Forgetting and small G protein Rac

Shuai, Yichun; Zhong, Yi

doi:10.1007/s13238-010-0077-z

Cited by 9 publications

(4 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, forgetting of olfactory aversive memory in Drosophila depends on a particular set of intracellular molecular pathways within KCs, involving Rac, DAMB, and possibly others (25), and also receives modulation from extrinsic neurons. Although important cellular evidence supporting the hypothesis that memory traces are erased under these circumstances is still lacking, these findings lend support to the notion that forgetting is an active, biologically regulated process (17,26).Although existing studies point to the MB circuit as essential for forgetting, several questions remain to be answered. First, whereas the molecular pathways for learning and forgetting of olfactory aversive memory are distinct and separable (6, 7), the neural circuits seem to overlap.…”

mentioning

confidence: 66%

“…In Drosophila, single-session Pavlovian conditioning by pairing an odor (conditioned stimulus, CS) with electric shock (unconditioned stimulus, US) induces aversive memories that are short-lasting (16). The memory performance of fruit flies is observed to drop to a negligible level within 24 h, decaying rapidly early after training and slowing down thereafter (17). Memory decay or forgetting requires the activation of the small G protein Rac, a signaling protein involved in actin remodeling, in the mushroom body (MB) intrinsic neurons (6).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory

Shuai

Hirokawa

et al. 2015

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

Self Cite

View full text Add to dashboard Cite

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.forgetting | Drosophila melanogaster | associative memory | mushroom body | reversal learning A lthough forgetting commonly has a negative connotation, it is a functional process that shapes memory and cognition (1-4). Recent studies, including work in relatively simple invertebrate models, have started to reveal basic biological mechanisms underlying forgetting (5-15). In Drosophila, single-session Pavlovian conditioning by pairing an odor (conditioned stimulus, CS) with electric shock (unconditioned stimulus, US) induces aversive memories that are short-lasting (16). The memory performance of fruit flies is observed to drop to a negligible level within 24 h, decaying rapidly early after training and slowing down thereafter (17). Memory decay or forgetting requires the activation of the small G protein Rac, a signaling protein involved in actin remodeling, in the mushroom body (MB) intrinsic neurons (6). These so-called Kenyon cells (KCs) are the neurons that integrate CS-US information (18,19) and support aversive memory formation and retrieval (20)(21)(22). In addition to Rac, forgetting also requires the DAMB dopamine receptor (7), which has highly enriched expression in the MB (23). Evidence suggests that the dopamine-mediated forgetting signal is conveyed to the MB by dopamine neurons (DANs) in the protocerebral posterior lateral 1 (PPL1) cluster (7,24). Therefore, forgetting of olfactory aversive memory in Drosophila depends on a particular set of intracellular molecular pathways within KCs, involving Rac, DAMB, and possibly others (25), and also receives modulation from extrinsic neurons. Although important cellular evidence supporting the hypothesis that memory traces are erased under these circumstances is still lacking, these findings lend support to the notion that forgetting is an active, biologically regulated process (17,26).Although existing studies point to the MB circuit as essential for forgetting, several questions remain to be answered. Fir...

show abstract

mentioning

confidence: 66%

mentioning

confidence: 99%

Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory

Shuai

Hirokawa

et al. 2015

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the wild type situation (Figure 7, left panel), ongoing activity in DAn, regulated by the behavioral state (Berry et al, 2015), initiates the forgetting signal to the MBn by activating the Damb receptor, which in turn, deploys the forgetting signalosome and the activation of Rac1, Pak3 and the phosphorylation of Cofilin in the MBn. This signaling complex regulates actin dynamics and produces cytoskeletal changes that emerge as forgetting (Shuai and Zhong, 2010). Reducing Scrb function in MBn impairs the forgetting signal postsynaptically (Figure 7 middle panel), by altering the abundance and efficacy of the forgetting signaling complex.…”

Section: Discussionmentioning

confidence: 99%

Scribble Scaffolds a Signalosome for Active Forgetting

Cervantes-Sandoval

Chakraborty

MacMullen

et al. 2016

Neuron

102

View full text Add to dashboard Cite

SUMMARY Forgetting, one part of the brain’s memory management system, provides balance to the encoding and consolidation of new information by removing unused or unwanted memories or by suppressing their expression. Recent studies identified the small G-protein, Rac1, as a key player in the Drosophila mushroom bodies neurons (MBn) for, active forgetting. We subsequently discovered that a few dopaminergic neurons (DAn) that innervate the MBn mediate forgetting. Here we show that Scribble, a scaffolding protein known primarily for its role as a cell polarity determinant, orchestrates the intracellular signaling for normal forgetting. Knocking down scribble expression in either MBn or DAn impairs normal memory loss. Scribble interacts physically and genetically with Rac1, Pak3 and Cofilin within MBn, nucleating a forgetting signalosome that is downstream of dopaminergic inputs that regulate forgetting. These results bind disparate molecular players in active forgetting into a single signaling pathway: Dopamine→Dopamine Receptor→Scribble→Rac→Cofilin.

show abstract

“…Acquired memory that is not reinforced by repetitive learning is vulnerable to being erased or forgotten (Shuai and Zhong, 2010). A recent report showed that Rac1 contributes to both passive memory decay and forgetting in Drosophila (Shuai et al, 2010).…”

Section: Rho Family Gtpasesmentioning

confidence: 99%