Serotonin–mushroom body circuit modulating the formation of anesthesia-resistant memory in
            <i>Drosophila</i>

Lee, Pei-Tseng; Lin, Hsuan-Wen; Chang, Yu‐Hsuan; Fu, Tsai‐Feng; Dubnau, Josh; Hirsh, Jay; Lee, Tzumin; Chiang, Ann‐Shyn

doi:10.1073/pnas.1019483108

Cited by 133 publications

(167 citation statements)

References 48 publications

Supporting

Mentioning

158

Contrasting

Order By: Relevance

“…A wealth of evidence suggests that aversive olfactory memory exists as a persistent neural activity ("trace") in a sparse subset of MB neurons-initially in the γ lobes lasting for several minutes and then spreading to α/β lobes for several hours (34)(35)(36). This physiological trace drives a protein-synthesis-dependent process in postsynaptic MB-V3 neurons, yielding structural change at MB::MB-V3 synapses (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.

Self Cite

120

135

View full text Add to dashboard Cite

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...

show abstract

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.

Self Cite

120

135

View full text Add to dashboard Cite

show abstract

“…Cantonized w 1118 [w(CS10)] or Canton-S flies of mixed sex were used as normal controls in our experiments. Flies carrying uas transgenes included uas-shi ts (Kitamoto, 2001) anduas-G-CaMP3.0 (Tian et al, 2009). Gal4 driver lines included c316-gal4, c739-gal4, and VT64246-gal4.…”

Section: Methodsmentioning

confidence: 99%

“…Functionally, the different MB neurons seem to participate in different aspects of memory processing, as revealed through behavioral studies, although this relationship is complex and not fully understood. Both the ␥ and ␣Ј/␤Ј neurons appear to have roles in early forms of memory, whereas the ␣/␤ MB neurons are involved in longer forms of memory and retrieval (Yu et al, 2006;Krashes et al, 2007;Wang et al, 2008;Akalal et al, 2011;Qin et al, 2012;Cervantes-Sandoval et al, 2013). Furthermore, memory traces with different temporal features, as revealed by functional cellular imaging, have been mapped to different classes of MB neurons (Yu et al, 2006;Wang et al, 2008;Akalal et al, 2010;.…”

Section: Introductionmentioning

confidence: 99%

“…Multiple cycle conditioning with no rest between each cycle (massed conditioning) generates robust initial memory that decays over a few days, whereas introducing a rest between cycles (spaced conditioning) generates memory that persists for 4 -7 d and is dependent on normal protein synthesis and the cAMP response element-binding protein (Creb) activity at the time of conditioning (Tully et al, 1994;Perazzona et al, 2004;Yu et al, 2006). Olfactory memories are thought to be stored in the mushroom body (MB) neurons McGuire et al, 2001;Krashes et al, 2007), a symmetrical structure that is composed of ϳ2500 neurons in each hemisphere and can be structurally dissected into the ␣/␤, ␣Ј/␤Ј, and ␥ neuron systems (Crittenden et al, 1998;Lee et al, 1999). Functionally, the different MB neurons seem to participate in different aspects of memory processing, as revealed through behavioral studies, although this relationship is complex and not fully understood.…”

Section: Introductionmentioning

confidence: 99%

“…For example, a single cycle of conditioning generates short-term memory that decays over the period of ϳ1 d (Tully et al, 1994;Beck et al, 2000;Pascual and Préat, 2001). Multiple cycle conditioning with no rest between each cycle (massed conditioning) generates robust initial memory that decays over a few days, whereas introducing a rest between cycles (spaced conditioning) generates memory that persists for 4 -7 d and is dependent on normal protein synthesis and the cAMP response element-binding protein (Creb) activity at the time of conditioning (Tully et al, 1994;Perazzona et al, 2004;Yu et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Aging Impairs Protein-Synthesis-Dependent Long-Term Memory inDrosophila

Tonoki

Davis

2015

J. Neurosci.

View full text Add to dashboard Cite

Although aging is known to impair intermediate-term memory in Drosophila, its effect on protein-synthesis-dependent long-term memory (LTM) is unknown. We show here that LTM is impaired with age, not due to functional defects in synaptic output of mushroom body (MB) neurons, but due to connectivity defects of dorsal paired medial (DPM) neurons with their postsynaptic MB neurons. GFP reconstitution across synaptic partners (GRASP) experiments revealed structural connectivity defects in aged animals of DPM neurons with MB axons in the ␣ lobe neuropil. As a consequence, a protein-synthesis-dependent LTM trace in the ␣/␤ MB neurons fails to form. Aging thus impairs protein-synthesis-dependent LTM along with the ␣/␤ MB neuron LTM trace by lessening the connectivity of DPM and ␣/␤ MB neurons.

show abstract

Localization of the Contacts Between Kenyon Cells and Aminergic Neurons in the Drosophila melanogaster Brain Using SplitGFP Reconstitution

Pech

Pooryasin

Birman

et al. 2013

J of Comparative Neurology

View full text Add to dashboard Cite

The mushroom body of the insect brain represents a neuronal circuit involved in the control of adaptive behavior, e.g., associative learning. Its function relies on the modulation of Kenyon cell activity or synaptic transmitter release by biogenic amines, e.g., octopamine, dopamine, or serotonin. Therefore, for a comprehensive understanding of the mushroom body, it is of interest not only to determine which modulatory neurons interact with Kenyon cells but also to pinpoint where exactly in the mushroom body they do so. To accomplish the latter, we made use of the GRASP technique and created transgenic Drosophila melanogaster that carry one part of a membrane-bound splitGFP in Kenyon cells, along with a cytosolic red fluorescent marker. The second part of the splitGFP is expressed in distinct neuronal populations using cell-specific Gal4 drivers. GFP is reconstituted only if these neurons interact with Kenyon cells in close proximity, which, in combination with two-photon microscopy, provides a very high spatial resolution. We characterize spatially and microstructurally distinct contact regions between Kenyon cells and dopaminergic, serotonergic, and octopaminergic/tyraminergic neurons in all subdivisions of the mushroom body. Subpopulations of dopaminergic neurons contact complementary lobe regions densely. Octopaminergic/tyraminergic neurons contact Kenyon cells sparsely and are restricted mainly to the calyx, the α'-lobes, and the γ-lobes. Contacts of Kenyon cells with serotonergic neurons are heterogeneously distributed over the entire mushroom body. In summary, the technique enables us to localize precisely a segmentation of the mushroom body by differential contacts with aminergic neurons.

show abstract

Serotonin–mushroom body circuit modulating the formation of anesthesia-resistant memory in Drosophila

Cited by 133 publications

References 48 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

Aging Impairs Protein-Synthesis-Dependent Long-Term Memory inDrosophila

Localization of the Contacts Between Kenyon Cells and Aminergic Neurons in the Drosophila melanogaster Brain Using SplitGFP Reconstitution

Contact Info

Product

Resources

About