Forgetting Is Regulated via Musashi-Mediated Translational Control of the Arp2/3 Complex

Hadziselimovic, Nils; Vukojević, Vanja; Fábián, Péter; Milnik, Annette; Fastenrath, Matthias; Fenyves, Bánk G.; Hieber, Petra; Demougin, Philippe; Vogler, Christian; Quervain, Dominique J.‐F. de; Papassotiropoulos, Andreas; Steták, Attila

doi:10.1016/j.cell.2014.01.054

Cited by 87 publications

(114 citation statements)

References 47 publications

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“…phases of memory (H. P. Davis & Squire, 1984; Ghirardi, et al, 1995; Hawkins, et al, 2006; Jin et al, 2011; Michel et al, 2012; Parvez et al, 2005; Sutton et al, 2001) and for what is termed negative associative short-term memory in C. elegans that may actually be intermediate-term memory (Hadziselimovic et al, 2014). As in our previously published short-term associative memory assay, several thousand day 1 adult worms are starved for 1 hour, conditioned with food and 10% butanone for 1 hour, and then held on food before subsets of the trained population are tested for memory using a chemotaxis assay at specific time-points after training (Fig.…”

Section: Resultsmentioning

confidence: 99%

C. elegans positive olfactory associative memory is a molecularly conserved behavioral paradigm

Stein

Murphy

2014

Neurobiology of Learning and Memory

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While it is thought that short-term memory arises from changes in protein dynamics that increase the strength of synaptic signaling, many of the underlying fundamental molecular mechanisms remain unknown. Our lab developed a C. elegans assay of positive olfactory short-term associative memory (STAM), in which worms learn to associate food with an odor and can remember this association for over one hour. Here we use this massed olfactory associative assay to identify regulators of C. elegans short-term and intermediate-term associative memory (ITAM) processes. We show that there are unique molecular characteristics for different temporal phases of STAM, which include: learning, which is tested immediately after training, short-term memory, tested 30 minutes after training, intermediate-term memory, tested 1 hour after training, and forgetting, tested 2 hours after training. We find that, as in higher organisms, C. elegans STAM requires calcium and cAMP signaling, and ITAM requires protein translation. Additionally, we found that STAM and ITAM are distinct from olfactory adaptation, an associative paradigm in which worms learn to disregard an inherently attractive odor after starvation in the presence of that odor. Adaptation mutants show variable responses to short-term associative memory training. Our data distinguish between shorter forms of a positive associative memory in C. elegans that require canonical memory pathways. Study of STAM and ITAM in C. elegans could lead to a more general understanding of the distinctions between these important processes and also to the discovery of novel conserved memory regulators.

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Section: Resultsmentioning

confidence: 99%

C. elegans positive olfactory associative memory is a molecularly conserved behavioral paradigm

Stein

Murphy

2014

Neurobiology of Learning and Memory

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“…These two signaling systems appear to be tightly coupled and important for regulating spine structural plasticity (De Rubeis et al, 2013; Hadziselimovic et al, 2014). Further studies of the interplay between the local regulation of cytoskeleton and translation during spine structural plasticity will be provide us with a better understanding of these diseases as well as basic understanding of spine structural plasticity.…”

Section: Discussionmentioning

confidence: 99%

Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal Reorganization

Nakahata

Yasuda

2018

Front. Synaptic Neurosci.

183

161

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Dendritic spines are small protrusive structures on dendritic surfaces, and function as postsynaptic compartments for excitatory synapses. Plasticity of spine structure is associated with many forms of long-term neuronal plasticity, learning and memory. Inside these small dendritic compartments, biochemical states and protein-protein interactions are dynamically modulated by synaptic activity, leading to the regulation of protein synthesis and reorganization of cytoskeletal architecture. This in turn causes plasticity of structure and function of the spine. Technical advances in monitoring molecular behaviors in single dendritic spines have revealed that each signaling pathway is differently regulated across multiple spatiotemporal domains. The spatial pattern of signaling activity expands from a single spine to the nearby dendritic area, dendritic branch and the nucleus, regulating different cellular events at each spatial scale. Temporally, biochemical events are typically triggered by short Ca2+ pulses (~10–100 ms). However, these signals can then trigger activation of downstream protein cascades that can last from milliseconds to hours. Recent imaging studies provide many insights into the biochemical processes governing signaling events of molecular assemblies at different spatial localizations. Here, we highlight recent findings of signaling dynamics during synaptic plasticity and discuss their roles in long-term structural plasticity of dendritic spines.

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“…The selective loss of thin spines as a consequence of ethanol withdrawal, observed in the present study, is consistent with a model in which the spine volume and spine density changes regulate the anatomy and activity of the network between prosencephalic and mesencephalic areas. Indeed, whereas long-term potentiation (LTP) requires spine head enlargement (41), with recruitment of additional AMPA-type glutamate receptors (42,43), LTD is associated with spine loss (44), which, in turn, may be dependent upon actin turnover (44), thereby altering regulation of the actin cytoskeleton structure (45).…”

Section: Discussionmentioning

confidence: 99%

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats

Spiga

Talani

Mulas

et al. 2014

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

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Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence.A lcohol addiction is a major public health problem in the Western world. In the United States alone, about 15% of adults have an alcohol-related disorder at some point in their life, and alcohol abuse costs the economy over $220 billion per y in medical care and productivity loss (1). A general consensus has emerged on drug addiction as a substance-induced, aberrant form of neural plasticity (2, 3). The nucleus accumbens (Nacc) plays a central role in the neural circuits that are responsible for goal-directed behaviors (4, 5) and in addictive states. Its activity is heavily modulated by glutamate-(GLU) and dopamine-(DA) containing projections that originate in cortical and limbic regions and converge on a common postsynaptic target: the medium spiny neuron (MSN). Furthermore, DA modulates GLU inputs to Nacc neurons (6, 7), both by directly influencing synaptic transmission and by modulating voltage-dependent conductances (8). Accordingly, interactions between DA and GLU are involved in druginduced locomotor stimulation and addiction (9, 10) and may represent useful potential therapeutic targets (11,12). In the distal portion of the dendrites of MSNs a significant subpopulation of spines shows a particular synaptic architecture, called the "striatal microcircuit" or "synaptic triad" (13, 14), which is characterized by a double, discrete, and reciprocal interaction between DA and GLU aff...

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Forgetting Is Regulated via Musashi-Mediated Translational Control of the Arp2/3 Complex

Cited by 87 publications

References 47 publications

C. elegans positive olfactory associative memory is a molecularly conserved behavioral paradigm

C. elegans positive olfactory associative memory is a molecularly conserved behavioral paradigm

Plasticity of Spine Structure: Local Signaling, Translation and Cytoskeletal Reorganization

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats

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