Trace Conditioning in Drosophila Induces Associative Plasticity in Mushroom Body Kenyon Cells and Dopaminergic 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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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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Differential Conditioning Produces Merged Long-term Memory in Drosophila

10.1101/2021.01.13.426486 ◽

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

eLife ◽

10.7554/elife.35264 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 49

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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Differential conditioning produces merged long-term memory in Drosophila

eLife ◽

10.7554/elife.66499 ◽

2021 ◽

Vol 10 ◽

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

Multiple spaced trials of aversive differential conditioning can produce two independent long-term 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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Reward signaling in a recurrent circuit of dopaminergic neurons and Kenyon cells

10.1101/357145 ◽

2018 ◽

Author(s):

Radostina Lyutova ◽

Maximilian Pfeuffer ◽

Dennis Segebarth ◽

Jens Habenstein ◽

Mareike Selcho ◽

...

Keyword(s):

Learning And Memory ◽

Dopaminergic Neurons ◽

Mushroom Body ◽

Olfactory Learning ◽

Mushroom Bodies ◽

Neuronal Circuitry ◽

Sustained Activity ◽

Kenyon Cells ◽

Reward Information ◽

The Brain

1.AbstractDopaminergic neurons in the brain of theDrosophilalarva play a key role in mediating reward information to the mushroom bodies during appetitive olfactory learning and memory. Using optogenetic activation of Kenyon cells we provide evidence that a functional recurrent signaling loop exists between Kenyon cells and dopaminergic neurons of the primary protocerebral anterior (pPAM) cluster. An optogenetic activation of Kenyon cells paired with an odor is sufficient to induce appetitive memory, while a simultaneous impairment of the dopaminergic pPAM neurons abolishes memory expression. Thus, dopaminergic pPAM neurons mediate reward information to the Kenyon cells, but in turn receive feedback from Kenyon cells. We further show that the activation of recurrent signaling routes within mushroom body circuitry increases the persistence of an odor-sugar memory. Our results suggest that sustained activity in a neuronal circuitry is a conserved mechanism in insects and vertebrates to consolidate memories.

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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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Taurine-, aspartate- and glutamate-like immunoreactivity identifies chemically distinct subdivisions of Kenyon cells in the cockroach mushroom body

The Journal of Comparative Neurology ◽

10.1002/cne.1355 ◽

2001 ◽

Vol 439 (3) ◽

pp. 352-367 ◽

Cited By ~ 54

Author(s):

Irina Sinakevitch ◽

Sarah M. Farris ◽

Nicholas J. Strausfeld

Keyword(s):

Mushroom Body ◽

Kenyon Cells

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I A in Kenyon Cells of the Mushroom Body of Honeybees Resembles Shaker Currents: Kinetics, Modulation by K+, and Simulation

Journal of Neurophysiology ◽

10.1152/jn.1999.81.4.1749 ◽

1999 ◽

Vol 81 (4) ◽

pp. 1749-1759 ◽

Cited By ~ 24

Author(s):

Corinna Pelz ◽

Johannes Jander ◽

Hendrik Rosenboom ◽

Martin Hammer ◽

Randolf Menzel

Keyword(s):

Action Potential ◽

Time Constant ◽

Mushroom Body ◽

Delayed Rectifier ◽

Patch Clamp Technique ◽

Time Constants ◽

Voltage Gated ◽

Kenyon Cells ◽

Recovery From Inactivation ◽

A Current

I A in Kenyon cells of the mushroom body of honeybees resembles shaker currents: kinetics, modulation by K+, and simulation. Cultured Kenyon cells from the mushroom body of the honeybee, Apis mellifera, show a voltage-gated, fast transient K+ current that is sensitive to 4-aminopyridine, an A current. The kinetic properties of this A current and its modulation by extracellular K+ ions were investigated in vitro with the whole cell patch-clamp technique. The A current was isolated from other voltage-gated currents either pharmacologically or with suitable voltage-clamp protocols. Hodgkin- and Huxley-style mathematical equations were used for the description of this current and for the simulation of action potentials in a Kenyon cell model. Activation and inactivation of the A current are fast and voltage dependent with time constants of 0.4 ± 0.1 ms (means ± SE) at +45 mV and 3.0 ± 1.6 ms at +45 mV, respectively. The pronounced voltage dependence of the inactivation kinetics indicates that at least a part of this current of the honeybee Kenyon cells is a shaker-like current. Deactivation and recovery from inactivation also show voltage dependency. The time constant of deactivation has a value of 0.4 ± 0.1 ms at −75 mV. Recovery from inactivation needs a double-exponential function to be fitted adequately; the resulting time constants are 18 ± 3.1 ms for the fast and 745 ± 107 ms for the slow process at −75 mV. Half-maximal activation of the A current occurs at −0.7 ± 2.9 mV, and half-maximal inactivation occurs at −54.7 ± 2.4 mV. An increase in the extracellular K+concentration increases the conductance and accelerates the recovery from inactivation of the A current, affecting the slow but not the fast time constant. With respect to these modulations the current under investigation resembles some of the shaker-like currents. The data of the A current were incorporated into a reduced computational model of the voltage-gated currents of Kenyon cells. In addition, the model contained a delayed rectifier K+ current, a Na+current, and a leakage current. The model is able to generate an action potential on current injection. The model predicts that the A current causes repolarization of the action potential but not a delay in the initiation of the action potential. It further predicts that the activation of the delayed rectifier K+ current is too slow to contribute markedly to repolarization during a single action potential. Because of its fast activation, the A current reduces the amplitude of the net depolarizing current and thus reduces the peak amplitude and the duration of the action potential.

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Current- and Voltage-Clamp Recordings and Computer Simulations of Kenyon Cells in the Honeybee

Journal of Neurophysiology ◽

10.1152/jn.01259.2003 ◽

2004 ◽

Vol 92 (4) ◽

pp. 2589-2603 ◽

Cited By ~ 43

Author(s):

Daniel G. Wüstenberg ◽

Milena Boytcheva ◽

Bernd Grünewald ◽

John H. Byrne ◽

Randolf Menzel ◽

...

Keyword(s):

Voltage Clamp ◽

Mushroom Body ◽

Outward Current ◽

Delayed Rectifier ◽

Transient Outward Current ◽

Insect Brain ◽

Type Model ◽

Kenyon Cells ◽

Fast Transient

The mushroom body of the insect brain is an important locus for olfactory information processing and associative learning. The present study investigated the biophysical properties of Kenyon cells, which form the mushroom body. Current- and voltage-clamp analyses were performed on cultured Kenyon cells from honeybees. Current-clamp analyses indicated that Kenyon cells did not spike spontaneously in vitro. However, spikes could be elicited by current injection in approximately 85% of the cells. Of the cells that produced spikes during a 1-s depolarizing current pulse, approximately 60% exhibited repetitive spiking, whereas the remaining approximately 40% fired a single spike. Cells that spiked repetitively showed little frequency adaptation. However, spikes consistently became broader and smaller during repetitive activity. Voltage-clamp analyses characterized a fast transient Na+ current ( INa), a delayed rectifier K+ current ( IK,V), and a fast transient K+ current ( IK,A). Using the neurosimulator SNNAP, a Hodgkin–Huxley-type model was developed and used to investigate the roles of the different currents during spiking. The model led to the prediction of a slow transient outward current ( IK,ST) that was subsequently identified by reevaluating the voltage-clamp data. Simulations indicated that the primary currents that underlie spiking are INa and IK,V, whereas IK,A and IK,ST primarily determined the responsiveness of the model to stimuli such as constant or oscillatory injections of current.

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