scholarly journals Dopamine neurons promotes wakefulness via the DopR receptor in the Drosophila mushroom body

2020 ◽  
Author(s):  
Margaret Driscoll ◽  
Steven Buchert ◽  
Victoria Coleman ◽  
Morgan McLaughlin ◽  
Amanda Nguyen ◽  
...  
Keyword(s):  
Mushroom Body ◽  
Critical Role ◽  
Fruit Fly ◽  
Dopamine Neurons ◽  
Central Complex ◽  
Behavioral Arousal ◽  
Sleep Homeostasis ◽  
Output Neurons ◽  
Gaba Transmission

AbstractNeural circuits involved in regulation of sleep play a critical role in sleep-wake transition and ability of an organism to engage in other behaviors critical for survival. The fruit fly, Drosophila melanogaster is a powerful system for the study of sleep and circuit mechanisms underlying sleep and co-regulation of sleep with other behaviors. In Drosophila, two neuropils in the central brain, mushroom body (MB) and central complex (CX) have been shown to influence sleep homeostasis and receive neuromodulator input critical to sleep-wake switch.Dopamine neurons (DANs) are the primary neuromodulator inputs to the MB but the mechanisms by which they regulate sleep- and wake-promoting neurons within MB are unknown. Here we investigate the role of subsets of DANs that signal wakefulness and project to wake-promoting compartments of the MB. We find that inhibition of specific subsets of PAM and PPL1 DANs projecting to the MB increase sleep in the presence of strong wake-inducing stimuli that reduces GABA transmission, although activity of these neurons is not directly modulated by GABA signaling. Of these subsets we find that DANs innervating the γ5 and β’2 MB compartments require both DopR1 and DopR2 receptors located in downstream Kenyon cells and mushroom body output neurons (MBONs). Further, we report that unlike the activity of wake-promoting MBONs and KCs, whose activity is modulated by sleep-need and PAM-DAN activity is independent of sleep-need. We have characterized a dopamine mediated sleep-circuit providing an inroad into understanding how common circuits within MB regulate sleep, wakefulness and behavioral arousal.

scholarly journals Compartment specific regulation of sleep by mushroom body requires GABA and dopaminergic signaling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Margaret Driscoll ◽  
Steven N Buchert ◽  
Victoria Coleman ◽  
Morgan McLaughlin ◽  
Amanda Nguyen ◽  
...  
Keyword(s):  
Mushroom Body ◽  
Fruit Fly ◽  
Dopamine Neurons ◽  
Central Complex ◽  
State Transitions ◽  
Sleep Regulation ◽  
Negative Valence ◽  
Sleep Homeostasis ◽  
Specific Regulation ◽  
Positive And Negative Valence

AbstractSleep is a fundamental behavioral state important for survival and is universal in animals with sufficiently complex nervous systems. As a highly conserved neurobehavioral state, sleep has been described in species ranging from jellyfish to humans. Biogenic amines like dopamine, serotonin and norepinephrine have been shown to be critical for sleep regulation across species but the precise circuit mechanisms underlying how amines control persistence of sleep, arousal and wakefulness remain unclear. The fruit fly, Drosophila melanogaster, provides a powerful model system for the study of sleep and circuit mechanisms underlying state transitions and persistence of states to meet the organisms motivational and cognitive needs. In Drosophila, two neuropils in the central brain, the mushroom body (MB) and the central complex (CX) have been shown to influence sleep homeostasis and receive aminergic neuromodulator input critical to sleep–wake switch. Dopamine neurons (DANs) are prevalent neuromodulator inputs to the MB but the mechanisms by which they interact with and regulate sleep- and wake-promoting neurons within MB are unknown. Here we investigate the role of subsets of PAM-DANs that signal wakefulness and project to wake-promoting compartments of the MB. We find that PAM-DANs are GABA responsive and require GABAA-Rdl receptor in regulating sleep. In mapping the pathways downstream of PAM neurons innervating γ5 and β′2 MB compartments we find that wakefulness is regulated by both DopR1 and DopR2 receptors in downstream Kenyon cells (KCs) and mushroom body output neurons (MBONs). Taken together, we have identified and characterized a dopamine modulated sleep microcircuit within the mushroom body that has previously been shown to convey information about positive and negative valence critical for memory formation. These studies will pave way for understanding how flies balance sleep, wakefulness and arousal.

scholarly journals Predictive olfactory learning in Drosophila

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chang Zhao ◽  
Yves F. Widmer ◽  
Sören Diegelmann ◽  
Mihai A. Petrovici ◽  
Simon G. Sprecher ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Trace Conditioning ◽  
Fruit Fly ◽  
Olfactory Learning ◽  
Shock Strength ◽  
Behavioral Experiments ◽  
Kenyon Cells ◽  
Output Neurons

AbstractOlfactory learning and conditioning in the fruit fly is typically modelled by correlation-based associative synaptic plasticity. It was shown that the conditioning of an odor-evoked response by a shock depends on the connections from Kenyon cells (KC) to mushroom body output neurons (MBONs). Although on the behavioral level conditioning is recognized to be predictive, it remains unclear how MBONs form predictions of aversive or appetitive values (valences) of odors on the circuit level. We present behavioral experiments that are not well explained by associative plasticity between conditioned and unconditioned stimuli, and we suggest two alternative models for how predictions can be formed. In error-driven predictive plasticity, dopaminergic neurons (DANs) represent the error between the predictive odor value and the shock strength. In target-driven predictive plasticity, the DANs represent the target for the predictive MBON activity. Predictive plasticity in KC-to-MBON synapses can also explain trace-conditioning, the valence-dependent sign switch in plasticity, and the observed novelty-familiarity representation. The model offers a framework to dissect MBON circuits and interpret DAN activity during olfactory learning.

scholarly journals Predictive olfactory learning in Drosophila

2019 ◽  
Author(s):  
Chang Zhao ◽  
Yves F Widmer ◽  
Soeren Diegelmann ◽  
Mihai Petrovici ◽  
Simon G Sprecher ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Trace Conditioning ◽  
Fruit Fly ◽  
Olfactory Learning ◽  
Shock Strength ◽  
Behavioral Experiments ◽  
Kenyon Cells ◽  
Output Neurons

AbstractOlfactory learning and conditioning in the fruit fly is typically modelled by correlation-based associative synaptic plasticity. It was shown that the conditioning of an odor-evoked response by a shock depends on the connections from Kenyon cells (KC) to mushroom body output neurons (MBONs). Although on the behavioral level conditioning is recognized to be predictive, it remains unclear how MBONs form predictions of aversive or appetitive values (valences) of odors on the circuit level. We present behavioral experiments that are not well explained by associative plasticity between conditioned and unconditioned stimuli, and we suggest two alternative models for how predictions can be formed. In error-driven predictive plasticity, dopaminergic neurons (DANs) represent the error between the predictive odor value and the shock strength. In target-driven predictive plasticity, the DANs represent the target for the predictive MBON activity. Predictive plasticity in KC-to-MBON synapses can also explain trace-conditioning, the valence-dependent sign switch in plasticity, and the observed novelty-familiarity representation. The model offer a framework to dissect MBON circuits and interpret DAN activity during olfactory learning.

scholarly journals Building a functional connectome of the Drosophila central complex

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Romain Franconville ◽  
Celia Beron ◽  
Vivek Jayaraman
Keyword(s):  
Light Microscopy ◽  
Critical Role ◽  
Central Complex ◽  
Connectivity Matrix ◽  
Insect Brain ◽  
Cell Type ◽  
Functional Connectome ◽  
Wide Range ◽  
Microscopy Images

The central complex is a highly conserved insect brain region composed of morphologically stereotyped neurons that arborize in distinctively shaped substructures. The region is implicated in a wide range of behaviors and several modeling studies have explored its circuit computations. Most studies have relied on assumptions about connectivity between neurons based on their overlap in light microscopy images. Here, we present an extensive functional connectome of Drosophila melanogaster’s central complex at cell-type resolution. Using simultaneous optogenetic stimulation, calcium imaging and pharmacology, we tested the connectivity between 70 presynaptic-to-postsynaptic cell-type pairs. We identified numerous inputs to the central complex, but only a small number of output channels. Additionally, the connectivity of this highly recurrent circuit appears to be sparser than anticipated from light microscopy images. Finally, the connectivity matrix highlights the potentially critical role of a class of bottleneck interneurons. All data are provided for interactive exploration on a website.

scholarly journals The connectome of the adult Drosophila mushroom body: implications for function

2020 ◽  
Author(s):  
Feng Li ◽  
Jack Lindsey ◽  
Elizabeth C. Marin ◽  
Nils Otto ◽  
Marisa Dreher ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Experimental Studies ◽  
Central Complex ◽  
Sensory Inputs ◽  
Descending Neurons ◽  
Sensory Modalities ◽  
Output Neurons ◽  
Transfer Of Information ◽  
Adult Drosophila

AbstractMaking inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome, and extensive prior experimental studies of its roles in learning, memory and activity regulation. Here we identify new components of the MB circuit in Drosophila, including extensive visual input and MB output neurons (MBONs) with direct connections to descending neurons. We find unexpected structure in sensory inputs, in the transfer of information about different sensory modalities to MBONs, and in the modulation of that transfer by dopaminergic neurons (DANs). We provide insights into the circuitry used to integrate MB outputs, connectivity between the MB and the central complex and inputs to DANs, including feedback from MBONs. Our results provide a foundation for further theoretical and experimental work.

A pair of dopamine neurons mediate chronic stress signals to induce learning deficit in Drosophila melanogaster

2021 ◽  
Vol 118 (42) ◽  
pp. e2023674118
Author(s):  
Jia Jia ◽  
Lei He ◽  
Junfei Yang ◽  
Yichun Shuai ◽  
Jingjing Yang ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Chronic Stress ◽  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Dopamine Neurons ◽  
Learning Deficit ◽  
Dopaminergic Activity ◽  
Output Neurons ◽  
Stress Signals ◽  
Underlying Mechanisms

Chronic stress could induce severe cognitive impairments. Despite extensive investigations in mammalian models, the underlying mechanisms remain obscure. Here, we show that chronic stress could induce dramatic learning and memory deficits in Drosophila melanogaster. The chronic stress–induced learning deficit (CSLD) is long lasting and associated with other depression-like behaviors. We demonstrated that excessive dopaminergic activity provokes susceptibility to CSLD. Remarkably, a pair of PPL1-γ1pedc dopaminergic neurons that project to the mushroom body (MB) γ1pedc compartment play a key role in regulating susceptibility to CSLD so that stress-induced PPL1-γ1pedc hyperactivity facilitates the development of CSLD. Consistently, the mushroom body output neurons (MBON) of the γ1pedc compartment, MBON-γ1pedc>α/β neurons, are important for modulating susceptibility to CSLD. Imaging studies showed that dopaminergic activity is necessary to provoke the development of chronic stress–induced maladaptations in the MB network. Together, our data support that PPL1-γ1pedc mediates chronic stress signals to drive allostatic maladaptations in the MB network that lead to CSLD.

scholarly journals Circuits that encode and predict alcohol associated preference

2019 ◽  
Author(s):  
Kristin M. Scaplen ◽  
Mustafa Talay ◽  
Sarah Salamon ◽  
Kavin M. Nuñez ◽  
Amanda G. Waterman ◽  
...  
Keyword(s):  
Memory Consolidation ◽  
Mushroom Body ◽  
Neural Circuits ◽  
Population Level ◽  
Dopamine Neurons ◽  
Behavioral Choice ◽  
Neuron Activation ◽  
Reward Delivery ◽  
Output Neurons ◽  
Insight Into

AbstractSubstance use disorders are chronic relapsing disorders often impelled by enduring memories and persistent cravings. Alcohol, as well as other addictive substances, remolds neural circuits important for memory to establish obstinate preference despite aversive consequences. How pertinent circuits are selected and shaped to result in these unchanging, inflexible memories is unclear. Using neurogenetic tools available inDrosophila melanogasterwe define how circuits required for alcohol associated preference shift from population level dopaminergic activation to select dopamine neurons that predict behavioral choice. During memory expression, these dopamine neurons directly, and indirectly via the mushroom body (MB), modulate the activity of interconnected glutamatergic and cholinergic output neurons. Transsynaptic tracing of these output neurons revealed at least two regions of convergence: 1) a center of memory consolidation within the MB implicated in arousal, and 2) a structure outside the MB implicated in integration of naïve and learned responses. These findings provide a circuit framework through which dopamine neuron activation shifts from reward delivery to cue onset, and provides insight into the inflexible, maladaptive nature of alcohol associated memories.

scholarly journals The connectome of the adult Drosophila mushroom body provides insights into function

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Feng Li ◽  
Jack W Lindsey ◽  
Elizabeth C Marin ◽  
Nils Otto ◽  
Marisa Dreher ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Experimental Studies ◽  
Central Complex ◽  
Sensory Inputs ◽  
Descending Neurons ◽  
Sensory Modalities ◽  
Output Neurons ◽  
Transfer Of Information ◽  
Adult Drosophila

Making inferences about the computations performed by neuronal circuits from synapse-level connectivity maps is an emerging opportunity in neuroscience. The mushroom body (MB) is well positioned for developing and testing such an approach due to its conserved neuronal architecture, recently completed dense connectome, and extensive prior experimental studies of its roles in learning, memory and activity regulation. Here we identify new components of the MB circuit in Drosophila, including extensive visual input and MB output neurons (MBONs) with direct connections to descending neurons. We find unexpected structure in sensory inputs, in the transfer of information about different sensory modalities to MBONs, and in the modulation of that transfer by dopaminergic neurons (DANs). We provide insights into the circuitry used to integrate MB outputs, connectivity between the MB and the central complex and inputs to DANs, including feedback from MBONs. Our results provide a foundation for further theoretical and experimental work.

scholarly journals Learning with reward prediction errors in a model of the Drosophila mushroom body

2019 ◽  
Author(s):  
James E. M. Bennett ◽  
Andrew Philippides ◽  
Thomas Nowotny
Keyword(s):  
Mushroom Body ◽  
Dopamine Neurons ◽  
Prediction Errors ◽  
Reward Prediction ◽  
Decision Outcomes ◽  
Effective Decision ◽  
Output Neurons ◽  
Constrained Model ◽  
Effective Decision Making ◽  
Reinforcing Stimuli

AbstractEffective decision making in a changing environment demands that accurate predictions are learned about decision outcomes. In Drosophila, such learning is or-chestrated in part by the mushroom body (MB), where dopamine neurons (DANs) signal reinforcing stimuli to modulate plasticity presynaptic to MB output neurons (MBONs). Here, we extend previous MB models, in which DANs signal absolute rewards, proposing instead that DANs signal reward prediction errors (RPEs) by utilising feedback reward predictions from MBONs. We formulate plasticity rules that minimise RPEs, and use simulations to verify that MBONs learn accurate reward predictions. We postulate as yet unobserved connectivity, which not only overcomes limitations in the experimentally constrained model, but also explains additional experimental observations that connect MB physiology to learning. The original, experimentally constrained model and the augmented model capture a broad range of established fly behaviours, and together make five predictions that can be tested using established experimental methods.

scholarly journals Drosophila mushroom bodies integrate hunger and satiety signals to control innate food-seeking behavior

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Chang-Hui Tsao ◽  
Chien-Chun Chen ◽  
Chen-Han Lin ◽  
Hao-Yu Yang ◽  
Suewei Lin
Keyword(s):  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Energy State ◽  
Fruit Fly ◽  
Mushroom Bodies ◽  
Kenyon Cells ◽  
Control Food ◽  
Seeking Behavior ◽  
Output Neurons ◽  
Food Seeking

The fruit fly can evaluate its energy state and decide whether to pursue food-related cues. Here, we reveal that the mushroom body (MB) integrates hunger and satiety signals to control food-seeking behavior. We have discovered five pathways in the MB essential for hungry flies to locate and approach food. Blocking the MB-intrinsic Kenyon cells (KCs) and the MB output neurons (MBONs) in these pathways impairs food-seeking behavior. Starvation bi-directionally modulates MBON responses to a food odor, suggesting that hunger and satiety controls occur at the KC-to-MBON synapses. These controls are mediated by six types of dopaminergic neurons (DANs). By manipulating these DANs, we could inhibit food-seeking behavior in hungry flies or promote food seeking in fed flies. Finally, we show that the DANs potentially receive multiple inputs of hunger and satiety signals. This work demonstrates an information-rich central circuit in the fly brain that controls hunger-driven food-seeking behavior.

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