Animals employ diverse learning rules and synaptic plasticity dynamics to record temporal and statistical information about the world. However, the molecular mechanisms underlying this diversity are poorly understood. The anatomically defined compartments of the insect mushroom body function as parallel units of associative learning, with different learning rates, memory decay dynamics and flexibility (Aso and Rubin, 2016). Here, we show that nitric oxide (NO) acts as a neurotransmitter in a subset of dopaminergic neurons in Drosophila. NO’s effects develop more slowly than those of dopamine and depend on soluble guanylate cyclase in postsynaptic Kenyon cells. NO acts antagonistically to dopamine; it shortens memory retention and facilitates the rapid updating of memories. The interplay of NO and dopamine enables memories stored in local domains along Kenyon cell axons to be specialized for predicting the value of odors based only on recent events. Our results provide key mechanistic insights into how diverse memory dynamics are established in parallel memory systems.
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Neural circuit mechanisms for transforming learned olfactory valences into wind-oriented movement
How memories are used by the brain to guide future action is poorly understood. In olfactory associative learning in
- Award ID(s):
- 2034783
- NSF-PAR ID:
- 10494753
- Publisher / Repository:
- eLife Sciences Publications
- Date Published:
- Journal Name:
- eLife
- Volume:
- 12
- ISSN:
- 2050-084X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Sleep is a fundamental behavioral state important for survival and is universal in animals with sufficiently complex nervous systems. As a highly conserved neurobehavioral state, sleep has been described in species ranging from jellyfish to humans. Biogenic amines like dopamine, serotonin and norepinephrine have been shown to be critical for sleep regulation across species but the precise circuit mechanisms underlying how amines control persistence of sleep, arousal and wakefulness remain unclear. The fruit fly,
Drosophila melanogaster , provides a powerful model system for the study of sleep and circuit mechanisms underlying state transitions and persistence of states to meet the organisms motivational and cognitive needs. InDrosophila , two neuropils in the central brain, the mushroom body (MB) and the central complex (CX) have been shown to influence sleep homeostasis and receive aminergic neuromodulator input critical to sleep–wake switch. Dopamine neurons (DANs) are prevalent neuromodulator inputs to the MB but the mechanisms by which they interact with and regulate sleep- and wake-promoting neurons within MB are unknown. Here we investigate the role of subsets of PAM-DANs that signal wakefulness and project to wake-promoting compartments of the MB. We find that PAM-DANs are GABA responsive and require GABAA-Rdl receptor in regulating sleep. In mapping the pathways downstream of PAM neurons innervating γ5 and β′2 MB compartments we find that wakefulness is regulated by both DopR1 and DopR2 receptors in downstream Kenyon cells (KCs) and mushroom body output neurons (MBONs). Taken together, we have identified and characterized a dopamine modulated sleep microcircuit within the mushroom body that has previously been shown to convey information about positive and negative valence critical for memory formation. These studies will pave way for understanding how flies balance sleep, wakefulness and arousal. -
Morrison, Abigail (Ed.)The Drosophila mushroom body exhibits dopamine dependent synaptic plasticity that underlies the acquisition of associative memories. Recordings of dopamine neurons in this system have identified signals related to external reinforcement such as reward and punishment. However, other factors including locomotion, novelty, reward expectation, and internal state have also recently been shown to modulate dopamine neurons. This heterogeneity is at odds with typical modeling approaches in which these neurons are assumed to encode a global, scalar error signal. How is dopamine dependent plasticity coordinated in the presence of such heterogeneity? We develop a modeling approach that infers a pattern of dopamine activity sufficient to solve defined behavioral tasks, given architectural constraints informed by knowledge of mushroom body circuitry. Model dopamine neurons exhibit diverse tuning to task parameters while nonetheless producing coherent learned behaviors. Notably, reward prediction error emerges as a mode of population activity distributed across these neurons. Our results provide a mechanistic framework that accounts for the heterogeneity of dopamine activity during learning and behavior.more » « less
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Dopaminergic neurons with distinct projection patterns and physiological properties compose memory subsystems in a brain. However, it is poorly understood whether or how they interact during complex learning. Here, we identify a feedforward circuit formed between dopamine subsystems and show that it is essential for second-order conditioning, an ethologically important form of higher-order associative learning. The Drosophila mushroom body comprises a series of dopaminergic compartments, each of which exhibits distinct memory dynamics. We find that a slow and stable memory compartment can serve as an effective ‘teacher’ by instructing other faster and transient memory compartments via a single key interneuron, which we identify by connectome analysis and neurotransmitter prediction. This excitatory interneuron acquires enhanced response to reward-predicting odor after first-order conditioning and, upon activation, evokes dopamine release in the ‘student’ compartments. These hierarchical connections between dopamine subsystems explain distinct properties of first- and second-order memory long known by behavioral psychologists.more » « less
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Abstract Olfactory projection neurons convey information from the insect antennal lobe (AL) to higher brain centers. Previous reports have demonstrated that pheromone‐responsive projection neurons with cell bodies in the moth medial cell cluster (
mc PNs) predominantly have dendritic arborizations in the sexually dimorphic macroglomerular complex (MGC) and send an axon from the AL to the calyces of the mushroom body (CA) as well as the lateral horn (LH) of the protocerebrum via the medial AL tract. These neurons typically exhibit a narrow odor tuning range related to the restriction of their dendritic arbors within a single glomerulus (uniglomerular). In this study, we report on the diverse physiological and morphological properties of a group of pheromone‐responsive olfactory projection neurons with cell bodies in the AL lateral cell cluster (MGClc PNs) of two closely related moth species. All pheromone‐responsivelc PNs appeared to exhibit “basket‐like” dendritic arborizations in two MGC compartments and made connections with various protocerebral targets including ventrolateral and superior neuropils via projections primarily through the lateral AL tract and to a lesser extent the mediolateral antennal lobe tract. Physiological characterization of MGClc PNs also revealed a diversity of response profiles including those either enhanced by or reliant upon presentation of a pheromone blend. These responses manifested themselves as higher maximum firing rates and/or improved temporal resolution of pulsatile stimuli. MGClc PNs therefore participate in conveying diverse olfactory information relating to qualitative and temporal facets of the pheromone stimulus to a more expansive number of protocerebral targets than theirmc PN counterparts.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.7554/eLife.85756
