Ilex kudingcha C.J. Tseng Mitigates Phenotypic Characteristics of Human Autism Spectrum Disorders in a Drosophila Melanogaster Rugose Mutant

Pham, Hang Thi Nguyet; Tran, Hong Nguyen; Le, Xoan Thi; Hà, Thị Liên; Nguyen, Tue Trong; Nguyen, Chien Le; Yoshida, Hideki; Yamaguchi, Masamitsu; William, Folk R; Matsumoto, Kinzo

doi:10.1007/s11064-021-03337-7

Cited by 5 publications

(1 citation statement)

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“…Moreover, GABAergic anterior paired lateral (APL) neurons broadly control MB activity through feedback to the KCs, and are most strongly activated by the α’/β’ lobes ( Liu and Davis, 2009 ; Lin et al, 2014 ; Inada et al, 2017 ; Modi et al, 2020 ). Recent work shows that treatment with a dopamine transport inhibitor also ameliorates rg mutant social interaction and memory deficits ( Pham et al, 2021 ). Another candidate is the Amnesiac neuropeptide from the serotonergic dorsal paired medial neurons, required for their normal development in the broad innervation of the MB lobes ( Yu et al, 2005 ; Lee et al, 2011 ; Turrel et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Temporally and Spatially Localized PKA Activity within Learning and Memory Circuitry Regulated by Network Feedback

Sears

Broadie

2022

eNeuro

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Dynamic functional connectivity within brain circuits requires coordination of intercellular signaling and intracellular signal transduction. Critical roles for cAMP-dependent protein kinase A (PKA) signaling are well established in the Drosophila mushroom body (MB) learning and memory circuitry, but local PKA activity within this well-mapped neuronal network is uncharacterized. Here, we use an in vivo PKA activity sensor (PKA-SPARK) to test spatiotemporal regulatory requirements in the MB axon lobes. We find immature animals have little detectable PKA activity, whereas postcritical period adults show high field-selective activation primarily in just 3/16 defined output regions. In addition to the age-dependent PKA activity in distinct α’/β’ lobe nodes, females show sex-dependent elevation compared with males in these same restricted regions. Loss of neural cell body Fragile X mental retardation protein (FMRP) and Rugose [human Neurobeachin (NBEA)] suppresses localized PKA activity, whereas overexpression (OE) of MB lobe PKA-synergist Meng-Po (human SBK1) promotes PKA activity. Elevated Meng-Po subverts the PKA age-dependence, with elevated activity in immature animals, and spatial-restriction, with striking γ lobe activity. Testing circuit signaling requirements with temperature-sensitive shibire (human Dynamin) blockade, we find broadly expanded PKA activity within the MB lobes. Using transgenic tetanus toxin to block MB synaptic output, we find greatly heightened PKA activity in virtually all MB lobe fields, although the age-dependence is maintained. We conclude spatiotemporally restricted PKA activity signaling within this well-mapped learning/memory circuit is age-dependent and sex-dependent, driven by FMRP-Rugose pathway activation, temporally promoted by Meng-Po kinase function, and restricted by output neurotransmission providing network feedback.

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