scholarly journals Input connectivity reveals additional heterogeneity of dopaminergic reinforcement in Drosophila

2020 ◽  
Author(s):  
Nils Otto ◽  
Markus W. Pleijzier ◽  
Isabel C. Morgan ◽  
Amelia J. Edmondson-Stait ◽  
Konrad J. Heinz ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
List Type ◽  
Behavioral Experiments ◽  
State Dependent ◽  
Memory Extinction ◽  
Level Function ◽  
Output Neurons ◽  
Functional Relevance ◽  
Dendritic Branches

SummaryDifferent types of Drosophila dopaminergic neurons (DANs) reinforce memories of unique valence and provide state-dependent motivational control [1]. Prior studies suggest that the compartment architecture of the mushroom body (MB) is the relevant resolution for distinct DAN functions [2, 3]. Here we used a recent electron microscope volume of the fly brain [4] to reconstruct the fine anatomy of individual DANs within three MB compartments. We find the 20 DANs of the γ5 compartment, at least some of which provide reward teaching signals, can be clustered into 5 anatomical subtypes that innervate different regions within γ5. Reconstructing 821 upstream neurons reveals input selectivity, supporting the functional relevance of DAN sub-classification. Only one PAM-γ5 DAN subtype γ5(fb) receives direct recurrent input from γ5β’2a mushroom body output neurons (MBONs) and behavioral experiments distinguish a role for these DANs in memory revaluation from those reinforcing sugar memory. Other DAN subtypes receive major, and potentially reinforcing, inputs from putative gustatory interneurons or lateral horn neurons, which can also relay indirect feedback from MBONs. We similarly reconstructed the single aversively reinforcing PPL1-γ1pedc DAN. The γ1pedc DAN inputs mostly differ from those of γ5 DANs and they cluster onto distinct dendritic branches, presumably separating its established roles in aversive reinforcement and appetitive motivation [5, 6]. Tracing also identified neurons that provide broad input to γ5, β’2a and γ1pedc DANs suggesting that distributed DAN populations can be coordinately regulated. These connectomic and behavioral analyses therefore reveal further complexity of dopaminergic reinforcement circuits between and within MB compartments.HighlightsNanoscale anatomy reveals additional subtypes of rewarding dopaminergic neurons.Connectomics reveals extensive input specificity to subtypes of dopaminergic neurons.Axon morphology implies dopaminergic neurons provide subcompartment-level function.Unique dopaminergic subtypes serve aversive memory extinction and sugar learning.

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 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 Valence and State-Dependent Population Coding in Dopaminergic Neurons in the Fly Mushroom Body

2020 ◽  
Vol 30 (11) ◽  
pp. 2104-2115.e4 ◽  
Author(s):  
K.P. Siju ◽  
Vilim Štih ◽  
Sophie Aimon ◽  
Julijana Gjorgjieva ◽  
Ruben Portugues ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Population Coding ◽  
State Dependent

scholarly journals Transsynaptic mapping of Drosophila mushroom body output neurons

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kristin M Scaplen ◽  
Mustafa Talay ◽  
John D Fisher ◽  
Raphael Cohn ◽  
Altar Sorkaç ◽  
...  
Keyword(s):  
Associative Memory ◽  
Mushroom Body ◽  
Behavioral Responses ◽  
Previous Experience ◽  
Shaped Body ◽  
Functional Implications ◽  
Output Neurons ◽  
Functional Relevance ◽  
The Brain ◽  
Lateral Accessory Lobe

The mushroom body (MB) is a well-characterized associative memory structure within the Drosophila brain. Analyzing MB connectivity using multiple approaches is critical for understanding the functional implications of this structure. Using the genetic anterograde transsynaptic tracing tool, trans-Tango, we identified divergent projections across the brain and convergent downstream targets of the MB output neurons (MBONs). Our analysis revealed at least three separate targets that receive convergent input from MBONs: other MBONs, the fan-shaped body (FSB), and the lateral accessory lobe (LAL). We describe, both anatomically and functionally, a multilayer circuit in which inhibitory and excitatory MBONs converge on the same genetic subset of FSB and LAL neurons. This circuit architecture enables the brain to update and integrate information with previous experience before executing appropriate behavioral responses. Our use of trans-Tango provides a genetically accessible anatomical framework for investigating the functional relevance of components within these complex and interconnected circuits.

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 Differential Conditioning Produces Merged Long-term Memory in Drosophila

2021 ◽  
Author(s):  
Bohan Zhao ◽  
Jiameng Sun ◽  
Qian Li ◽  
Yi Zhong
Keyword(s):  
Conditioned Stimulus ◽  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Differential Conditioning ◽  
Long Term Memory ◽  
Single Trial ◽  
Kenyon Cells ◽  
Output Neurons ◽  
New Protein

AbstractMultiple spaced trials of aversive differential conditioning can produce two independent longterm memories (LTMs) of opposite valence. One is an aversive memory for avoiding the conditioned stimulus (CS+), and the other is a safety memory for approaching the non-conditioned stimulus (CS−). Here, we show that a single trial of aversive differential conditioning yields one merged LTM (mLTM) for avoiding both CS+ and CS−. Such mLTM can be detected after sequential exposures to the shock-paired CS+ and unpaired CS−, and be retrieved by either CS+ or CS−. The formation of mLTM relies on triggering aversive-reinforcing dopaminergic neurons and subsequent new protein synthesis. Expressing mLTM involves αβ Kenyon cells and corresponding approach-directing mushroom body output neurons (MBONs), in which similar-amplitude long-term depression of responses to CS+ and CS− seems to signal the mLTM. Our results suggest that animals can develop distinct strategies for occasional and repeated threatening experiences.

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.

scholarly journals Assembly of the Drosophila mushroom body circuit and its regulation by Semaphorin 1a

2019 ◽  
Author(s):  
Chen-Han Lin ◽  
Suewei Lin
Keyword(s):  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Molecular Mechanisms ◽  
Neural Circuit ◽  
Ectopic Expression ◽  
Cellular Mechanisms ◽  
Limited Effect ◽  
Output Neurons ◽  
Guidance Molecule

SummaryThe Drosophila mushroom body (MB) is a learning and memory center in the fly brain. It is the most extensively studied brain structure in insects, but we know little about the molecular and cellular mechanisms underlying assembly of its neural circuit. The MB is composed of around 2200 intrinsic Kenyon cells (KCs), whose axons are bundled to form multiple MB lobes. The MB lobes are innervated by a large number of extrinsic neurons. Twenty types of dopaminergic neurons (DANs) and 21 types of MB output neurons (MBONs) have been identified. Each type of these extrinsic neurons innervates specific compartments or zones in the MB lobes. Here, we characterize the assembly of the MB circuit and reveal several intriguing features of the process. The DANs and MBONs innervate zones in the MB vertical lobes in specific sequential orders. Innervation of DAN axons in some zones precedes that of MBON dendrites, and vice versa in other zones. MBON and DAN innervations are largely independent of each other. Removing one type of extrinsic neuron during early development has a limited effect on the MB lobe innervations of the other type of extrinsic neurons. However, KC axons are essential for zonal elaboration of DAN axons and MBON dendrites. Competition also exists between MB zones for some MBONs, so when the cognate zones for these MBONs are missing, their dendrites are misdirected to other zones. Finally, we identify Semaphorin 1a (Sema1a) as a crucial guidance molecule for MBON dendrites to innervate specific MB lobe zones. Ectopic expression of Sema1a in some DANs is sufficient to re-direct their dendrites to those zones, demonstrating a potential to rewire the MB circuit. Taken together, our work provides an initial characterization of the cellular and molecular mechanisms underlying MB circuit assembly.

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