioning. Three groups of participants received electrocutaneous pain stimuli of the same intensity, preceded by either an orange or blue stimulus. In the conditioning phase of the study, participants from the experimental group were rewarded for low pain responses following one of the colour stimuli (placebo) and for high pain responses following the other colour stimuli (non-placebo). Moreover, they were punished when their pain responses were high following placebo stimuli and low following non-placebo stimuli. To investigate the role of contingency, that is dependent relation between rewards/punishers and pain responses, the random-control group received rewards and punishers in a non-contingent manner. The colour-control group did not receive any rewards or punishers to control for nonassociative learning. Pain intensity ratings were used as an outcome measure, and verbal feedback on pain ratings was used as rewards/punishers. When rewarding and punishment were stopped, only participants from the experimental group experienced less pain following the placebo than following the non-placebo stimuli; that is, placebo analgesia was found in this group. This effect was not extinguished during the study. Placebo analgesia can be induced by operant conditioning, which should be considered a third mechanism for producing placebo effects. Moreover, the contingency between pain responses and rewards/punishers is crucial to induce placebo analgesia through operant conditioning. According to the current placebo literature, placebo analgesia can be explained by two learning processes: classical conditioning and observational learning. A third learning process, operant conditioning, has not previously been investigated as a mechanism of placebo effects. Our study reveals that patients can learn placebo analgesia as a result of operant conditioning, suggesting that randomized controlled trials could be improved by controlling the reinforcement that might occur spontaneously when patients interact with, for example, medical personnel.

Accessing Olfactory Habituation in Drosophila melanogaster with a T-maze Paradigm.

Habituation is the process whereby perceptual changes alter the value of environmental stimuli, enabling salience filtering. This behavioral response decrement is a form of non-associative learning, where the subject learns about the stimulus and does not involve sensory adaptation, sensory or motor fatigue. The range of behavioral responses in D. melanogaster led to the development of a number of habituation paradigms addressing various sensory modalities. Habituation of osmotactic responses has previously been measured with the Y-maze test and required 30 min of odor exposure. Here, we describe an olfactory habituation assay utilizing the widely used in associative learning paradigms T-maze. Continuous or repetitive odor exposure for 4 min is adequate to attenuate osmotactic responses both to attractive and aversive odors. Importantly, the decreased response conforms to habitation parameters, presenting dishabituation and spontaneous recovery. This assay allows the study of habituation after brief odor exposure, but also discriminates between the two distinct phases of the response, an initial habituation latency period followed by habituation. In addition, the characterization of the neuronal circuits implicated in each phase facilitates further study of the molecular components underlying this process.

Dorsal hippocampal damage disrupts the auditory context-dependent attenuation of taste neophobia in mice.

Rodents exhibit neophobia for novel tastes, demonstrated by an initial reluctance to drink novel-tasting, potentially-aversive solutions. Taste neophobia attenuates across days if the solution is not aversive, demonstrated by increased consumption as the solution becomes familiar. This attenuation of taste neophobia is context dependent, which has been demonstrated by maintained reluctance to drink the novel tasting solution if the subject has to drink it after being brought to a novel environment. This spatial context-dependent attenuation of taste neophobia has been described and likely depends on the integrity of the dorsal hippocampus because this brain area is crucial for representing space and spatial context associations, but is unnecessary for processing taste memories per se. Whether changing the non-spatial auditory context causes a similar effect on attenuation of taste neophobia and the potential role of the dorsal hippocampus in processing this decidedly non-spatial information has not been determined. Here we demonstrate that changing the non-spatial auditory context affects the attenuation of taste neophobia in mice, and investigate the consequence of hippocampal lesion. The results demonstrate that the non-spatial auditory context-dependent attenuation of taste neophobia in mice is lost following NMDA excitotoxic lesions of the CA1 region of the dorsal hippocampus. These findings demonstrate that the dorsal hippocampus is crucial for the modulation non-associative taste learning by auditory context, neither of which provide information about space.

Insights into the roles of CMK-1 and OGT-1 in interstimulus interval-dependent habituation in Caenorhabditis elegans.

Habituation is a ubiquitous form of non-associative learning observed as a decrement in responding to repeated stimulation that cannot be explained by sensory adaptation or motor fatigue. One of the defining characteristics of habituation is its sensitivity to the rate at which training stimuli are presented-animals habituate faster in response to more rapid stimulation. The molecular mechanisms underlying this interstimulus interval (ISI)-dependent characteristic of habituation remain unknown. In this article, we use behavioural neurogenetic and bioinformatic analyses in the nematode Caenorhabiditis elegans to identify the first molecules that modulate habituation in an ISI-dependent manner. We show that the Caenorhabditis elegans orthologues of Ca2+/calmodulin-dependent kinases CaMK1/4, CMK-1 and O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, both function in primary sensory neurons to inhibit habituation at short ISIs and promote it at long ISIs. In addition, both cmk-1 and ogt-1 mutants display a rare mechanosensory hyper-responsive phenotype (i.e. larger mechanosensory responses than wild-type). Overall, our work identifies two conserved genes that function in sensory neurons to modulate habituation in an ISI-dependent manner, providing the first insights into the molecular mechanisms underlying the universally observed phenomenon that habituation has different properties when stimuli are delivered at different rates.

Individual differences in learning and biogenic amine levels influence the behavioural division between foraging honeybee scouts and recruits.

Animals must effectively balance the time they spend exploring the environment for new resources and exploiting them. One way that social animals accomplish this balance is by allocating these two tasks to different individuals. In honeybees, foraging is divided between scouts, which tend to explore the landscape for novel resources, and recruits, which tend to exploit these resources. Exploring the variation in cognitive and physiological mechanisms of foraging behaviour will provide a deeper understanding of how the division of labour is regulated in social insect societies. Here, we uncover how honeybee foraging behaviour may be shaped by predispositions in performance of latent inhibition (LI), which is a form of non-associative learning by which individuals learn to ignore familiar information. We compared LI between scouts and recruits, hypothesizing that differences in learning would correlate with differences in foraging behaviour. Scouts seek out and encounter many new odours while locating novel resources, while recruits continuously forage from the same resource, even as its quality degrades. We found that scouts show stronger LI than recruits, possibly reflecting their need to discriminate forage quality. We also found that scouts have significantly elevated tyramine compared to recruits. Furthermore, after associative odour training, recruits have significantly diminished octopamine in their brains compared to scouts. These results suggest that individual variation in learning behaviour shapes the phenotypic behavioural differences between different types of honeybee foragers. These differences in turn have important consequences for how honeybee colonies interact with their environment. Uncovering the proximate mechanisms that influence individual variation in foraging behaviour is crucial for understanding the ecological context in which societies evolve.

Habituation of Somatosensory Event-Related Potentials in Subthreshold Rhythmic (1 Hz) Electrocutaneous Stimulation of the Arm during the Slow-Wave Stage of Daytime Sleep

Previous studies have shown that low-frequency subthreshold electrocutaneous stimulation of the arm during deep slow-wave sleep in humans improves sleep quality. The main cognitive processes are known to operate during sleep, and use of event-related potentials is the main method for analysis of these processes. The aims of the present work were to study the characteristics of somatosensory event-related potentials (sERP) on rhythmic (1 Hz) subthreshold electrocutaneous volley stimulation of the arm during the slow-wave stage of daytime sleep and to evaluate the potential for habituation of sERP to rhythmic stimulation during sleep. Subthreshold stimulation during sleep produced somatosensory event-related potentials (ERP) (group mean, n = 16) in which three long-latency components could be identifi ed, which were more marked in the frontal lead of the contralateral hemisphere. Comparison of sERP averaged from the beginning and end of the volley of stimuli (30 stimuli) demonstrated signifi cant decreases in the amplitudes of all sERP components by the end of the volley. It is suggested that the decrease in sERP amplitude in slow-wave sleep is due to the simplest form of stimulus-dependent nonassociative learning - habituation.

A non-selective serotonin antagonist promotes rapid habituation in the terrestrial hermit crab.

Research has indicated that serotonin (5-HT) modulates non-associative learning in a variety of invertebrate species. Recent work has demonstrated that the terrestrial hermit crab is a suitable animal model for non-associative learning phenomena, including habituation, sensitization, and dishabituation. We examined the potential role of a non-selective 5-HT antagonist, methysergide, in non-associative learning in the hermit crab. We administered methysergide prior to delivering repeated stimulus presentations of a looming visual predator. We found evidence for more rapid habituation relative to a control condition in which crabs did not receive the drug. These results indicate a role for 5-HT in the defensive behavior of the hermit crab and importantly, suggest a conserved role for 5-HT in modulating basic learning processes in invertebrates.

Learning mechanisms in memristor networks based on GaN nanomembranes

We demonstrate experimentally that single crystalline GaN nanomembranes arranged in simple networks exhibit learning mechanisms such as habituation and dishabituation followed by storage of the response to a certain electrical stimulus. These artificial learning mechanisms are analogous to non-associative learning processes which are identical in simple animals and human beings. We found that the learning time depends on the number of GaN membranes in parallel, and this parameter decreases by 30% when three memristors are connected in parallel compared to the learning time of a single memristor. Moreover, an increased number of parallel memristors reduces the eventual asymmetry in the temporal response of the circuit at positive and negative step voltages.

Misophonia and Potential Underlying Mechanisms: A Perspective.

There is a growing research interest in the diagnosis rate of misophonia, a condition characterized by a negative emotional/autonomic reaction to specific everyday sounds. Diagnosis of misophonia requires a thorough case history and audiological test procedures. Associative and non-associative learning models for understanding the underlying mechanisms of misophonia have been presented. Currently, there is no cure or pharmaceutical agent for misophonia; however, therapy programs addressing misophonia and its characteristics do exist. Investigation of comorbid conditions and other psychological therapy strategies might help to reveal more about the underlying mechanisms and potentially lead to a successful treatment method.

Synaptic depression induced by postsynaptic cAMP production in the Drosophila mushroom body calyx.

Synaptic potentiation in Drosophila is observed at cholinergic synapses between antennal lobe (AL) and mushroom body (MB) neurons in the adult brain; however, depression at the AL-MB synapses has not yet been identified. By ex vivo Ca2+ imaging in an isolated cultured Drosophila brain, we found novel activity-dependent depression at the AL-MB synapses. The degree of Ca2+ responses after repetitive AL stimulation is significantly reduced in the dendritic region of MB neurons (calyx) compared with those before AL stimulation, and this reduction of Ca2+ responses remains for at least 30min. The expression of rutabaga, which encodes Ca2+ /calmodulin-dependent adenylyl cyclase, is essential in the MB neurons for the reduction of Ca2+ responses in the calyx. Our study reveals that elevation of cAMP production in the calyx during repetitive AL stimulation induces the depression at the AL-MB synapses. Synaptic plasticity has been studied to reveal the molecular and cellular mechanisms of associative and non-associative learning. The fruit fly Drosophila melanogaster can be used to identify the molecular mechanisms of synaptic plasticity because vast genetic information or tools are available. Here, by ex vivo Ca2+ imaging of an isolated cultured Drosophila brain, we examined the novel activity-dependent synaptic depression between the projection neurons of the antennal lobe (AL) and mushroom body (MB). Ex vivo Ca2+ imaging analysis revealed that electrical stimulation of AL elicits Ca2+ responses in the dendritic (calyx) and axonal (α lobe) regions of MB neurons, and the responses are reduced after repetitive AL stimulation. Since the cAMP signalling pathway plays an important role in synaptic plasticity in invertebrates and vertebrates, we examined whether the reduction of Ca2+ responses is also regulated by the cAMP signalling pathway. The expression of rutabaga (rut), which encodes Ca2+ /calmodulin-dependent adenylyl cyclase, was essential for the reduction of Ca2+ responses in the calyx and α lobe. Furthermore, imaging analysis using a fluorescence resonance energy transfer-based cAMP indicator revealed that the cAMP level increased in the wild-type calyx during repetitive AL stimulation, whereas it decreased in rut1 mutant flies with a loss-of-function mutation of rut. Thus, our study suggests that an increase in postsynaptic cAMP level during repetitive AL stimulation contributes to the attenuation of inputs at AL-MB synapses.