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 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 Modeling Uncertainty-Seeking Behavior Mediated by Cholinergic Influence on Dopamine

2019 ◽  
Author(s):  
Marwen Belkaid ◽  
Jeffrey L. Krichmar
Keyword(s):  
Decision Making ◽  
Dopaminergic Neurons ◽  
Cholinergic System ◽  
Dopamine Neurons ◽  
Comprehensive Understanding ◽  
Dopaminergic Activity ◽  
Integrate And Fire ◽  
Major Implication ◽  
Seeking Behavior

AbstractRecent findings suggest that acetylcholine mediates uncertainty-seeking behaviors through its projection to dopamine neurons – another neuromodulatory system known for its major implication in reinforcement learning and decision-making. In this paper, we propose a leaky-integrate-and-fire model of this mechanism. It implements a softmax-like selection with an uncertainty bonus by a cholinergic drive to dopaminergic neurons, which in turn influence synaptic currents of downstream neurons. The model is able to reproduce experimental data in two decision-making tasks. It also predicts that i) in the absence of cholinergic input, dopaminergic activity would not correlate with uncertainty, and that ii) the adaptive advantage brought by the implemented uncertainty-seeking mechanism is most useful when sources of reward are not highly uncertain. Moreover, this modeling work allows us to propose novel experiments which might shed new light on the role of acetylcholine in both random and directed exploration. Overall, this study thus contributes to a more comprehensive understanding of the roles of the cholinergic system and its involvement in decision-making in particular.

scholarly journals Increased Mesohippocampal Dopaminergic Activity and Improved Depression-Like Behaviors in Maternally Separated Rats Following Repeated Fasting/Refeeding Cycles

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Jeong Won Jahng ◽  
Sang Bae Yoo ◽  
Jin Young Kim ◽  
Bom-Taeck Kim ◽  
Jong-Ho Lee
Keyword(s):  
Dopaminergic Neurons ◽  
Eating Behaviors ◽  
Maternal Separation ◽  
Brain Dopamine ◽  
Ambulatory Activity ◽  
Dopaminergic Activity ◽  
Midbrain Dopaminergic Neurons ◽  
Underlying Mechanisms ◽  
Increased Activity ◽  
Pituitary Adrenal Axis

We have previously reported that rats that experienced 3 h of daily maternal separation during the first 2 weeks of birth (MS) showed binge-like eating behaviors with increased activity of the hypothalamic-pituitary-adrenal axis when they were subjected to fasting/refeeding cycles repeatedly. In this study, we have examined the psychoemotional behaviors of MS rats on the fasting/refeeding cycles, together with their brain dopamine levels. Fasting/refeeding cycles normalized the ambulatory activity of MS rats, which was decreased by MS experience. Depression-like behaviors, but not anxiety, by MS experience were improved after fasting/refeeding cycles. Fasting/refeeding cycles did not significantly affect the behavioral scores of nonhandled (NH) control rats. Fasting/refeeding cycles increased dopamine levels not only in the hippocampus but also in the midbrain dopaminergic neurons in MS rats, but not in NH controls. Results demonstrate that fasting/refeeding cycles increase the mesohippocampal dopaminergic activity and improve depression-like behaviors in rats that experienced MS. Together with our previous paper, it is suggested that increased dopamine neurotransmission in the hippocampus may be implicated in the underlying mechanisms by which the fasting/refeeding cycles induce binge-like eating and improve depression-like behaviors in MS rats.

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.

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 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 incentive circuit: memory dynamics in the mushroom body of Drosophila melanogaster

2021 ◽  
Author(s):  
Evripidis Gkanias ◽  
Li Yan McCurdy ◽  
Michael N Nitabach ◽  
Barbara Webb
Keyword(s):  
Drosophila Melanogaster ◽  
Mushroom Body ◽  
Learning Rule ◽  
Detailed Examination ◽  
Mushroom Bodies ◽  
Short Term ◽  
Output Neurons ◽  
Memory Acquisition ◽  
Exploration Exploitation

Insects adapt their response to stimuli, such as odours, according to their pairing with positive or negative reinforcements, such as sugar or shock. Recent electrophysiological and imaging findings in Drosophila melanogaster allow detailed examination of the neural mechanisms supporting acquisition, forgetting, and assimilation of memories. Drawing on this data, we identify a series of microcircuits within the mushroom bodies that reveal, for each motivational state, three different roles of dopaminergic and mushroom body output neurons in the memory dynamics. These microcircuits share components and form a unified system for rapid memory acquisition, transfer from short-term to long-term, and exploration/exploitation trade-off. We show that combined with a novel biologically plausible learning rule, a computational model of the full circuit reproduces the observed changes in the activity of each of these neurons in conditioning paradigms and can be used for flexible behavioural control.

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.

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