Punishment Prediction by Dopaminergic Neurons in Drosophila

Sleep in Drosophila shares many features with mammalian sleep, but it remains unknown whether spontaneous and evoked activity of individual neurons change with the sleep/wake cycle in flies as they do in mammals. Here we used calcium imaging to assess how the Kenyon cells in the fly mushroom bodies change their activity and reactivity to stimuli during sleep, wake, and after short or long sleep deprivation. As before, sleep was defined as a period of immobility of >5 min associated with a reduced behavioral response to a stimulus. We found that calcium levels in Kenyon cells decline when flies fall asleep and increase when they wake up. Moreover, calcium transients in response to two different stimuli are larger in awake flies than in sleeping flies. The activity of Kenyon cells is also affected by sleep/wake history: in awake flies, more cells are spontaneously active and responding to stimuli if the last several hours (5-8 h) before imaging were spent awake rather than asleep. By contrast, long wake (≥29 h) reduces both baseline and evoked neural activity and decreases the ability of neurons to respond consistently to the same repeated stimulus. The latter finding may underlie some of the negative effects of sleep deprivation on cognitive performance and is consistent with the occurrence of local sleep during wake as described in behaving rats. Thus, calcium imaging uncovers new similarities between fly and mammalian sleep: fly neurons are more active and reactive in wake than in sleep, and their activity tracks sleep/wake history.T he fundamental features that characterize mammalian sleep also define Drosophila melanogaster sleep (1-3). Most crucially, in both flies and mammals, sleep is distinguished from simple rest (quiet wake) by an increased arousal threshold, i.e., a reduced ability to respond to external stimuli. Moreover, in flies and mammals sleep is controlled homeostatically by the duration as well by the intensity of prior wake, suggesting basic similarities in the mechanisms of sleep regulation across species. Thus, in flies both sleep deprivation and a rich learning experience lead to a sleep rebound characterized by overall increased sleep time, increased arousal threshold, and longer sleep episodes (4-6). As in mammals, overall neuronal activity in flies is also high during wake and low during sleep (6-8). Specifically, a seminal study using local field potential (LFP) recordings from the Drosophila medial protocerebrum found high spike-like potentials that disappeared after the block of synaptic transmission in the mushroom bodies (MBs) (7). This high spike activity was present when flies were moving or had been quiescent for only a few seconds, but disappeared with sleep (i.e., after periods of immobility >5 min), when the overall LFP power in all frequencies also decreased by ∼60% (7). The study concluded that neural activity in the sleeping fly brain, or at least in a central region spanning the MBs, resembles that seen in mammals in several brainstem cell groups including noradrenergic ne...

Section: Discussionmentioning

confidence: 99%

Sleep- and wake-dependent changes in neuronal activity and reactivity demonstrated in fly neurons using in vivo calcium imaging

Bushey

Tononi

Cirelli

2015

“…In Drosophila, dopaminergic neurons that project to the mushroom bodies respond strongly to electric shock (38). Compromising the function of these neurons impairs aversion learning in the fruit fly (15), and pharmacological analyses suggest the same may be true in other insects (39), including bees (40), which raises the interesting possibility that QMP, through its actions on dopamine pathways, might have an impact not only on activity levels, but also on aversion learning in young workers.…”

Section: Discussionmentioning

confidence: 99%

Queen pheromone modulates brain dopamine function in worker honey bees

Beggs

Glendining²,

Marechal³

et al. 2007

150

139

Honey bee queens produce a sophisticated array of chemical signals (pheromones) that influence both the behavior and physiology of their nest mates. Most striking are the effects of queen mandibular pheromone (QMP), a chemical blend that induces young workers to feed and groom the queen and primes bees to perform colony-related tasks. But how does this pheromone operate at the cellular level? This study reveals that QMP has profound effects on dopamine pathways in the brain, pathways that play a central role in behavioral regulation and motor control. In young worker bees, dopamine levels, levels of dopamine receptor gene expression, and cellular responses to this amine are all affected by QMP. We identify homovanillyl alcohol as a key contributor to these effects and provide evidence linking QMPinduced changes in the brain to changes at a behavioral level. This study offers exciting insights into the mechanisms through which QMP operates and a deeper understanding of the queen's ability to regulate the behavior of her offspring.Apis mellifera ͉ biogenic amines ͉ neuroethology ͉ neuromodulation ͉ pheromonal communication C omplex social interactions require systems of communication that are reliable and unambiguous. The honey bee, Apis mellifera, employs Ͼ50 substances to communicate with and to organize its colony, and the information that is conveyed between colony members is both subtle and sophisticated (1-3).Maintaining colony organization is a primary role of the queen, whose pheromones enable her to regulate not only the behavior but also the physiology of her nest mates. The most striking effects are those of queen mandibular pheromone (QMP), a chemical blend that induces young workers to feed and groom the queen (Fig. 1) and primes bees to perform colonyrelated tasks (4, 5). The retinue of workers that attend the queen facilitates the distribution of QMP throughout the colony, where it inhibits the rearing of new queens (6), helps prevent the development of worker ovaries (7), influences comb-building activities, (8) and affects the biosynthesis of juvenile hormone (9) [and hence the age-related behavioral ontogeny of recipient workers (10)]. Despite QMP's central role in the normal functioning and organization of honey bee colonies, very little is known about the cellular mechanisms through which it operates.We were intrigued by one of the key components of QMP, homovanillyl alcohol (HVA) (4). HVA (4-hydroxy-3-methoxyphenylethanol) bears a striking structural resemblance to dopamine (see Fig. 1 Right), a biogenic amine that plays a central role in insect behavioral regulation and motor control (11-18). The presence of this compound within the pheromone blend suggested to us that dopamine function in the brain of recipient bees might be affected by exposure to QMP. To test this hypothesis, we exposed young workers to QMP and examined its effects on brain dopamine levels, levels of dopamine receptor gene expression, and cellular responses to this amine. The results provide compelling evidence that QMP al...

“…The MB model of olfactory short-term memory in Drosophila (17) proposes that output synapses of the KCs representing the CS ϩ increase their gain in the course of conditioning to drive a MB output neuron (conditioned response). Two recent reports (21,22) describe extrinsic MB neurons in the MB output region displaying the properties expected of such output neurons. For this model to work outside of the laboratory, the representation of the CS ϩ in the MBs has to be, at least to some extent, concentration invariant.…”

Section: Discussionmentioning

confidence: 99%

Distinct memories of odor intensity and quality in Drosophila

Mašek

Heisenberg²

2008

Even in a simple Pavlovian memory task an animal may form several associations that can be independently assessed by the appropriate tests. Studying conditioned odor discrimination of the fruit fly Drosophila melanogaster we found that animals store quality and intensity of an odor as separate memory traces. The trace of odor intensity is short-lived, decaying in <3 h. Only the last intensity value is stored. In contrast to odor-quality memory, odor-intensity memory does not require the rutabaga-dependent cAMP signaling pathway. Flies rely on their memory of intensity in a narrow concentration range in which they can generalize intensity. Larger concentration differences they treat like different qualities. This study shows that the perceptual identity of an odor is based on at least three lines of processing in the brain: (i) a memory of odor quality, (ii) a memory of odor intensity, and (iii) a range of intensities (and qualities), in which the odor is generalized.A scent is characterized by its quality and whether it is intense or faint. Quality signals chemical properties of the source; intensity serves, among others, in orientation. Yet, for some odorants quality and quantity are not fully separated: At sufficiently different concentrations the same odorant may appear as distinct qualities (1).Flies (Drosophila melanogaster) are attracted by some odors and repelled by others. They can be trained to discriminate between different odorants (ref. 2 and for review see ref.3) and also between concentrations of a single odorant (4, 5). These findings alone do not prove that flies perceive and store the quality of an odor independently of its intensity. They might distinguish between ''good'' and ''bad'' and otherwise treat qualities and intensities as one and the same (6). The strongest evidence against this latter idea stems from a generalization experiment by Borst (5). Using two-component mixtures of odorants (A and B) Borst showed that flies treated mixtures differing in the ratio of A/B as more different from mixtures in which the ratio A/B had been kept constant but concentrations were changed. Apparently, flies like humans perceive both the quality of an odor and its intensity.Surprisingly, this confounding problem has been largely neglected. Evidently, if quality and intensity are perceived separately, they are likely to also be stored as distinct memory traces with different properties. In this case, much of what we know about olfactory learning in Drosophila needs to be specified as to whether it applies to odor quality, intensity, or both.Here, we characterize (short-term) olfactory memory (7) with respect to odor intensity (OIM) and odor quality (OQM). It is experimentally difficult to present two odorants at the same (fly-subjective) intensity, whereas it is easy to present the same odorant at different intensities. Therefore, we focus on odorintensity learning and look at odor-quality learning only indirectly by comparing odor-intensity learning to two-odor learning. As flies can exploit odor gradie...