Specific Dopaminergic Neurons for the Formation of Labile Aversive Memory

Aso, Yoshinori; Siwanowicz, Igor; Bräcker, Lasse B.; Ito, Kei; Kitamoto, Toshihiro; Tanimoto, Hiromu

doi:10.1016/j.cub.2010.06.048

Cited by 274 publications

(394 citation statements)

References 52 publications

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“…Functionally, both types of neurons are responsive to multiple odors and show enhanced neural activity to conditioned odor after repetitive training. During olfactory conditioning, an odor CS signal is encoded in sparse subsets of MB neurons (31), whereas the aversive US signal is delivered to most, if not all, Kenyon cells via dopaminergic neurons (29,32,33). The striking dendritic plasticity observed after antennal removal (Fig.…”

Section: Discussionmentioning

confidence: 99%

Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation

Pai

Chen

Lin

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

116

135

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Memory is initially labile and gradually consolidated over time through new protein synthesis into a long-lasting stable form. Studies of odor-shock associative learning in Drosophila have established the mushroom body (MB) as a key brain structure involved in olfactory long-term memory (LTM) formation. Exactly how early neural activity encoded in thousands of MB neurons is consolidated into protein-synthesis-dependent LTM remains unclear. Here, several independent lines of evidence indicate that changes in two MB vertical lobe V3 (MB-V3) extrinsic neurons are required and contribute to an extended neural network involved in olfactory LTM: (i) inhibiting protein synthesis in MB-V3 neurons impairs LTM; (ii) MB-V3 neurons show enhanced neural activity after spaced but not massed training; (iii) MB-V3 dendrites, synapsing with hundreds of MB α/β neurons, exhibit dramatic structural plasticity after removal of olfactory inputs; (iv) neurotransmission from MB-V3 neurons is necessary for LTM retrieval; and (v) RNAi-mediated downregulation of oo18 RNA-binding protein (involved in local regulation of protein translation) in MB-V3 neurons impairs LTM. Our results suggest a model of long-term memory formation that includes a systems-level consolidation process, wherein an early, labile olfactory memory represented by neural activity in a sparse subset of MB neurons is converted into a stable LTM through protein synthesis in dendrites of MB-V3 neurons synapsed onto MB α lobes.L ong-term memory (LTM) and long-term synaptic plasticity require de novo protein synthesis, which is regulated at transcriptional and/or translational levels in a synapse-specific manner (1-3). Synapse-specific plasticity during LTM formation in some contexts may involve local regulation of protein translation by a family of RNA-binding proteins, the cytoplasmic polyadenylation element-binding proteins (CPEBs) (2). Neuronal CPEBs have two conformational states. The inactive state predominates at low levels of CPEB expression and represses translation from nascent mRNAs. The active state is achieved either via a self-perpetuating prion-like state when expression levels surpass a threshold or via Ca 2+ /calmoduline-dependent protein kinase II (CaMKII)-mediated phosphorylation, and translation is initiated by elongation of an mRNA's poly-A tail (4-6). In other species, CPEB1 has been shown to contribute to long-term facilitation or potentiation (5, 7). In Drosophila, oo18 RNA-binding protein 2 (ORB2) appears required for long-term memory formation after courtship conditioning (8, 9). Any role for ORB in fruit fly memory formation, however, remains unclear.Drosophila can learn to associate an odor (conditioned stimulus, CS) with foot-shock punishment (unconditioned stimulus, US). This odor-shock association initially is labile, lasting for only about a day after one training session. With repetitive, spaced training (ST) sessions (rest intervals between each session), a protein synthesis-dependent, LTM is formed. With repetitive, massed training (MT) ses...

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Section: Discussionmentioning

confidence: 99%

Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation

Pai

Chen

Lin

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

116

135

View full text Add to dashboard Cite

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“…They lack therefore MBs capable of integrating information across sensory modalities and allowing the extraction of sensory-independent regularities as those underlying concepts. Despite their tight association with elemental forms of memory [16,17,73 -75], reinforcement systems [69,71,76] and attention-like processes [63,64], the fly MBs lack the multi-sensoriality that would be required to encode conceptual rules that are valid across distinct sensory modalities. Admittedly, concepts could be established within a single modality.…”

Section: Neurobiological Insights Into Conceptual Learning In Beesmentioning

confidence: 99%

Conceptual learning by miniature brains

2013

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Concepts act as a cornerstone of human cognition. Humans and non-human primates learn conceptual relationships such as 'same', 'different', 'larger than', 'better than', among others. In all cases, the relationships have to be encoded by the brain independently of the physical nature of objects linked by the relation. Consequently, concepts are associated with high levels of cognitive sophistication and are not expected in an insect brain. Yet, various works have shown that the miniature brain of honeybees rapidly learns conceptual relationships involving visual stimuli. Concepts such as 'same', 'different', 'above/below of' or 'left/right are well mastered by bees. We review here evidence about concept learning in honeybees and discuss both its potential adaptive advantage and its possible neural substrates. The results reviewed here challenge the traditional view attributing supremacy to larger brains when it comes to the elaboration of concepts and have wide implications for understanding how brains can form conceptual relations.

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“…Dopaminergic neurons are believed to convey the reinforcement signal from foot shock (19,24). Accordingly, mutants of the D1 dopamine receptor (dDA1), dumb 1 and dumb 2 , show no learning of simultaneous conditioning (40).…”

Section: Inhibition Of Rac-mediated Forgetting Enhances Trace Conditimentioning

confidence: 99%

“…In a simplified molecular model, the CS + and US converge on Rutabaga adenylyl cyclase (Rut-AC), which in turn triggers the cAMP/PKA signaling cascade that drives synaptic plasticity and learned behavior (20)(21)(22). The neural circuits processing the CS and US information are now being studied at single-cell resolution (e.g., 19,23,24) and an increasing repertoire of learning/memory-related molecules are being identified (e.g., 25,26). The abundant knowledge of this conditioned behavior makes the fruit fly an attractive model to study trace conditioning (14,27,28).…”

mentioning

confidence: 99%

Distinct molecular underpinnings of Drosophila olfactory trace conditioning

Shuai

Qin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Trace conditioning is valued as a simple experimental model to assess how the brain associates events that are discrete in time. Here, we adapted an olfactory trace conditioning procedure in Drosophila melanogaster by training fruit flies to avoid an odor that is followed by foot shock many seconds later. The molecular underpinnings of the learning are distinct from the well-characterized simultaneous conditioning, where odor and punishment temporally overlap. First, Rutabaga adenylyl cyclase (Rut-AC), a putative molecular coincidence detector vital for simultaneous conditioning, is dispensable in trace conditioning. Second, dominant-negative Rac expression, thought to sustain early labile memory, significantly enhances learning of trace conditioning, but leaves simultaneous conditioning unaffected. We further show that targeting Rac inhibition to the mushroom body (MB) but not the antennal lobe (AL) suffices to achieve the enhancement effect. Moreover, the absence of trace conditioning learning in D1 dopamine receptor mutants is rescued by restoration of expression specifically in the adult MB. These results suggest the MB as a crucial neuroanatomical locus for trace conditioning, which may harbor a Rac activity-sensitive olfactory "sensory buffer" that later converges with the punishment signal carried by dopamine signaling. The distinct molecular signature of trace conditioning revealed here shall contribute to the understanding of how the brain overcomes a temporal gap in potentially related events.learning and memory | olfaction | cAMP | Rho GTPase I n trace conditioning, the conditional stimulus (CS) and the unconditional stimulus (US) are separated in time by a stimulus-free interval (1). This so-called "trace interval" can last for a fraction of a second in eyeblink conditioning but many seconds in fear conditioning, which poses a challenging question: how does the brain overcome this temporal gap to form the association between the CS and US (2)? Intriguingly, trace conditioning in mammals engages neural substrates fundamentally different from delay conditioning, where the CS precedes but also temporally overlaps with the US (3). Early evidence comes from lesion studies with experimental animals showing that acquisition of trace conditioning requires intact hippocampal formation (4, 5) and medial prefrontal cortex (6), whereas delay conditioning can occur even with the entire forebrain removed (7,8). Later studies involving human subjects further validate the involvement of different brain circuits in these two conditioning variants and even suggest, more surprisingly, that conscious awareness might be a prerequisite for trace but not delay conditioning (9, 10). It is then hypothesized that the participation of hippocampus and neocortex, as well as the associated higher cognitive function, is necessary in trace conditioning to maintain a representation of the CS or CS/US contingency so as to bridge the temporal gap (11, 12). However, little is known about what form this representation takes and how it e...

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Specific Dopaminergic Neurons for the Formation of Labile Aversive Memory

Cited by 274 publications

References 52 publications

Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation

Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation

Conceptual learning by miniature brains

Distinct molecular underpinnings of Drosophila olfactory trace conditioning

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