A Normative Theory of Forgetting: Lessons from the Fruit Fly

Brea, Johanni; Urbanczik, Robert; Senn, Walter

doi:10.1371/journal.pcbi.1003640

Cited by 35 publications

(24 citation statements)

References 27 publications

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“…The ability to forget confers adaptive advantages to animals living in a changing environment (68,69); for example, memory inconsistent with the current circumstance needs to be quickly removed or suppressed, which otherwise may endanger one's survival. We here used a simple reversal learning paradigm (Fig.…”

Section: Resultsmentioning

confidence: 99%

Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory

Shuai

Hirokawa

et al. 2015

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

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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...

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Section: Resultsmentioning

confidence: 99%

Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory

Shuai

Hirokawa

et al. 2015

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

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“…The clearance of irrelevant memories would open new storage space and facilitate retrieval, making the brain more efficient for error-free retrieval (Rosenzweig et al, 2002). Moreover, it seems intuitive that some level of active forgetting would offer increased fitness by reducing recurring and unwanted situations or unrewarded perseveration (Kraemer and Golding, 1997; Storm, 2011; Brea et al, 2014). One strain of Drosophila named rovers explore their environment actively whereas an allelic variant, named sitters, are much more stationary.…”

Section: The Viewpoint Of Active Biological Forgetting Of Memory Tracesmentioning

confidence: 99%

The Biology of Forgetting—A Perspective

Davis

Zhong

2017

Neuron

246

268

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Pioneering research studies, beginning with those using Drosophila, have identified several molecular and cellular mechanisms for active forgetting. The currently known mechanisms for active forgetting include neurogenesis-based forgetting, interference-based forgetting, and intrinsic forgetting, the latter term describing the brain’s chronic signaling systems that function to slowly degrade molecular and cellular memory traces. The best-characterized pathway for intrinsic forgetting includes “forgetting cells” that release dopamine onto engram cells, mobilizing a signaling pathway that terminates in the activation of Rac1/cofilin to effect changes in the actin cytoskeleton and neuron/synapse structure. Intrinsic forgetting may be the default state of the brain, constantly promoting memory erasure and competing with processes that promote memory stability like consolidation. A better understanding of active forgetting will provide insights into the brain’s memory management system and human brain disorders that alter active forgetting mechanisms.

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“…Why we forget, has been an intriguing and central question in psychology and neuroscience for more than a century. Even though forgetting is often thought of as a failure or limitation of the brain, recent studies support the view that forgetting is a biologically regulated function of the brain allowing optimal adaptability to an ever-changing environment (Berry and Davis, 2014; Berry et al, 2012; Shuai et al, 2010; Brea et al, 2014). In the fruit fly Drosophila , we recently showed that the very same set of dopamine neurons (DANs) that signal through one receptor to form aversive olfactory memories, also signal through a separate receptor after learning to forget these memories (Berry et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Sleep Facilitates Memory by Blocking Dopamine Neuron-Mediated Forgetting

Berry

Cervantes-Sandoval

Chakraborty

et al. 2015

Cell

214

233

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SUMMARY Early studies from psychology suggest that sleep facilitates memory retention by stopping ongoing retroactive interference caused by mental activity or external sensory stimuli. Neuroscience research with animal models, on the other hand, suggests that sleep facilitates retention by enhancing memory consolidation. Recently in Drosophila, the ongoing activity of specific dopamine neurons was shown to regulate the forgetting of olfactory memories. Here we show this ongoing dopaminergic activity is modulated with behavioral state, increasing robustly with locomotor activity and decreasing with rest. Increasing sleep-drive, with either the sleep-promoting agent Gaboxadol or by genetic stimulation of the neural circuit for sleep, decreases ongoing dopaminergic activity, while enhancing memory retention. Conversely, increasing arousal stimulates ongoing dopaminergic activity and accelerates dopaminergic based forgetting. Therefore, forgetting is regulated by the behavioral state modulation of dopaminergic-based plasticity. Our findings integrate psychological and neuroscience research on sleep and forgetting.

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A Normative Theory of Forgetting: Lessons from the Fruit Fly

Cited by 35 publications

References 27 publications

Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory

Dissecting neural pathways for forgetting in Drosophila olfactory aversive memory

The Biology of Forgetting—A Perspective

Sleep Facilitates Memory by Blocking Dopamine Neuron-Mediated Forgetting

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