scholarly journals Drosophila Graf regulates mushroom body β-axon extension and olfactory long-term memory

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sungdae Kim ◽  
Joohyung Kim ◽  
Sunyoung Park ◽  
Joong-Jean Park ◽  
Seungbok Lee
Keyword(s):  
Mushroom Body ◽  
Neuronal Development ◽  
Growth Factor Receptor ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Long Term Memory ◽  
Loss Of Function ◽  
Specific Expression ◽  
Term Memory

AbstractLoss-of-function mutations in the humanoligophrenin-1(OPHN1) gene cause intellectual disability, a prevailing neurodevelopmental condition. However, the role OPHN1 plays during neuronal development is not well understood. We investigated the role of theDrosophilaOPHN1 ortholog Graf in the development of the mushroom body (MB), a key brain structure for learning and memory in insects. We show that loss of Graf causes abnormal crossing of the MB β lobe over the brain midline during metamorphosis. This defect inGrafmutants is rescued by MB-specific expression of Graf and OPHN1. Furthermore, MB α/β neuron-specific RNA interference experiments and mosaic analyses indicate that Graf acts via a cell-autonomous mechanism. Consistent with the negative regulation of epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) signaling by Graf, activation of this pathway is required for the β-lobe midline-crossing phenotype ofGrafmutants. Finally,Grafmutants have impaired olfactory long-term memory. Our findings reveal a role for Graf in MB axon development and suggest potential neurodevelopmental functions of human OPHN1.

scholarly journals Increased abundance of nuclear HDAC4 impairs neuronal development and long-term memory

2021 ◽  
Author(s):  
Patrick Main ◽  
Wei Jun Tan ◽  
David Wheeler ◽  
Helen L Fitzsimons
Keyword(s):  
Subcellular Distribution ◽  
Mushroom Body ◽  
Neuronal Development ◽  
Eye Development ◽  
Critical Role ◽  
Long Term Memory ◽  
Term Memory ◽  
Neuronal Nuclei ◽  
Transcriptional Changes

AbstractDysregulation of the histone deacetylase HDAC4 is associated with both neurodevelopmental and neurodegenerative disorders, and a feature common to many of these disorders is impaired cognitive function. HDAC4 shuttles between the nucleus and cytoplasm in both vertebrates and invertebrates and alterations in the amounts of nuclear and/or cytoplasmic HDAC4 have been implicated in these diseases. In Drosophila, HDAC4 also plays a critical role in the regulation of memory however the mechanisms through which it acts are unknown. Nuclear and cytoplasmically-restricted HDAC4 mutants were expressed in the Drosophila brain to investigate a mechanistic link between HDAC4 subcellular distribution, transcriptional changes and neuronal dysfunction. Deficits in mushroom body morphogenesis, eye development and long-term memory correlated with increased abundance of nuclear HDAC4 but were associated with minimal transcriptional changes. Although HDAC4 sequesters MEF2 into punctate foci within neuronal nuclei, no alteration in MEF2 activity was observed on overexpression of HDAC4, and knockdown of MEF2 had no impact on long-term memory, indicating that HDAC4 is likely not acting through MEF2. Similarly, deletion of the MEF2 binding site also had no impact on HDAC4-induced impairments in eye development, however it did significantly reduce the mushroom body deficits, thus nuclear HDAC4 acts through MEF2 to disrupt mushroom body development. These data provide insight into the mechanisms through which dysregulation of HDAC4 subcellular distribution impairs neurological function and provides new avenues for further investigation.

scholarly journals Increased Abundance of Nuclear HDAC4 Impairs Neuronal Development and Long-Term Memory

2021 ◽  
Vol 14 ◽  
Author(s):  
Patrick Main ◽  
Wei Jun Tan ◽  
David Wheeler ◽  
Helen L. Fitzsimons
Keyword(s):  
Binding Site ◽  
Subcellular Distribution ◽  
Mushroom Body ◽  
Neuronal Development ◽  
Eye Development ◽  
Critical Role ◽  
Long Term Memory ◽  
Term Memory ◽  
Transcriptional Changes

Dysregulation of the histone deacetylase HDAC4 is associated with both neurodevelopmental and neurodegenerative disorders, and a feature common to many of these disorders is impaired cognitive function. HDAC4 shuttles between the nucleus and cytoplasm in both vertebrates and invertebrates and alterations in the amounts of nuclear and/or cytoplasmic HDAC4 have been implicated in these diseases. In Drosophila, HDAC4 also plays a critical role in the regulation of memory, however, the mechanisms through which it acts are unknown. Nuclear and cytoplasmically-restricted HDAC4 mutants were expressed in the Drosophila brain to investigate a mechanistic link between HDAC4 subcellular distribution, transcriptional changes and neuronal dysfunction. Deficits in mushroom body morphogenesis, eye development and long-term memory correlated with increased abundance of nuclear HDAC4 but were associated with minimal transcriptional changes. Although HDAC4 sequesters MEF2 into punctate foci within neuronal nuclei, no alteration in MEF2 activity was observed on overexpression of HDAC4, and knockdown of MEF2 had no impact on long-term memory, indicating that HDAC4 is likely not acting through MEF2. In support of this, mutation of the MEF2 binding site within HDAC4 also had no impact on nuclear HDAC4-induced impairments in long-term memory or eye development. In contrast, the defects in mushroom body morphogenesis were ameliorated by mutation of the MEF2 binding site, as well as by co-expression of MEF2 RNAi, thus nuclear HDAC4 acts through MEF2 to disrupt mushroom body development. These data provide insight into the mechanisms through which dysregulation of HDAC4 subcellular distribution impairs neurological function and provides new avenues for further investigation.

scholarly journals Upregulated energy metabolism in the Drosophila mushroom body is the trigger for long-term memory

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Pierre-Yves Plaçais ◽  
Éloïse de Tredern ◽  
Lisa Scheunemann ◽  
Séverine Trannoy ◽  
Valérie Goguel ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Mushroom Body ◽  
Long Term Memory ◽  
Term Memory

scholarly journals Long-term memory requires sequential protein synthesis in three subsets of mushroom body output neurons in Drosophila

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jie-Kai Wu ◽  
Chu-Yi Tai ◽  
Kuan-Lin Feng ◽  
Shiu-Ling Chen ◽  
Chun-Chao Chen ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mushroom Body ◽  
Long Term Memory ◽  
Term Memory ◽  
Output Neurons

scholarly journals Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation

2013 ◽  
Vol 110 (19) ◽  
pp. 7898-7903 ◽  
Author(s):  
T.-P. Pai ◽  
C.-C. Chen ◽  
H.-H. Lin ◽  
A.-L. Chin ◽  
J. S.-Y. Lai ◽  
...  
Keyword(s):  
Mushroom Body ◽  
Memory Formation ◽  
Long Term Memory ◽  
Term Memory ◽  
Output Neurons

scholarly journals Systematic functional characterization of the intellectual disability-associated SWI/SNF complex reveals distinct roles for the BAP and PBAP complexes in post-mitotic memory forming neurons of the Drosophila mushroom body

2018 ◽  
Author(s):  
Melissa C. Chubak ◽  
Max H. Stone ◽  
Nicholas Raun ◽  
Shelby L. Rice ◽  
Mohammed Sarikahya ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Mushroom Body ◽  
Functional Characterization ◽  
Long Term Memory ◽  
Term Memory ◽  
Functional Understanding ◽  
Short And Long Term ◽  
Cellular Components

AbstractTechnology has led to rapid progress in the identification of genes involved in neurodevelopmental disorders like intellectual disability (ID), but our functional understanding of the causative genes is lagging. Here, we show that the SWI/SNF chromatin remodeling complex is one of the most overrepresented cellular components disrupted in ID. We systematically investigated the role of individual subunits of this large protein complex in post-mitotic memory forming neurons of the Drosophila mushroom body (MB). Using this approach, we have identified novel differential roles for the two prominent conformations of the Drosophila SWI/SNF complex, known as BAP and PBAP. The PBAP conformation is required post-mitotically for remodeling of the MB γ neurons during morphogenesis and is essential for both short and long-term memory. In contrast, the BAP conformation appears to preferentially effect long-term memory and is associated with γ neuron survival. Our results suggest that different subunits of the SWI/SNF complex may influence learning and memory through diverse and distinct roles in regulating structural plasticity, survival, and functionality of post-mitotic neurons. This study provides novel insight into the neuronal function of individual SWI/SNF subunits and will serve as a basis for understanding SWI/SNF-mediated gene regulatory mechanisms in post-mitotic neurons.

scholarly journals Long-term memory is formed immediately without the need for protein synthesis-dependent consolidation in Drosophila

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Bohan Zhao ◽  
Jiameng Sun ◽  
Xuchen Zhang ◽  
Han Mo ◽  
Yijun Niu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mushroom Body ◽  
Brain Regions ◽  
Long Term Memory ◽  
Single Trial ◽  
Olfactory Conditioning ◽  
Consolidation Process ◽  
Independent Manner ◽  
Term Memory

Abstract It is believed that long-term memory (LTM) cannot be formed immediately because it must go through a protein synthesis-dependent consolidation process. However, the current study uses Drosophila aversive olfactory conditioning to show that such processes are dispensable for context-dependent LTM (cLTM). Single-trial conditioning yields cLTM that is formed immediately in a protein-synthesis independent manner and is sustained over 14 days without decay. Unlike retrieval of traditional LTM, which requires only the conditioned odour and is mediated by mushroom-body neurons, cLTM recall requires both the conditioned odour and reinstatement of the training-environmental context. It is mediated through lateral-horn neurons that connect to multiple sensory brain regions. The cLTM cannot be retrieved if synaptic transmission from any one of these centres is blocked, with effects similar to those of altered encoding context during retrieval. The present study provides strong evidence that long-term memory can be formed easily without the need for consolidation.

scholarly journals A Permissive Role of Mushroom Body α/β Core Neurons in Long-Term Memory Consolidation in Drosophila

2012 ◽  
Vol 22 (21) ◽  
pp. 1981-1989 ◽  
Author(s):  
Cheng Huang ◽  
Xingguo Zheng ◽  
Hong Zhao ◽  
Min Li ◽  
Pengzhi Wang ◽  
...  
Keyword(s):  
Memory Consolidation ◽  
Mushroom Body ◽  
Long Term Memory ◽  
Term Memory ◽  
Permissive Role
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