scholarly journals Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory

2015 ◽  
Vol 112 (48) ◽  
pp. E6663-E6672 ◽  
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.

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

2019 ◽  
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.

scholarly journals Persistent activity in a recurrent circuit underlies courtship memory in Drosophila

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Xiaoliang Zhao ◽  
Daniela Lenek ◽  
Ugur Dag ◽  
Barry J Dickson ◽  
Krystyna Keleman
Keyword(s):  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Neural Circuits ◽  
Short Term Memory ◽  
Persistent Activity ◽  
Short Term ◽  
Present Evidence ◽  
Term Memory ◽  
Time Periods ◽  
Over Time

Recurrent connections are thought to be a common feature of the neural circuits that encode memories, but how memories are laid down in such circuits is not fully understood. Here we present evidence that courtship memory in Drosophila relies on the recurrent circuit between mushroom body gamma (MBγ), M6 output, and aSP13 dopaminergic neurons. We demonstrate persistent neuronal activity of aSP13 neurons and show that it transiently potentiates synaptic transmission from MBγ>M6 neurons. M6 neurons in turn provide input to aSP13 neurons, prolonging potentiation of MBγ>M6 synapses over time periods that match short-term memory. These data support a model in which persistent aSP13 activity within a recurrent circuit lays the foundation for a short-term memory.

scholarly journals Olfactory Learning in Drosophila

Physiology ◽  
2010 ◽  
Vol 25 (6) ◽  
pp. 338-346 ◽  
Author(s):  
Germain U. Busto ◽  
Isaac Cervantes-Sandoval ◽  
Ronald L. Davis
Keyword(s):  
Dopaminergic Neurons ◽  
Mushroom Body ◽  
Sensory Information ◽  
Brain Regions ◽  
Olfactory Learning ◽  
Mushroom Bodies ◽  
Neural Pathways ◽  
Olfactory Information ◽  
Appetitive Stimuli ◽  
The Brain

Studies of olfactory learning in Drosophila have provided key insights into the brain mechanisms underlying learning and memory. One type of olfactory learning, olfactory classical conditioning, consists of learning the contingency between an odor with an aversive or appetitive stimulus. This conditioning requires the activity of molecules that can integrate the two types of sensory information, the odorant as the conditioned stimulus and the aversive or appetitive stimulus as the unconditioned stimulus, in brain regions where the neural pathways for the two stimuli intersect. Compelling data indicate that a particular form of adenylyl cyclase functions as a molecular integrator of the sensory information in the mushroom body neurons. The neuronal pathway carrying the olfactory information from the antennal lobes to the mushroom body is well described. Accumulating data now show that some dopaminergic neurons provide information about aversive stimuli and octopaminergic neurons about appetitive stimuli to the mushroom body neurons. Inhibitory inputs from the GABAergic system appear to gate olfactory information to the mushroom bodies and thus control the ability to learn about odors. Emerging data obtained by functional imaging procedures indicate that distinct memory traces form in different brain regions and correlate with different phases of memory. The results from these and other experiments also indicate that cross talk between mushroom bodies and several other brain regions is critical for memory formation.

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 Strain- and age-dependent features of the nigro-striatal circuit in three common laboratory mouse strains, C57BL/6J, A/J, and DBA/2J - Implications for Parkinson’s disease modeling

2020 ◽  
Author(s):  
Mélanie H. Thomas ◽  
Mona Karout ◽  
Beatriz Pardo Rodriguez ◽  
Yujuan Gui ◽  
Christian Jaeger ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Brain ◽  
Dopaminergic Neurons ◽  
Mouse Strains ◽  
List Type ◽  
Background Strain ◽  
Age Related ◽  
Health And Disease ◽  
Over Time

AbstractMouse models have been instrumental in understanding genetic determinants of aging and its crucial role in neurodegenerative diseases. However, few studies have analyzed the evolution of the mouse brain over time at baseline. Furthermore, mouse brain studies are commonly conducted on the C57BL/6 strain, limiting the analysis to a specific genetic background. In Parkinson’s disease, the gradual demise of nigral dopaminergic neurons mainly contributes to the motor symptoms. Interestingly, a decline of the dopaminergic neuron function and integrity is also a characteristic of physiological aging in some species. Age-related nigro-striatal features have never been studied in mice of different genetic backgrounds. In this study, we analyze the morphological features in the striatum of three common mouse strains, C57BL/6J, A/J, and DBA/2J at 3-, 9- and 15 months of age. By measuring dopaminergic markers, we uncover age-related changes that differ between strains and evolve dynamically over time. Overall, our results highlight the importance of considering background strain and age when studying the murine nigro-striatal circuit in health and disease.HighlightsStudy of the integrity of the nigro-striatal circuit in C57BL/6J, A/J, and DBA/2J at different agesAge related evolution of essential features of nigral dopaminergic neurons differ between strainsConsider background strain and age is crutial to study the nigrostriatal circuit in health and disease

TER94 , the Drosophila Homologue of the ALS-related VCP gene, Influences Lifespan and Leads to a Decline in Motor Function

2020 ◽  
Author(s):  
Emily Priscilla Hurley ◽  
Brian Ernest Staveley
Keyword(s):  
Neurodegenerative Disease ◽  
Motor Neurons ◽  
Dopaminergic Neurons ◽  
Altered Expression ◽  
Locomotor Function ◽  
Aaa Atpase ◽  
Median Lifespan ◽  
Novel Model ◽  
Locomotor Ability ◽  
Over Time

Abstract Background: Valosin-Containing Protein (VCP) is an essential AAA+ ATPase with diverse functions within the cell. Mutations in the VCP gene have been detected in patients with familial amyotrophic lateral sclerosis (ALS). The aim of this study is to create a novel model of human neurodegenerative disease in Drosophila melanogaster by altering the expression of TER94, the Drosophila orthologue of the human VCP gene. TER94 expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time. Altered TER94 expression in combination with the altered expression of known Parkinson Disease (PD) genes was examined to investigate potential interactions.Results: Inhibition of TER94 altered median lifespan in a manner dependent upon the transgene selected for use and the tissue-specific expression directed by the Gal4 transgene selected. Locomotor ability was significantly reduced in all cases of TER94 inhibition tested. The inhibition of TER94 by two TER94-RNAi inhibitory transgenes, in the motor neurons via D42-Gal4 lead to increases in median lifespan, with one inhibitory transgene generating a slightly reduced lifespan. Inhibition of TER94 in the dopaminergic neurons resulted in a severe reduction in lifespan. The co-inhibition of TER94 and parkin in the neurons resulted in a major decline in lifespan by approximately 30%. While the inhibition of TER94 and the co-expression of alpha-synuclein in the neurons resulted in an increase in lifespan by approximately 28%. Conclusions: The inhibition of TER94 in the motor neurons is an interesting model of ALS, due to the small, but reduced lifespan coupled with a strong decline in locomotor function. The inhibition of TER94 in the dopaminergic neurons is a potential model of ALS, due to the reduction of both lifespan and locomotor function over time. The co-inhibition of TER94 and parkin in the neurons provides a promising novel model of neurodegenerative disease, displaying a great reduction in lifespan and in locomotor ability over time.

scholarly journals Prolonged exposure to stressors suppresses exploratory behavior in zebrafish larvae

2020 ◽  
Vol 223 (22) ◽  
pp. jeb224964
Author(s):  
William A. Haney ◽  
Bushra Moussaoui ◽  
James A. Strother
Keyword(s):  
Dopaminergic Neurons ◽  
Prolonged Exposure ◽  
Area Postrema ◽  
Model Organism ◽  
Neural Correlates ◽  
Neural Pathways ◽  
Zebrafish Larvae ◽  
Induced Changes ◽  
Acute Stressor ◽  
Light Preference

ABSTRACTEnvironmental stressors induce rapid physiological and behavioral shifts in vertebrate animals. However, the neurobiological mechanisms responsible for stress-induced changes in behavior are complex and not well understood. Similar to mammalian vertebrates, zebrafish adults display a preference for dark environments that is associated with predator avoidance, enhanced by stressors, and broadly used in assays for anxiety-like behavior. Although the larvae of zebrafish are a prominent model organism for understanding neural circuits, few studies have examined the effects of stressors on their behavior. This study examines the effects of noxious chemical and electric shock stressors on locomotion and light preference in zebrafish larvae. We found that both stressors elicited similar changes in behavior. Acute exposure induced increased swimming activity, while prolonged exposure depressed activity. Neither stressor produced a consistent shift in light–dark preference, but prolonged exposure to these stressors resulted in a pronounced decrease in exploration of different visual environments. We also examined the effects of exposure to a noxious chemical cue using whole-brain calcium imaging, and identified neural correlates in the area postrema, an area of the hindbrain containing noradrenergic and dopaminergic neurons. Pharmaceutical blockade experiments showed that α-adrenergic receptors contribute to the behavioral response to an acute stressor but are not necessary for the response to a prolonged stressor. These results indicate that zebrafish larvae have complex behavioral responses to stressors comparable to those of adult animals, and also suggest that these responses are mediated by similar neural pathways.

scholarly journals ADHD-like behaviors caused by inactivation of a transcription factor controlling the balance of inhibitory and excitatory neuron development in the mouse anterior brainstem

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Francesca Morello ◽  
Vootele Voikar ◽  
Pihla Parkkinen ◽  
Anne Panhelainen ◽  
Marko Rosenholm ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dopaminergic Neurons ◽  
Dopaminergic System ◽  
Developmental Pathways ◽  
Neuron Development ◽  
Learning Deficits ◽  
Glutamatergic Neurons ◽  
Midbrain Dopaminergic Neurons ◽  
Dopamine Signaling ◽  
Neurochemical Changes

Abstract The neural circuits regulating motivation and movement include midbrain dopaminergic neurons and associated inhibitory GABAergic and excitatory glutamatergic neurons in the anterior brainstem. Differentiation of specific subtypes of GABAergic and glutamatergic neurons in the mouse embryonic brainstem is controlled by a transcription factor Tal1. This study characterizes the behavioral and neurochemical changes caused by the absence of Tal1 function. The Tal1cko mutant mice are hyperactive, impulsive, hypersensitive to reward, have learning deficits and a habituation defect in a novel environment. Only minor changes in their dopaminergic system were detected. Amphetamine induced striatal dopamine release and amphetamine induced place preference were normal in Tal1cko mice. Increased dopamine signaling failed to stimulate the locomotor activity of the Tal1cko mice, but instead alleviated their hyperactivity. Altogether, the Tal1cko mice recapitulate many features of the attention and hyperactivity disorders, suggesting a role for Tal1 regulated developmental pathways and neural structures in the control of motivation and movement.

scholarly journals Pedunculopontine glutamatergic neurons control spike patterning in substantia nigra dopaminergic neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Daniel J Galtieri ◽  
Chad M Estep ◽  
David L Wokosin ◽  
Stephen Traynelis ◽  
D James Surmeier
Keyword(s):  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Glutamatergic Synapses ◽  
Glutamatergic Neurons ◽  
Oscillatory Mechanisms ◽  
Goal Directed Behavior ◽  
Stimulation Of

Burst spiking in substantia nigra pars compacta (SNc) dopaminergic neurons is a key signaling event in the circuitry controlling goal-directed behavior. It is widely believed that this spiking mode depends upon an interaction between synaptic activation of N-methyl-D-aspartate receptors (NMDARs) and intrinsic oscillatory mechanisms. However, the role of specific neural networks in burst generation has not been defined. To begin filling this gap, SNc glutamatergic synapses arising from pedunculopotine nucleus (PPN) neurons were characterized using optical and electrophysiological approaches. These synapses were localized exclusively on the soma and proximal dendrites, placing them in a good location to influence spike generation. Indeed, optogenetic stimulation of PPN axons reliably evoked spiking in SNc dopaminergic neurons. Moreover, burst stimulation of PPN axons was faithfully followed, even in the presence of NMDAR antagonists. Thus, PPN-evoked burst spiking of SNc dopaminergic neurons in vivo may not only be extrinsically triggered, but extrinsically patterned as well.

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