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

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.

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Valence and state-dependent population coding in dopaminergic neurons in the fly mushroom body

10.1101/809277 ◽

2019 ◽

Author(s):

K.P. Siju ◽

Vilim Stih ◽

Sophie Aimon ◽

Julijana Gjorgjieva ◽

Ruben Portugues ◽

...

Keyword(s):

Dopaminergic Neurons ◽

Mushroom Body ◽

Physiological State ◽

Relevant Information ◽

Population Coding ◽

Behavioral State ◽

Population Activity ◽

Registration Method ◽

Sensory Stimuli

SummaryNeuromodulation permits flexibility of synapses, neural circuits and ultimately behavior. One neuromodulator, dopamine, has been studied extensively in its role as reward signal during learning and memory across animal species. Newer evidence suggests that dopaminergic neurons (DANs) can modulate sensory perception acutely, thereby allowing an animal to adapt its behavior and decision-making to its internal and behavioral state. In addition, some data indicate that DANs are heterogeneous and convey different types of information as a population. We have investigated DAN population activity and how it could encode relevant information about sensory stimuli and state by taking advantage of the confined anatomy of DANs innervating the mushroom body (MB) of the fly Drosophila melanogaster. Using in vivo calcium imaging and a custom 3D image registration method, we find that the activity of the population of MB DANs is predictive of the innate valence of an odor as well as the metabolic and mating state of the animal. Furthermore, DAN population activity is strongly correlated with walking or running, consistent with a role of dopamine in conveying behavioral state to the MB. Together our data and analysis suggest that distinct DAN population activities encode innate odor valence, movement and physiological state in a MB-compartment specific manner. We propose that dopamine shapes innate odor perception through combinatorial population coding of sensory valence, physiological and behavioral context.

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Predictive olfactory learning in Drosophila

Scientific Reports ◽

10.1038/s41598-021-85841-y ◽

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.

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Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1512792112 ◽

2015 ◽

Vol 112 (48) ◽

pp. E6663-E6672 ◽

Cited By ~ 31

Author(s):

Yichun Shuai ◽

Areekul Hirokawa ◽

Yulian Ai ◽

Min Zhang ◽

Wanhe Li ◽

...

Keyword(s):

Reversal Learning ◽

Dopaminergic Neurons ◽

Mushroom Body ◽

Biologically Active ◽

Molecular Pathways ◽

Neural Pathways ◽

Active Process ◽

Glutamatergic Neurons ◽

Memory Decay ◽

Over Time

Recent studies have identified molecular pathways driving forgetting and supported the notion that forgetting is a biologically active process. The circuit mechanisms of forgetting, however, remain largely unknown. Here we report two sets of Drosophila neurons that account for the rapid forgetting of early olfactory aversive memory. We show that inactivating these neurons inhibits memory decay without altering learning, whereas activating them promotes forgetting. These neurons, including a cluster of dopaminergic neurons (PAM-β′1) and a pair of glutamatergic neurons (MBON-γ4>γ1γ2), terminate in distinct subdomains in the mushroom body and represent parallel neural pathways for regulating forgetting. Interestingly, although activity of these neurons is required for memory decay over time, they are not required for acute forgetting during reversal learning. Our results thus not only establish the presence of multiple neural pathways for forgetting in Drosophila but also suggest the existence of diverse circuit mechanisms of forgetting in different contexts.

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Trace Conditioning in Drosophila Induces Associative Plasticity in Mushroom Body Kenyon Cells and Dopaminergic Neurons

Frontiers in Neural Circuits ◽

10.3389/fncir.2017.00042 ◽

2017 ◽

Vol 11 ◽

Cited By ~ 11

Author(s):

Kristina V. Dylla ◽

Georg Raiser ◽

C. Giovanni Galizia ◽

Paul Szyszka

Keyword(s):

Dopaminergic Neurons ◽

Mushroom Body ◽

Trace Conditioning ◽

Kenyon Cells

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Predictive olfactory learning in Drosophila

10.1101/2019.12.29.890533 ◽

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.

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

10.1101/2020.08.29.273276 ◽

2020 ◽

Cited By ~ 3

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.

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2023674118 ◽

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.

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State-Dependent Population Coding in Primary Auditory Cortex

Journal of Neuroscience ◽

10.1523/jneurosci.3318-14.2015 ◽

2015 ◽

Vol 35 (5) ◽

pp. 2058-2073 ◽

Cited By ~ 78

Author(s):

M. Pachitariu ◽

D. R. Lyamzin ◽

M. Sahani ◽

N. A. Lesica

Keyword(s):

Auditory Cortex ◽

Primary Auditory Cortex ◽

Population Coding ◽

State Dependent

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Spaced training forms complementary long-term memories of opposite valence inDrosophila

10.1101/785618 ◽

2019 ◽

Cited By ~ 2

Author(s):

Pedro F. Jacob ◽

Scott Waddell

Keyword(s):

Dopaminergic Neurons ◽

Mushroom Body ◽

Long Term Memory ◽

Odor Preference ◽

Additional Information ◽

Relative Safety ◽

Multiple Trials ◽

Over Time ◽

Odor Conditioning

AbstractForming long-term memory (LTM) in many cases requires repetitive experience spread over time. InDrosophila, aversive olfactory LTM is optimal following spaced training, multiple trials of differential odor conditioning with rest intervals. Studies often compare memory after spaced to that after massed training, same number of trials without interval. Here we show flies acquire additional information after spaced training, forming an aversive memory for the shock-paired odor and a ‘safety-memory’ for the explicitly unpaired odor. Safety-memory requires repetition, order and spacing of the training trials and relies on specific subsets of rewarding dopaminergic neurons. Co-existence of the aversive and safety memories can be measured as depression of odor-specific responses at different combinations of junctions in the mushroom body output network. Combining two particular outputs appears to signal relative safety. Learning a complementary safety memory thereby augments LTM performance after spaced training by making the odor preference more certain.

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